Advisory Committee on Dangerous Pathogens
Categorisation of biological agents according to hazard and categories of containment
Fourth edition 1995
HSE BOOKS ......
© Crown copyright 1995 Applications for reproduction should be made to HMSO First published 1995
ISBN 0 7176 1038 1
This guidance is prepared in consultation with HSE, by the Advisory Committee on Dangerous Pathogens, which was appointed by the Health and Safety Commission as part of its formal advisory structure and by Health Ministers. The guidance represents what is considered to be good practice by members of the Committee. It has been agreed by the Commission and Health Ministers. Following the guidance is not compulsory and you are free to take other action but if you do follow it you will normally be doing enough to comply with the law. Health and safety inspectors seek to secure compliance with the law and may refer to this guidance as illustrating good practice.
As well as guidance this publication includes an Approved List of biological agents and extracts from the law.
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Foreword v
The Advisory Committee on Dangerous Pathogens vi
Introduction 1 COSHH and the Biological Agents Directive 1 The Classification Directive 1 Managing health and safety 2 Purpose of this guidance 4
Biological Agents 5 The hazards of biological agents 6 Newly discovered agents 7 Classification/categorisation and notification 7 Sensitisation and microbial toxicity 8 lmmunisation 8
Categorisation of biological agents 9 The Approved List - background 9 Guidance List - background 9 Nomenclature 9 Synonyms 9 Use of ‘spp’ 9 Zoonotic agents 9 References and sources of advice 10 Application of derogation to certain Hazard Group 3 agents - exemption certificate 10 Categorisation of biological agents - notations used 10 Definitions of hazard groups 11
Guidance List of biological agents 12
Containment 25 Hazard, risk and containment 25 Selection of containment levels 29
Laboratory Containment Level 1 31
Laboratory Containment Level 2 33
Laboratory Containment Level 3 36 Achieving an inward flow of air 39
Laboratory Containment Level 4 41
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AnimalContainment 45 Definition of terms 45
AnimalContainmentLevel1 46
AnimalContainmentLevel248
AnimalContainmentLevel351
AnimalContainmentLevel455
Appendices 1 Information, instruction and training 62 2 Supplementary containment measures for agents in Group 2 64 3 Working with parasites 65 4 Work with rabies virus 66 5 The containment of invertebrates 67 6 The large-scale use of biological agents 70 7 lmmunisation 80 8 Microbiological safety cabinets 82 9 Fumigation 87 10 Respiratory protective equipment 90 11 Safe disposal of clinical waste 91 12 Consignment of infectious material by post 94 13 The hazards of cell cultures 95 14 Persistent infections in animals 98 15 Genetically modified organisms and biological agents 102 16 Blood-borne viruses 104 17 Mycobacteria 108 18 Poxviruses 110 19 Transmissible spongiform encephalopathies 113 20 Pathogens controlled by the Agriculture and Fisheries Departments 116 21 Reporting occupational injuries, disease and dangerous occurrences 129 22 Notification of first use of biological agents; consignment of agents in Part V Schedule 9 of COSHH; provision of diagnostic services concerning agents in Part V 131 23 Approved List of biological agents 134
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Foreword by the Health and Safety Commission and Health Departments
The first edition of the now familiar categorisation of pathogens from the ACDP appeared early in 1984 and following thorough review, a revision was published in 1990. Those publications set and helped maintain new practical standards for the safe conduct of laboratory work with infectious agents. Both editions had the status of guidance supporting the Health and Safety at Work Act and more lately the Control of Substances Hazardous to Health Regulations 1988 (COSHH).
This further edition however, reflects the need to implement two European Community Directives concerned with biological agents and therefore marks a departure, in part, from guidance into law. New COSHH regulations (COSHH 1994), which came into force in January 1995, implement the first of these Directives (90/679/EEC) and include now mandatory control measures for laboratories. These are reproduced here.
The second Directive (93/88/EEC) contained a European Community classification of biological agents capable of causing infection. With permissible forms of modification, the Community classification appears here as an Approved List of biological agents which is specifically invoked by the new COSHH regulations and therefore also has legal status.
Although still aimed primarily at workplaces where biological agents are handled intentionally ie in diagnostic laboratories, research and industry, this new edition of the categorisation is a useful source of information for a number of other situations. For example, workers in clinical and biomedical laboratories not necessarily involved in the propagation of biological agents, will find it an essential supplement to their main source of guidance which comes from the Health Services Advisory Committee (see Bibliography).The guidance and information in the now extended list of appendixes may be helpful as these cover a number of topics not all of which are specifically addressed in any other single publication. In fact, it is appropriate for all types of laboratory where any potentially infectious material is handled to refer to both of these publications.
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THE ADVISORY COMMITTEE ON DANGEROUS PATHOGENS
The Advisory Committee on Dangerous Pathogens (ACDP) is an advisory committee of the Health and Safety Commission and also advises Health and Agriculture Ministers.
The ACDP was set up in 1981 following a second outbreak (resulting in a third death) of laboratory-acquired smallpox and was the successor to the Dangerous Pathogens Advisory Group. The Committee has an independent chairman and a joint secretariat provided by the Department of Health and the Health and Safety Executive.
There are eight expert members chosen from names put forward by professional bodies, four representatives of employees and four of employers (see overleaf). In addition, the committee is attended by observers from HSE, the Department of Health, the Ministry of Agriculture, Fisheries and Food, the Ministry of Defence and government departments in Scotland, Wales and Northern Ireland.
The terms of reference of the ACDP were changed in 1991 and are now:
To advise the Health and Safety Commission, the Health and Safety Executive and Health and Agriculture Ministers, as required, on all aspects of hazards and risks to workers and others from exposure to pathogens.
Committee membership is widely representative of expertise and long experience in most aspects of microbiology and infectious diseases in both the public sector and industry. Working Groups set up to deal with specific tasks commonly include other experts co-opted for their specialist knowledge of the topic to be addressed.
Advice and information on all matters relevant to the work of the Advisory Committee may be obtained from the Committee Secretariat at:
Department of Health or Health and Safety Executive HEF1 HPDB1 Skipton House Rose Court 81, London Road 2, Southwark Bridge London SE1 6LW London SE1 9HS
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Membership of the ACDP 1991 to 19941
Chairman: Dr M J Crumpton B Sc PhD CBE FRS Imperial Cancer Research Technology London
Expert members: Dr B Bannister MSc FRCP MRCS Royal Free and Coppett’s Wood Hospitals London (from November 1992)
Dr C J Bostock BSc PhD Institute of Animal Health Compton Berks (until 1993)
Dr G J Boulnois BSc PhD University of Leicester and then ICI (until 1993)
Mr A Cremer MlBiol CBiol FIMLS MRSH University College and Middlesex Hospitals London
Prof B I Duerden BSc MB BCh MRCPath MD University of Wales College of Medicine and Public Health Laboratory Cardiff
Dr R J Fallon BSc MD MB BCh FRCP FRCPath formerly of Ruchill Hospital Glasgow
Prof D J Jeffries BSc MB BS FRCPath St Bartholomew’s Hospital London (from 1993)
Prof E R Moxon MB BChir FRCP John Radcliffe Hospital Oxford (until August 1992)
Dr S Young BA MB BCh DCH Dip Bact FFCMI FRCP PHLS CDSC (until February 1992)
Dr T D Wyatt BSc PhD Mater lnfirmorum Hospital Belfast
1 The membership listed here is that which was current at the time that work on the text of this publication was completed. The membership of the ACDP was reconstituted in January 1995.
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Employee representatives Employer representatives
MS J Church BA Mr A R Clare BTech MlBiol MSF representative CBI representative
Mrs R Conn SRN OHN Cert Dr E A Gould PhD RCN representative Research Councils representative
Mr K Hargreaves FIMLS MS A Harris BSc FIMLS UNISON representative CBI representative
Dr R Owen OBE MB ChB FFOM Mr E A Meyrick FIMLS DMJ DIH LRSC PHLS/NHS representative (until 1993) TUC representative Mrs V Bevan MSc FIBMS Cert MHS MHSM PHLS/NHS representative (from May 1994)
Observers
Dr H Campbell DHSS N Ireland Mr K Dale MAFF
Mr A Fleetwood MAFF Dr D Harper Dept of Health
Dr A Keel Scottish Office Mrs R LeGuen HSE
Mr J Newbold HSE Dr H Nicholas Dept of Health
Dr E Parry CBDE MoD Mr D Redwood MAFF
Mr N Rigby HSE Dr R Salmon Welsh Off ice
Mr D Sweasey MAFF (until 1993)
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INTRODUCTION
COSHH and the 1 Since the second edition of the categorisation of pathogens1 was published Biological Agents early in 1990, the Council of Ministers of the European Community (now the Directives European Union) has adopted two Directives concerned with biological agents The first of these, the Biological Agents Directive 90/679/EEC2, was implemented in domestic law in the United Kingdom in the new Control of Substances Hazardous to Health Regulations (COSHH) 19943. Unlike COSHH 1988, the new Regulations now specify the control measures to be applied in all occupations for preventing or minimising the risk of illness associated with exposure to biological agents at work.
2 As a result of this Directive, the definition of a biological agent used in COSHH 1994 is:
‘any micro-organism, cell culture or human endoparasite, including any which have been genetically modified, which may cause any infection, allergy, toxicity or otherwise create a hazard to human health’.
3 Although the requirements have always been implicit in sections 2 and 3 of the Health and Safety at Work etc Act of 1974 (HSWA), since 1988, COSHH has specifically stipulated the need to carry out an assessment of risks and to select and maintain appropriate control measures where there is perceived to be exposure to any ‘...micro-organism which may be a hazard to the health of any person..‘. Previous editions of this publication provided some of the necessary guidance for those controls to be set in place in laboratories and for experimental work with infected animals. This new edition (now a categorisation of biological agents in conformity with the European Directives - see also paragraph 4) reiterates those parts of the Regulations that concern the containment measures to be used in laboratories and animal rooms and in the industrial use of biological agents. These have legal status and are highlighted by shading in the text at the various levels of containment to distinguish them from other features of containment and control that remain as guidance as before.
The Classification 4 A second Directive (93/88/EEC), providing a Community classification of Directive biological agents, was adopted in October 1993. This contains the numerous species of bacteria, viruses, fungi and parasites known to be capable of causing infection in people not compromised by pre-existing disease, medication or pregnancy. The new categorisation appearing here, which is based closely on the Classification Directive (recently amended by the European Commission through technical adjustment procedures), has the status of law as it is an ‘Approved List’ made under Section 15 of the HSWA (see paragraph 30). Infectious agents are
1 An interim third edition of the categorisation containing an Approved List of biological agents was issued in January 1995 coincident with the emergence of the new COSHH Regulations. Since then, there has been formal technical adjustment of the classification Directive (see paragraph 3). The Approved List in this fourth edition of the categorisation incorporates the changes made to that Directive. 2 EC Directive 90/679/EEC on the protection of workers from risks related to exposure to biological agents at work. 3 The Control of Substances Hazardous to Health Regulations 1994No 3246 ISBN 0 11 043721 7.
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categorised in numbered hazard groups according to definitions which are effectively identical to those adopted by the ACDP in 1984.
5 Genetically modified micro-organisms (‘GMMOs’ - bacteria, viruses, fungi and parasites), although included in the definition of a biological agent, have not been categorised in the Approved List as it is not practical to do so, there being so many variants of so many different species. GMMOs that have any harmful properties for humans are subject to the controls demanded by COSHH, including, for example those concerning laboratory containment. But other regulations also apply and extensive guidance dealing specifically with genetic modification has been published elsewhere 1.
6 Cell cultures are also biological agents according to the definition but they are not classified as the classification is based solely on disease caused by infection. However, as cell cultures may present other hazards, these must be taken into account in complying with COSHH. Appendix 13 provides guidance on work with cell cultures. Therefore, except where the text is otherwise explicit, reference here to ‘biological agents’ or simply ‘agent’ means wild-type micro- organisms (which includes bacteria, viruses and fungi) and endoparasites.
Managing health LEGlSLATION and safety The Health and Safety at Work etc Act 1974
7 The Health and Safety at Work Act places responsibilities on employers and employees much wider than those that relate strictly to biological hazards. Local rules (see paragraph 54) should therefore take account of the general duties in the Act as well as other more specific legislation and Approved Codes of Practice associated with it. Examples include those statutory controls concerned with radioactive substances and toxic and dangerous chemicals, compressed gases, the special needs of vulnerable workers, fire precautions and the general management of health and safety at work.
COSHH 1994
8 Good management of health and safety is a matter of adopting a systematic approach comparable to that applicable to any other aspect of management. COSHH and other similar legislation, backed by appropriate guidance, provides a framework for achieving this. Risk assessment and the various other duties described in COSHH 1988 remain in the new Regulations, but there are now considerably more details on control measures for work with biological agents, including some new requirements which stem directly from the Biological Agents Directive.
1 See A guide to the Genetically Modified Organisms (Contained Use) Regulations 1992 ISBN 0 11 882049 4 and HSE/ACGM Compendium of guidance.
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9 The elements of COSHH 1994 as they relate to work with biological agents are: (a) risk assessment;
(b) prevention of exposure or substitution of an agent with one that is less hazardous (where the nature of the activity permits);
(c) selection of control measures;
(d) maintenance, examination and test of control measures including, for example, protective equipment such as safety cabinets;
(e) provision of information, instruction and training for employees;
(f) keeping a list of employees exposed to agents in Group 3 and Group 4;
(g) notification of ‘first use’ of biological agents in Groups 2, 3 and 4;
(h) notification of the consignment or importation of biological agents listed in Part V of Schedule 9 of COSHH;
(i) monitoring exposure at the workplace (if there is a suitable procedure);
(j) health surveillance of employees (where it is appropriate and if there are valid techniques for detecting indications of disease) when it can lead to action that will be of benefit to the health of employees.
The Management of Health and Safety at Work Regulations 1992
10 The requirements of the Management of Health and Safety at Work Regulations (MHSWR) 1992, because of their wide-ranging nature, overlap with other health and safety legislation, including COSHH. Where this occurs, compliance with the duty in the more specific regulations will normally be sufficient to meet the corresponding requirement of MHSWR. For example, COSHH requires employers and the self-employed to assess risks arising from substances hazardous to health including, in this context, those that present a risk of infection, allergy or illness caused by microbial toxins. Similarly, a detailed assessment is required to comply with the Genetically Modified Organisms (Contained Use) Regulations 1992 (‘the GM Regulations’). But the assessment prepared for COSHH or for the GM Regulations will not need to be repeated for the purposes of the MHSWR although other issues may have to be considered. Other instances of overlap between the various sets of regulations include the appointment of personnel to carry out specific tasks or to make arrangements for dealing with emergencies. Where the duties laid down in MHSWR go beyond those in the more specific regulations such as COSHH, the more stringent requirement must be met. For example, a recent
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amendment of MHSWR1 has been made to implement a Directive aimed at protecting pregnant and breastfeeding women at work.
The Genetically Modified Organisms (Contained Use) Regulations 1992
11 As indicated in paragraph 5, some genetically modified organisms are within the definition of a biological agent being either micro-organisms, cell cultures or endoparasites. While they are subject to control under the COSHH Regulations, other more specific requirements (for example for risk assessment and notification) also apply and reference must be made to the GM Regulations. Dual notification of intended work with GMMOs (ie under both COSHH and the Contained Use Regulations) is not required.
The Reporting of Injuries, Diseases and Dangerous Occurrences Regulations 1985
12 These Regulations aim to provide a national record of specified injuries, diseases and dangerous occurrences affecting people at work. A summary of the terms of the Regulations as they relate to infections and the reporting procedure is in Appendix 21.
The Carriage of Dangerous Substances by Road and Rail (Classification, Packaging and Labeling) Regulations 1994
13 New Regulations, concerning the packaging and labelling of goods for carriage by road and rail, are now in force.
The Health and Safety (Dangerous Pathogens) Regulations 1981
14 These Regulations, which dealt with notification of work with and consignment of certain scheduled pathogens, have been revoked in favour of the new system of notification set up in COSHH 1994 to conform with the Biological Agents Directive (see paragraph 25 onwards).
Purpose of 15 The now statutory measures for containment in COSHH and the guidance this guidance provided here relate, in the main, to work where the identity of an infectious biological agent is known and where there is an intention to manipulate it, propagate it or store it. The guidance is directed at all organisations where such work is carried out for whatever purpose but there are sections that are relevant to disciplines other than microbiology. Some laboratories may deal with specimens or other materials not intended for cultivation but which may nevertheless contain biological agents in sufficient concentration for a risk of infection to arise.
16 Specific guidance for work with clinical specimens, for example, has not been provided here. The Health Services Advisory Committee (HSAC) has published detailed recommendations for procedures suitable for clinical pathology
1 See Management of Health and Safety at Work (Amendment) Regulations 1994 SI 2865 HMSO ISBN 0 11 043021 2
...... Page 4 Advisory Committee on Dangerous Pathogens ...... laboratories and post-mortem examinations 1,2. The principles in that guidance are commended to anyone dealing with any materials that may be infectious for humans. In addition, the ACDP has published elsewhere detailed guidance on blood-borne viruses3 and for work with the human and animal transmissible 4 spongiform encephalopathies . Guidance on clinical laboratory procedures in connection with viral haemorrhagic fevers (Appendix E in the 1990 categorisation of pathogens) is under review and may be revised for publication in a new edition of the Memorandum on the control of viral haemorrhagic fevers 1986 (DHSS and Welsh Office ISBN 0 11 321049 3).
17 All employers whose work involves exposure of their employees to infection will need to refer to the Approved List of biological agents to be able to comply with the new COSHH Regulations and as the original appendices have been reviewed and revised and a number of new ones have been added, there is a significant body of useful information on which all can draw.
BIOLOGICAL AGENTS
18 Of necessity, the new categorisation of biological agents appearing in this publication closely reflects the classification Directive 93/88/EEC. Adoption of European Directives by the Council of Ministers of the European Union means that Member States are obliged to implement the provisions they contain in domestic legislation. Consequently, early in 1994, the HSE acting on behalf of the Health and Safety Commission conducted an extensive public consultation on a proposal to implement the classification by use of an Approved List (made under Section 15 of the HSWA) which is now specifically invoked by COSHH and thereby has legal status5. The same consultation proposed raising the minimum standards set by the Directive which is permissible under the Treaty base on which it was devised. In effect, this simply meant reinstating certain agents in the higher Hazard Group to which they had been allocated by the ACDP since at least 1990. At the same time, some agents have been relegated to a lower group in line with the Community classification. Furthermore, some agents now appear in a higher group than before as a result of the Directive although in many cases, the burden that this might impose has been relieved by formal derogation (see paragraph 19 and paragraph 38 onwards). Still other agents have been added, including a number that had not been listed before because they were unknown at the time or because their pathogenicity for healthy persons had not been recognised. Some agents have been deleted altogether from the categorisation published in 1990 in the light of improved knowledge.
1 See Safety in health service laboratories: Safe working and the prevention of infection in clinical laboratories. Health and Safety Commission, Health Services Advisory Committee 1991 ISBN 0 11 885446 1. 2 See Safety in health service laboratories: Safe working and the prevention of infection in the mortuary and post-mortem room Health and Safety Commission, Health Services Advisory Committee 1991 ISBN 0 11 885448 8. 3 See Protection against blood-borne infections at work - HIV and hepatitis. ACDP 1995 ISBN 0 11 321953 9. 4 See Precautions for work with the human animal transmissible spongiform encephalopathies ACDP 1994 HMSO ISBN 0 11 321805 2. 5 ‘Approved’ in this context means approved by the Health and Safety Commission for the purpose of Schedule 9 of the Control of Substances Hazardous to Health Regulations 1994...... Page 5 Advisory Committee on Dangerous Pathogens ......
19 As indicated, the classification Directive has placed a number of agents in a higher Hazard Group than before. As both the Biological Agents Directive and the classification Directive contain minimum standards, Member States are not at liberty to allocate any agent to a group lower than that in which it appears in the Directive. However, with some agents in Group 3, there is the facility for government authorities to allow use of less stringent levels of containment than is strictly indicated by the hazard grouping. This may be applied only to certain specified agents selected because there is deemed to be a low probability of their transmission by the airborne route. This principle of ‘derogation’ has been an important feature of the ACDP categorisation in the past where, for example guidance has indicated that use of a safety cabinet is not essential for work with certain parasites and enteric pathogens. Where this allowance is permissible, within the terms of the classification Directive, it has been carried forward selectively in the new categorisation (see paragraph 39 onward and the certificate of exemption in Appendix 23).
The hazards of 20 As before, biological agents have been categorised into four Hazard biological agents Groups using a framework of criteria which includes the following questions.
(a) Is the agent pathogenic for humans?
(b) Is it a hazard to employees?
(c) Is it transmissible to the community?
(d) Is effective prophylaxis or treatment available?
21 Using definitions based on these factors, biological agents known to cause infection have been assigned to one of the three higher Hazard Groups (see paragraph 44) but the lists are not exhaustive. Moreover, it must be emphasised that the categorisation does not allow for any additional risk for those people who may be more severely affected due to compromising factors. These include, for example:
(a) pre-existing disease;
(b) compromised immunity;
(c) the effects of medication;
(d) pregnancy.
When necessary, the assessment of risk should consider these additional factors as individual protective measures may be required. For example, the Management of Health and Safety at Work Regulations have recently been amended to implement control measures that may be applicable, subject to the assessment of risk in individual cases, to pregnant and breastfeeding women at work (see footnote on page 4).
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Newly discovered 22 From time to time, ‘new’ infectious agents are identified and some familiar agents organisms are shown to have previously unrecognised pathogenic properties. These new hazards will generally be signalled by adding the names of the agents concerned to the Approved List when any revision is published either as a result of review by the ACDP or through the technical adjustment procedures that can be applied to Directives by the European Commission. In some cases, attention may be drawn to particularly significant new findings and a hazard grouping proposed in separate guidance provided by the ACDP. Failing this, employers are required by COSHH to classify any unlisted or newly discovered agents and in certain cases inform HSE through formal notification procedures (see paragraph 23).
CLASSIFICATION OF UNLISTED AGENTS
Classification/ 23 Employers whose work involves keeping or handling agents not appearing categorisation and in the categorisation are required to allocate them to a Hazard Group notification provisionally in accordance with the definitions in paragraph 3(4) of Schedule 9 of COSHH. These definitions are reproduced in paragraph 44 below. In deciding which Hazard Group is appropriate, classification/categorisation will need to be based on all available information about the agent. If in doubt as to which group is appropriate, the higher of the two alternative groups in which it might be placed must be selected. The new Regulations demand that all viruses isolated from humans are allocated to Group 2 as a minimum, unless there is clear evidence to show that they are not pathogenic.
24 Where this provisional classification results in placing an agent in Hazard Group 3 or Hazard Group 4, there is a statutory requirement to notify HSE (see below and paragraph 12 of Schedule 9 in the COSHH Regulations 1994).
NOTIFICATION OF FIRST USE OF AGENTS IN GROUPS 2, 3 AND 4.
25 The new COSHH Regulations also call for notification at least 30 days in advance of ‘first use’ of biological agents in Groups 2, 3 or 4. Guidance on the precise meaning of ‘first use’ and an explanation of where notification does and does not apply are given in the Approved Code of Practice on biological agents1 and in Appendix 22. Briefly, notification is not necessary unless there is an intention to propagate, concentrate or store biological agents (but see paragraph 27 concerning all diagnostic work in connection with agents in Part V of Schedule 9). Therefore, a clinical chemistry department, for example, will normally not need to notify although specimens received will often contain infectious agents. Moreover, a blanket notification (for example ‘..all agents in Group(s).....‘) would be sufficient for say a new clinical microbiology laboratory or a research unit where the range of agents that might be encountered is unpredictable. It should be noted that the requirement to notify does not apply retrospectively, ie to work commenced before COSHH 1994 came into force in January 1995. This means that laboratories already handling biological agents
1 See Control of Substances Hazardous to Health Regulations 1994, Approved Codes of Practice, 1995...... ISBN 0 7176 0819 0. Page 7 Advisory Committee on Dangerous Pathogens ......
at that time need not notify unless their work has always been confined to agents in one or other of these three groups and new work is planned (see paragraph 26).
USE OF AGENTS NOT PREVIOUSLY NOTIFIED
26 Notification is required of the subsequent use or storage of any agents not covered by a previous notification including those provisionally classified in Group 3 by an employer (ie because they do not appear in the Approved List) and subsequent use or storage of any agent in Part V of Schedule 9 in the COSHH Regulations that has not been previously notified. This will also include agents provisionally classified by an employer in Group 4 as Part V of the Schedule is not specific in referring to ‘all agents in Group 4’ which means all such agents whether or not they appear in the Approved List at the time.
PART V NOTIFICATIONS
27 Where notification concerns work with, storage of, consignment of or importation of any of the agents in Part V of Schedule 9 in COSHH {some of which are in Hazard Group 3 - see Appendix 22), the new Regulations replace the former requirement to notify the HSE under the Health and Safety (Dangerous Pathogens) Regulations 1981. As before, notification is required at least 30 days in advance from laboratories intending to provide a diagnostic and clinical support service (ie haematology, clinical chemistry, bacteriology) in connection with patients who are or may be infected with agents in Part V whether or not the work will involve any attempt to cultivate the agent in question.
A form (CBA1) covering all aspects of notification and providing guidance is available from the ACDP Secretariat at HSE’s London Headquarters’.
Sensitisation and 28 There are indications in the new categorisation of which agents are known microbial toxicity to be respiratory sensitisers (‘A’ ) or are potentially toxigenic (‘T’) but use of these notations is not exhaustive. In determining the appropriate measures to prevent or reduce the risk of infection from agents so marked or others not marked in this way or even those not listed at all, it is necessary also to consider these other hazards to comply with the COSHH Regulations. A number of agents that would fall into Hazard Group 1 according to the definition (see paragraph 44) and are consequently not specified in the Approved List are also capable of inducing sensitisation. Some prominent examples are some normally non-pathogenic fungi such as various species of Penicillium and Aspergillus and the thermoactinomycetes responsible for Farmer’s Lung.
lmmunisation 29 The Approved List also contains indications (‘V’) of where an effective vaccine is known to be available. Further guidance on immunisation is provided in Appendix 7.
1 Health and Safety Executive, Health Policy Division B1, Room 703, 2, Southwark Bridge, London SE1 9HS.
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CATEGORISATION OF BIOLOGICAL AGENTS
The Approved List 30 The formal Approved List of biological agents implementing Directive - background 93/88/EEC along with the Notice of Approval and the certificate of exemption {see paragraph 39 onwards) is at Appendix 23. Here, each class of agent ( bacteria, viruses, fungi and parasites ) in Groups 2, 3 and 4 is simply arranged in alphabetical order which provides a quick reference to the hazard grouping of any particular agent.
Guidance List 31 To meet day-to-day needs for details concerning recommended - background supplementary containment measures, the application of the derogation permitted by the classification Directive and specific references to guidance etc, the same categorisation has been presented on pages 12 to 23 in a different format. This is arranged so that, for each class of agent, the most hazardous agents are listed first. Reference must be made to one or other of these two lists before selecting the minimum level of containment for the work proposed.
32 In both cases, only agents in Hazard Groups 2, 3 and 4 are listed and it should not be assumed that an unlisted agent is automatically in Group 1 if it does not appear in any of these higher groups.
Nomenclature 33 In general, the nomenclature used in the Approved List is that which conforms with the latest agreed taxonomy. However, to ensure that certain agents whose names may have changed only in the recent past are readily recognised, more familiar names and synonyms have also been retained. Some organisms formerly in the genus Pseudomonas, for example, are now in the genus Burkholderia.
Synonyms 34 Some agents have one or more synonyms in regular use. Before assuming that an unlisted agent is categorised in Hazard Group 1, the person responsible for the work must verify that its name is not synonymous with an agent in the lists.
Use of ‘spp’ 35 Where there are numerous species or subtypes in a genus, it is impractical to list them all. The most prominent agent(s) in a genus are specified and where necessary, there is an additional, more general entry, for example, ‘Clostridium spp’. This indicates that at least some other species in the genus are known to be pathogenic for humans. It should not be assumed automatically that any organism not specified is a non-pathogen nor that use of ‘spp’ means that every single species in a genus is capable of causing disease,
Zoonotic agents 36 Zoonotic agents are included in the categorisation solely on the basis of their hazard to humans. Other animal pathogens and pathogens of poultry, fish and bees are not listed but it should be noted that some of these can cause serious epizootics and work must be contained safely. Advice on the legislation controlling the pathogens of animals, poultry, fish, bees and plants may be obtained from the Agriculture Departments. Appendix 20 lists controlled pathogens and also provides contact addresses.
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References and 37 To assist with the classification of unlisted agents and for further sources of advice information on the pathogenic potential of those that are listed, references to some standard texts are provided in the bibliography at the end of this publication. In cases of doubt, the ACDP Secretariat may be able to offer help or provide the names of expert advisers if required.
Application of 38 COSHH at paragraph 8.4 in Schedule 9 stipulates that the minimum derogation to certain Containment Level to be used is that which matches the hazard grouping of the Hazard Group 3 agents agent in question. However, a formal derogation has been applied to specified - exemption certificate agents in Hazard Group 3 in the classification Directive where the risk of airborne transmission is deemed to be low. This allows HSE, as the competent authority in Great Britain, to permit the use of less stringent standards of containment for some types of work with those agents.
39 Where, on the advice of the ACDP, this option has been taken up, HSE has made use of an exemption certificate made under Regulation 14 of COSHH (see Appendix 23). Subject to their observing the conditions in paragraph 2 of the certificate, the exemptions are applicable to all employers whose work concerns any of the agents in the Schedule, ie no individual certificate is necessary for any particular establishment or any particular project. While this relieves employers of the strict duty to follow COSHH as indicated in paragraph 38, local assessment of the nature of the work may result in the need to retain full Containment Level 3 conditions or use other more stringent means of control.
40 The agents to which the exemption applies are named in the schedule to the certificate but are also marked in the guidance list on pages 12 to 23. Here, there are references that either show the specific features of containment that may be dispensed with or indicate guidance in appendices or other publications issued by the Health and Safety Commission, dealing specifically with the agent in question.
41 One example of derogation is work with Salmonella typhi , which, despite being in Hazard Group 3, does not demand use of a microbiological safety cabinet. Similarly, published guidance on blood-borne viruses and the agents of the transmissible spongiform encephalopathies shows that full Containment Level 3 may not always be necessary (see footnote reference to these publications on page 5).
Categorisation of NOTATIONS biological agents - notations used 42 The following notations are used in both the Approved List of biological agents and the guidance list: A: known to have allergenic effects; T: toxin production; D: list of workers exposed to this agent to be kept for 40 years following the last known exposure; V: an effective vaccine is available.
...... Page 10 Advisory Committee on Dangerous Pathogens ...... 43 Additional notations used in the guidance list are these:
G: gloves should be used; E: eye protection should be used; S: a microbiological safety cabinet should be used; $: a microbiological safety cabinet is not essential; f the laboratory need not be sealable for fumigation and a continuous airflow during work with the agent is not essential.
Other notations refer to footnotes, appendices in this publication or to guidance published elsewhere.
Definitions of 44 For the purposes of these definitions, ‘disease’ refers to disease caused hazard groups by infection.
Hazard Group 1: A biological agent unlikely to cause human disease.
Hazard Group 2: A biological agent that can cause human disease and may be a hazard to employees; it is unlikely to spread to the community and there is usually effective prophylaxis or effective treatment available.
Hazard Group 3: A biological agent that can cause severe human disease and presents a serious hazard to employees; it may present a risk of spreading to the community, but there is usually effective prophylaxis or treatment available.
Hazard Group 4: A biological agent that causes severe human disease and is a serious hazard to employees; it is likely to spread to the community and there is usually no effective prophylaxis or treatment available.
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GUIDANCE LIST OF BIOLOGICAL AGENTS
Bacteria
1 Refer to the exemption certificate in Appendix 23.
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Viruses
1 All strains including whitepox virus. Work with these viruses should not be carried out in the United Kingdom.
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1 Refer to the exemption certificate in Appendix 23.
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1 Refer to the exemption certificate in Appendix 23. 2 At present there is no evidence of disease in humans caused by simian T-cell lymphotropic virus (STLV). As a precaution Containment Level 3 is recommended for work with this virus, Refer to Appendix 14. 3 There is no evidence of infections caused by the agent responsible for bovine spongiform encephalopathy. Nevertheless, Containment Level 2 is recommended as a precaution for laboratory work...... Page 18 Advisory Committee on Dangerous Pathogens ......
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1 Including strains from domestic cats and exotic species, for example elephants, cheetahs. 2 Including strains originally classified as rabbitpox...... Page 20 Advisory Committee on Dangerous Pathogens ......
Parasites
1 Refer to the exemption certificate in Appendix 23...... Page 21 Advisory Committee on Dangerous Pathogens ......
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Fungi
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CONTAINMENT
Hazard, risk and 45 Hazard, in this context, expresses the potential danger associated with a containment biological agent and risk as the probability that, in certain circumstances, the hazard will be expressed as an exposure with the possibility of infection. In general, the more serious the disease the higher the hazard grouping and the more likely that infection will occur, the higher the risk. Containment practices and other forms of control are to be arranged accordingly.
46 In reality, there are many grades of risk arising from work with biological agents dependent on such factors as the scale and nature of the particular task in hand, the types of control measures used, the immune status of the individual doing the work and the susceptibility of those who may be exposed in the event of the release of the agent from the laboratory or installation. The infective dose and the route by whichinfection normally occurs are also important features that condition risk.
SELECTION OF APPROPRIATE CONTAINMENT MEASURES
47 Although COSHH states it as a requirement, it is not always appropriate to work in conditions that relate strictly to the hazard group of the agent concerned. If, for example, infection most commonly occurs via the percutaneous route, controls may be modified in some cases. Examples include work with hepatitis viruses or HIV not involving propagation or concentration. These agents are in Hazard Group 3 as are a number of potent respiratory pathogens but the most important precautions for work with blood- borne viruses such as these are to prevent or minimise the contamination of surfaces and avoid the use of ‘sharps’ whenever practicable. Therefore, current guidance shows how and where this modification may be exercised within the bounds permitted by the certificate of exemption that accompanies the Approved List of biological agents.
48 In contrast, certain agents in Group 2 that appear to have a low infectious dose and are known to be readily transmissible by the airborne route under some circumstances, are likely to require control measures additional to those generally demanded for most Group 2 agents. The containment selected must always match the risk assessment for the particular process or procedure involved in handling the agent. An example is the preparation of suspensions of Neisseria meningitidis or Corynebacterium diphtheriae. A further example of where extra care is needed, is work with drug-resistant strains such as those of Plasmodium falciparum and Mycobacterium tuberculosis. In such cases, additional procedural and/or engineering controls should be considered. It is not sufficient to rely on immunisation as the only additional protective measure.
49 Conversely, with some strains, a lower standard of containment is appropriate. Examples are naturally-occuring non-pathogenic mutants (eg E.coli K12), some genetically modified agents and attenuated vaccine strains (eg the BCG strain of M.bovis). In such cases, modified containment is
...... Page 25 Advisory Committee on Dangerous Pathogens ...... acceptable, depending on the type of operation to be performed, the quantity of material to be handled and the degree of potential exposure. A further consideration is any special susceptibility amongst the staff involved in the work (see paragraph 21). No categorisation of biological agents is rigid and therefore in certain cases, modification of the containment and procedures prescribed by COSHH is indicated. Consequently, allowance has been made for this in devising the categorisation.
50 The notations reflecting the specific modifications recommended by the ACDP are listed at paragraph 43 at the beginning of the guidance list. Less stringent containment measures must not be adopted at local level before a thorough risk assessment has been made and agreement should be reached with the local safety committee before proceeding1. Where agents in Group 3 or Group 4 are concerned, prior consultation with HSE should also take place unless specific guidance has been published.
‘MUST’ AND ‘SHOULD’
51 In illustrating the control measures to be adopted when working with biological agents, a clear distinction has to be made between ‘must’ and ‘should’. ‘Must’, or other imperative wording, indicates an essential requirement defined in legislation while ‘should’ indicates the ACDP’s strong recommendation. Where necessary, interpretative guidance on what the law requires is given along with other guidance on recommended procedures and other physical features of containment ( see the various Containment Levels and Appendices 4, 5, 6, 7, 8 and 10 as appropriate).
52 As indicated, use of the recommended additional measures and some of the other more generally applicable controls appearing elsewhere in the COSHH Regulations (see, for example, paragraph 6 Schedule 9) is subject to local assessment of risk. But, it is unlikely that employers will find reason to dispense with them if they are to maintain a safe working environment and meet the requirements of paragraph 6 (1) of Schedule 9 in the Regulations. This states that '. . . where there is a risk of exposure to a biological agent and it is otherwise not reasonably practicable to prevent that exposure then it shall be adequately controlled, (in particular by the following measures which are to be applied in the light of the results of the risk assessment’). Thus, for example, the provision of ‘appropriate and adequate washing and toilet facilities’ and the ‘prohibition of eating, drinking smoking ....’ (Schedule 9 para.6.-(1)(k)), would seem fundamental to work in any setting where there is a risk of infection. Banning mouth pipetting and specifying decontamination procedures are further examples of indisputably good practice, amongst a number cited in the Regulations for consideration during risk assessment.
1 See Safety Representatives and Safety Committee Regulations SI 1977/500 HMSO ISBN 0 11 070500 9.
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ASSESSING RISK
53 In developing the risk assessment required by COSHH (see Regulation 6 and paragraphs 8 to 13 in the Approved Code of Practice1), the person responsible for the work will need to take into account a number of key factors. These will include:
(a) the Hazard Group of the agent(s) concerned;
(b) its virulence, transmissibility, route(s) of infection;
(c) the quantity (titre, volume) of the agents in the materials to be handled;
(d) the type of work to be conducted and the likely extent of dissemination of infectious material (both in the course of the process and in the event of an accident occurring);
(e) the steps that need to be taken to prevent exposure or achieve adequate control of exposure2.
LOCAL RULES
54 Employers are obliged to provide suitable and sufficient information, instruction and training for their employees (see COSHH Regulation 12). In some cases (see paragraph 10 in Schedule 9 and paragraph 56), written information and instructions are required. In most situations, much of the requirement for information is best met by devising written local rules covering all aspects of the work. These should be designed to ensure a clear understanding by all parties of what is to be done to ensure that work is conducted safely. An important example is the disposal procedure to be used for various types of contaminated waste. Based on the requirements of COSHH, local rules should specify the containment methods and procedures for work in the laboratory or animal room or in an industrial process. When devising local rules, there should be consultation with the local safety committee and safety representatives.
55 Local rules should include information on such matters as:
(a) the nature and range of agents to which employees will be exposed;
(b) possible sources of infection;
1 An Approved Code of Practice on the control of biological agents appears with the COSHH Regulations and other Approved Codes in a single publication ISBN 0 7176 0819 0 1995. 2 See COSHH Regulations 7,8 and 9 The Control of substances Hazardous to Health Regulations 1994 SI 1994/3246 HMSO 0 11 043721 7) and Approved Code of Practice on the Control of Biological agents at paragraph 14 onwards (General COSHH ACOP (Control of Carcinogenic Substances) and Biological Agents ACOP (Control of Biologocal Agents). Control of Substances Hazardous to Health Regulations 1994. Approved Codes of Practice L5 1995 HSE Books ISBN 0 7176 0819 0)...... Page 27 Advisory Committee on Dangerous Pathogens ......
(c) an assessment of the risks to health;
(d) the procedural and physical containment measures and other precautions to be used;
(e) the selection and training of staff and supervision of their work;
(f) a policy for disinfection and disposal of infected waste;
(g) rules of conduct and, where appropriate, written guidance for ancillary and maintenance staff, contractors and visitors;
(h) maintenance and test procedures for engineering controls, for example exhaust ventilation systems, high efficiency particulate absorption (HEPA) filters, microbiological safety cabinets and other safety equipment;
(i) arrangements for health records and/or health surveillance (which may include screening procedures to determine the immune status of employees); an immunisation policy; sickness investigation; and, according to local needs, use of medical contact cards; and storage of baseline serum samples provided by staff;
(j) procedures for dealing with accidents involving exposure to biological agents (for example spillage or other accidental release of infectious materials) including methods of fumigation;
(k) the form of packaging and labelling to be used for the transportation of infectious material both on and off-site;
(I) the name of the safety officer;
(m) the name of the person to whom accidents should be reported.
SPEClFIC REQUlREMENTS FOR INFORMATION - EMPLOYERS AND EMPLOYEES
56 COSHH stipulates specifically that employers shall provide written instructions (and if appropriate display notices) which shall include:
(a) the procedure to be followed in the case of an accident or incident which may have resulted in the release of a biological agent and which could cause severe human disease’;
(b) procedures for handling Group 4 biological agents or material that may contain such agents.
1 See also A guide to the Reporting of Injuries, Diseases and Dangerous Occurrences ...... Regulations 1985 HS(R)23 1986 HSE Books ISBN 0 7176 0432 2. Page 28 Advisory Committee on Dangerous Pathogens ......
57 In addition, there is a need to provide:
(a) information on any accident or incident which may have resulted in the release of a biological agent which could cause serious human disease; and
(b) as soon as practicable thereafter, information on the causes of such an accident or incident and the measures taken to rectify the situation. Similarly, employees must report any accident or incident which has or may have resulted in the release of a biological agent which could cause severe human disease.
Selection of PROPAGATION, CONCENTRATION AND STORAGE OF BIOLOGICAL containment levels AGENTS
58 The levels of containment are intended to address the risks encountered when working knowingly with biological agents as categorised in the various Hazard Groups. Except where formal derogation applies, as specified in the certificate of exemption (see Appendix 23), COSHH requires that the Containment Level selected must match the hazard grouping of the agent as a minimum. Other exceptions may be appropriate where, for example, a particular strain of a biological agent is known to have reduced virulence (see paragraph 49) or, in the case of certain parasites, only the form non-infectious for humans is handled (see the introduction to the Approved List in Appendix 23).
WORK WITH POTENTIALLY INFECTED MATERIAL
59 In clinical laboratories and in some other types of work such as food and environmental sample-testing, there are particular difficulties as there will often be uncertainty about the presence of infectious agents in the materials under examination. All laboratories in which there is likely to be exposure to agents known to be human pathogens (whether or not they are to be propagated or concentrated) require, as a minimum, Containment Level 2. Where there is a strong indication or likelihood that specimens or samples may contain agents in Hazard Group 3 or Hazard Group 4, then the requisite additional control measures must be adopted except that in some cases, derogation may apply (see paragraphs 38 to 41).
LABORATORIES AND ANIMAL ROOMS
60 The principal control measures for laboratories and animal rooms that appear in COSHH at Part II in Schedule 9 are reproduced and highlighted by shading in the text. These have been paraphrased for ease of reading. The text of Part II of Schedule 9 in COSHH is provided in Table 1, Other requirements of COSHH are also addressed at each level of containment where the use of ‘must’ indicates a statutory duty.
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INDUSTRIAL CONTAINMENT
61 COSHH also specifies the containment measures to be applied in the use of biological agents in industrial processes. Therefore, where agents are used on a larger scale in, for example, vaccine production, the standards of control defined in Part III of Schedule 9 of COSHH apply. Part III of the schedule is reproduced in Table 2. However, it is important to note that additional controls may be needed which are not included in the table. Furthermore, COSHH allows that by applying special expertise, a selection may be made of a combination of measures from Table 2 most appropriate to the process or part of the process. (Appendix 6 provides practical guidance on the large-scale use of biological agents.) Some industrial processes are however, more like larger- scale laboratory operations and reference to the requirements for laboratory containment may be more appropriate in these cases.
DESIGN AND CONSTRUCTION OF LABORATORY ACCOMMODATION
62 The physical and procedural features of the various levels of containment should be used as a guide to the design, construction or alteration of premises where biological agents are to be handled.
DEFINITION OF TERMS
63 (a) laboratory- the room in which biological agents are handled;
(b) laboratory suite - one or more laboratories, not necessarily of the same discipline, and ancillary rooms within a section or department with shared use of facilities such as autoclaves, centrifuges etc;
(c) laboratory unit - a separate building, or self-contained suite within a buildingcontaining one or more laboratories and with ancillary rooms such as airlocks, changing rooms, showers, autoclave room.
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LABORATORY CONTAINMENT LEVEL 1
Laboratory Containment Level 1 is suitable for work with agents in Group 11. Although defined as unlikely to cause disease by infection, some agents in this group are nevertheless hazardous in other ways (ie are allergenic or may be toxigenic) and due precautions must be taken. Guidance on respiratory sensitisation is available2. Laboratory personnel must receive suitable and sufficient information, instruction and training in the procedures to be conducted in the laboratory.
1 The laboratory should be easy to clean. Bench surfaces should be impervious to water and resistant to acids, alkalis, solvents and disinfectants.
2. Effective disinfectants should be available for immediate use in the event of spillage.
3 If the laboratory is mechanically ventilated, it is preferable to maintain an inward airflow while work is in progress by extracting room air to atmosphere.
4 All procedures should be performed so as to minimise the production of aerosols.
5 The laboratory door should be closed when work is in progress.
6 Laboratory coats or gowns should be worn in the laboratory and removed when leaving the laboratory suite.
7 Personal protective equipment, including protective clothing, must be:
(a) stored in a well-defined place; (b) checked and cleaned at suitable intervals; (c) when discovered to be defective, repaired or replaced before further use.
8 Personal protective equipment which may be contaminated by biological agents must be:
(a) removed on leaving the working area; (b) kept apart from uncontaminated clothing; (c) decontaminated and cleaned or, if necessary, destroyed.
1 Some agents that would qualify for inclusion in this group may be pathogens of animals or plants (see Appendix 20). Certain additional control measures specified by Agriculture Departments may be necessary to prevent their release to the environment. 2 See Preventing asthma at work - how to control respiratory sensitisers 1994 HSE Books ISBN 0 7176 0661 9...... Page 31 Advisory Committee on Dangerous Pathogens ......
9 Eating, chewing, drinking, taking medication, smoking, storing food and applying cosmetics should be forbidden.
10 Mouth pipetting should be forbidden.
11 The laboratory should contain a basin or sink that can be used for hand washing.
12 Hands should be decontaminated immediately when contamination is suspected and before leaving the laboratory.
13 Bench tops should be cleaned after use.
14 Used glassware and other materials awaiting disinfection should be stored in a safe manner. Pipettes, for example, if placed in disinfectant, should be totally immersed.
15 Contaminated materials whether for recycling or disposal, should be stored and transported in robust and leakproof containers without spillage.
16 All waste material, if not to be incinerated, should be disposed of safely by other appropriate means.
17 Accidents and incidents should be immediately reported to and recorded by the person responsible for the work or other delegated person.
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LABORATORY CONTAINMENT LEVEL 2
Laboratory Containment level 2 must be used for work with biological agents in Hazard Group 21. Laboratory personnel must receive suitable and sufficient information, instruction and training in working safely with agents in Group 2. A high standard of supervision of the work should be maintained.
8 Personal protective equipment, including protective clothing, must be:
(a) stored in a well-defined place; (b) checked and cleaned at suitable intervals; (c) when discovered to be defective, repaired or replaced before further use.
9 Personal protective equipment which may be contaminated by biological agents must be:
(a) removed on leaving the working area; (b) kept apart from uncontaminated clothing; (c) decontaminated and cleaned or, if necessary, destroyed.
10 There should be adequate space (24 m³) in the laboratory for each worker.
11 The laboratory door should be closed when work is in progress.
1 Some agents in this group may be pathogens of animals (see Appendix 20). Certain additional control measures specified by Agriculture Departments may be necessary to prevent their release to the environment.
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12 Laboratory coats or gowns, which should be side or back fastening, should be worn and removed when leaving the laboratory suite. Separate storage (for example, pegs) apart from that provided for personal clothing should be provided in the laboratory suite.
13 Eating, chewing, drinking, smoking, taking medication, storing food and application of cosmetics in the laboratory should be forbidden.
14 Mouth pipetting should be forbidden.
15 Bench surfaces should be regularly decontaminated according to the pattern of the work.
16 When undertaking procedures that are likely to give rise to infectious aerosols, a Class I microbiological safety cabinet (BS 5726: 1992 or unit with equivalent protection factor or performance) should be used - (see Appendix 8). Safety cabinets should exhaust to the outside air or to the laboratory air extract system (see paragraph 20 at Containment Level 3 except that double HEPA filtration is not essential at Containment Level 2 and there is no need to consult with HSE before adopting the recirculation mode for air discharged from a safety cabinet). Some other types of equipment may provide adequate containment in their own right but this should be verified.
17 In most laboratories operating at Containment Level 2 where there is mechanical ventilation simply to provide a comfortable working environment, it may not be practical to maintain an effective inward flow of air. The often constant traffic in and out of Containment Level 2 rooms may interfere significantly with attempts to establish satisfactory airflow patterns. However, where a laboratory is ventilated specifically to contain airborne pathogens in the event of an accident, then engineering controls and working arrangements must be devised so as to counter the risk of airborne transmission to other areas. Maintaining an inward flow of air is necessary only when work is in progress. ‘Atmosphere’ in this context (see paragraph 3) may be taken to mean either the external air and/or other parts of the laboratory suite or building.
18 The laboratory should contain a wash basin located near the laboratory exit. Taps should be of a type that can be operated without being touched by hand.
19 Hands should be decontaminated immediately when contamination is suspected, after handling infective materials and before leaving the laboratory. When gloves are worn, these should be washed or preferably changed before handling items likely to be touched by others not wearing gloves, for example telephones, paperwork. Computer keyboards and, where practicable, equipment controls should be protected by a removable flexible cover that can be disinfected.
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20 An autoclave for the sterilisation of waste materials should be readily accessible in the same building as the laboratory, preferably in the laboratory suite.
21 Materials for autoclaving should be transported to the autoclave in robust containers without spillage.
22 There should be a means for the safe collection, storage and disposal of contaminated waste1.
23 Contaminated waste should be suitably labelled before removal for incineration1.
24 ‘Access to an incinerator’ - see paragraph 7 above, may be taken to mean an incinerator at another site but whether local or distant, carcasses for incineration must be transported in secure containers (see Appendix 11).
25 Used laboratory glassware and other materials awaiting sterilisation before recycling should be stored in a safe manner. Pipettes, if placed in disinfectant, should be totally immersed.
26 All accidents and incidents should be immediately reported to and recorded by the person responsible for the work or other delegated person.
1 See Safe disposal of clinical waste 1992 Health and Safety Commission Health Services Advisory Committee HSE Books ISBN 0 7176 0447 0.
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LABORATORY CONTAINMENT LEVEL 3
Containment Level 3 must be used for work with all biological agents in Hazard Group 31 except where specific derogation has been applied (see Appendix 23). Laboratory personnel must receive suitable and sufficient information, instruction and training in working safely with biological agents in Hazard Group 3. A high standard of supervision of the work should be maintained. A list must be kept of employees engaged in work with biological agents in Hazard Group 3 indicating the type of work done and, where known, the agent(s) to which they are exposed. This must include, as appropriate, a record of exposures (eg resulting from accidents and incidents). In general, this list must be kept for at least 10 years but paragraph 11.-(3) of Schedule 9 in COSHH shows that for exposure to some agents, an extended period of up to 40 years may be necessary.
1 Some agents in this group may be pathogens of animals (see Appendix 20). Certain additional control measures specified by Agriculture Departments may be necessary to prevent their release to the environment...... Page 36 Advisory Committee on Dangerous Pathogens ......
12 Personal protective equipment, including protective clothing, must be: (a) stored in a well-defined place; (b) checked and cleaned at suitable intervals; (c) when discovered to be defective, repaired or replaced before further use.
13 Personal protective equipment which may be contaminated by biological agents must be: (a) removed on leaving the working area; (b) kept apart from uncontaminated clothing and equipment; (c) decontaminated and cleaned or, if necessary, destroyed.
14 There should be adequate space (24 m³) in the laboratory for each worker.
15 The laboratory door should be closed when work is in progress and locked when the room is unoccupied. A biohazard sign should be posted at the entry to the laboratory.
16 Side or back fastening laboratory gowns or coats should be worn in the laboratory and removed on leaving it. These should be autoclaved before being sent for laundering. Additional protection, for example, gloves and plastic aprons, should be also be made available.
17 Eating, chewing, drinking, smoking, taking medication, storing food and applying cosmetics should be forbidden in the laboratory.
18 Mouth pipetting should be forbidden.
19 A Class I or Class III microbiological safety cabinet (BS 5726: 1992 or unit with equivalent protection factor or performance - see Appendix 8) are the most suitable for laboratory procedures likely to give rise to infectious aerosols. In some cases, equipment which is designed to contain aerosols at source may be in use but its integrity in this respect should be verified before it is accepted as an alternative to containment of the work in a safety cabinet. Where protection of the work is essential (for example cell cultures are in use) and the route of transmission of the agent concerned is primarily percutaneous, a Class II safety cabinet may be used provided that it can be shown to offer operator protection to the standard of BS 5726 under the conditions of use (see Appendix 8).
20 Safety cabinets must exhaust through a HEPA (High Efficiency Particulate Absorption) filter1 or equivalent to the outside air or into the laboratory air extract system, and in other respects such as siting, performance in use, protection factor and air filtration, should comply with the performance specifications detailed in BS 5726: 1992. If laboratories are faced with a major problem because of difficulties in
1 Only filters tested in accordance with and matching the requirements of BS: 3928 should be used...... Page 37 Advisory Committee on Dangerous Pathogens ......
arranging for the cabinet to exhaust to open air, recirculation of exhaust air through two HEPA filters in series may, in exceptional circumstances, be considered as an alternative. In this case, the maintenance of a continuous airflow into the laboratory during work with infectious material will be of particular importance (see paragraph 31) and such an option should not be adopted without prior consultation with HSE.
21 A wash basin should be provided near the exit of the laboratory. Taps should be of a type that can be operated without being touched by hand.
22 Gloves should be worn for all work with infective materials and hands should be washed before leaving the laboratory. Gloves should be washed or preferably removed before touching items that will be touched by others not similarly protected, for example telephone handsets, paperwork. Computer keyboards and, where practicable, equipment controls should be protected by a removable flexible cover that can be disinfected.
23 An autoclave for the sterilisation of items to be recycled and/or waste materials should preferably be situated within the laboratory, but if this not practicable, then one should be readily accessible in the laboratory suite.
24 Materials for autoclaving should be transported to the autoclave in robust containers without spillage.
25 There should means for the safe collection, storage and disposal of contaminated waste1.
26 Contaminated waste should be suitably labelled before removal for incineration1.
27 ‘Access to an incinerator’ - see paragraph 11, may be taken to mean an incinerator at another site but whether local or distant, carcasses for incineration must be transported in secure containers (see Appendix 11).
28 COSHH requires that the Containment Level 3 laboratory be sealable to permit disinfection. While the definition of ‘disinfection’ may be widely interpreted, in practice, it may be necessary, subject to the assessment of risk, to decontaminate by fumigating the accommodation when, for example, a spillage has occurred or when maintenance work is to be carried out.
29 Where it is not reasonably practicable for the laboratory to contain its own equipment, for example, a deep-freezer, material should be
1 See Safe disposal of clinical waste 1992 Health and Safety Commission Health Services Advisory .Committee . . . . . HSE. . . Books. . . .ISBN . . .0 .7176 . . .0447 . . .0...... Page 38 Advisory Committee on Dangerous Pathogens ......
transported and stored without spillage in properly labelled robust containers which should be opened only in Containment Level 3 accommodation.
30 All accidents and incidents should be immediately reported to and recorded by the people responsible for the work or other delegated people.
Achieving an inward 31 COSHH requires that a Containment Level 3 laboratory is maintained flow of air at an air pressure negative to atmosphere. ‘Atmosphere’ in this context may be taken to mean the external air and/or other parts of the laboratory suite or building. In effect, this means arranging engineering controls such that a continuous inward airflow into the laboratory is maintained but this is necessary generally only when work with biological agents is actually in progress. Provision should be made for comfort factors, ie supply of fresh air, temperature control.
32 One of the following means should be adopted to achieve the inward flow of air:
(a) extracting the laboratory air through independent ducting to the outside air through a HEPA filter (or equivalent);
(b) extracting the laboratory air to the outside air with a fan and HEPA filter (or equivalent) sited in a wall or window of the laboratory;
(c) ducting the exhaust air from the microbiological safety cabinet to the outside air through a HEPA filter (or equivalent); or
(d) a safe variation of these methods.
33 Whichever method is used, the requirement of COSHH Regulation 9 referring to maintenance, examination and test of control measures and specifically to ‘local exhaust ventilation’ must be observed. This means that HEPA filters and their fittings and seals must be thoroughly examined and tested at intervals not exceeding 14 months. In practice, depending on the frequency of use, these tests are commonly carried out at shorter intervals, for example, six monthly.
34 In laboratories with a mechanical air supply system, the supply and extract airflows should be interlocked to prevent positive pressurisation of the room in the event of a failure of the extract fan. The ventilation system should also incorporate a means of preventing reverse airflows. The design of systems to achieve the required inward flow of air should aim for simplicity to avoid the chances of failure due to over- complicated control mechanisms. Instrumentation should be relevant and sensitive to the factors that contribute to safety. Engineers should be asked to consider as a priority the safety features of the room when
...... Page 39 Advisory Committee on Dangerous Pathogens ......
arranging heating and ventilation and the dispersal of heat generated by equipment. In particular, the influx of cold air and the siting of ventilation outlets and extracts can have a significant effect on the performance of safety cabinets.
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LABORATORY CONTAINMENT LEVEL 4
Laboratory Containment Level 4 must be used for all work with biological agents in Hazard Group 41. A detailed code of practice should be prepared for the laboratory and a safety officer should be appointed and be directly accountable to the person identified as responsible for the work. Personnel should be over the age of 18 and must be provided with suitable and sufficient information, instruction and training on working in the laboratory. The work should be closely supervised. A list must be kept of employees engaged in work with biological agents in Hazard Group 4 indicating the type of work done and, where known, the agent(s) to which they are exposed. This must include, as appropriate, a record of exposures (for example resulting from accidents and incidents). In general, this list must be kept for at least ten years but paragraph 11.-(3) of Schedule 9 in COSHH shows that for some infections an extended period of up to 40 years may be necessary.
Those contemplating setting up a Containment Level 4 laboratory are most strongly advised to consult experienced users before commissioning any design or construction work.
1 Some agents in this group may be pathogens of animals (see Appendix 20). Certain additional control measures specified by Agriculture Departments may be necessary to prevent their release to the environment...... Page 41 Advisory Committee on Dangerous Pathogens ......
13 Personal protective equipment, including protective clothing, must be: (a) stored in a well-defined place; (b) checked and cleaned at suitable intervals; (c) when discovered to be defective, repaired or replaced before further use.
14 Personal protective equipment which may be contaminated by biological agents must be: (a) removed on leaving the working area; (b) kept apart from uncontaminated clothing and equipment; (c) decontaminated and cleaned or, if necessary, destroyed.
15 The laboratory unit should be a separate building or form an isolated part of a building.
16 There should be adequate space (24 m³) in the laboratory for each worker
17 The clean side of the airlock (see paragraph 3 above) should be separated from the restricted (‘dirty’) side by changing and showering facilities and preferably by interlocking doors. The outer door should be labelled with a ‘work in progress’ sign.
18 At all times during work in the laboratory/laboratory suite or unit there should be a second competent person present to assist in the case of emergency.
19 High performance respiratory protective equipment (two or more units - see Appendix 10) should be available in the clean side of the laboratory unit for use in an emergency.
20 There should be a telephone or other means of outside communication in the laboratory/laboratory suite.
21 A complete change of clothing should be worn in the laboratory unit. After work is finished, clothing should be removed in the dirty side of the changing area and placed in a container for autoclaving. A shower should be taken before leaving the laboratory.
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22 All effluent, including that from the shower, should be rendered safe before discharge.
23 The room in which the cabinet system is sited must be maintained at an air pressure negative to atmosphere. ‘Atmosphere’ in this context may be taken to mean the external air and/or other parts of the laboratory suite or building depending on the circumstances. In effect, this means arranging engineering controls such that a continuous inward airflow into the laboratory is to be maintained but this is necessary generally only when work with biological agents is actually in progress. Provision should be made for comfort factors, ie supply of fresh air, temperature control.
24 The usual practice is to ventilate the laboratory unit through independent ducting by a plenum and a total-loss exhaust air system. The exhaust air from the laboratory and the cabinet/cabinet system (see paragraph 27 ) must pass through two HEPA filters (or equivalent) mounted in series before it leaves the laboratory unit. Use of twin filters for incoming air is also recommended as an additional safeguard against filter or filter-seal failure.
25 A negative pressure of at least 70 Pascals (7 mm of water) should be maintained in the laboratory and a negative pressure of about 30 Pascals (3 mm of water) in the airlock. An alarm system should be fitted to detect any unacceptable change in air pressure and manometers should be displayed which can be read from both inside and outside the laboratory.
26 The supply and extract airflows should be interlocked to prevent positive pressurisation of the laboratory in the event of a failure of extract fans.
27 In practice, a sophisticated cabinet systems or ‘cabinet line’ rather than a single Class III cabinet is generally used in order to provide the necessary space for working safely and having direct access to equipment such as a refrigerator, incubator and autoclave all of which are generally built into the structure. The system, therefore, amounts to a series of interconnected Class III safety cabinets with control and indicator devices built in. The integrity of such a complex installation must be most carefully and regularly monitored to ensure that there are no leaks and that the specification and airflows through the system are at least equivalent to those specified in BS 5726:1992.
28 There should be a programme of regular validation of the continuing safe operation of control systems (for example checks on airflows, filter integrity, sensors, indicators, interlocks) coupled with routine servicing and maintenance of all safety equipment and plant. COSHH Regulation 9 in referring to maintenance, examination and test of
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control measures and specifically to ‘local exhaust ventilation’ must be observed. This means for example, that HEPA filters and their fittings and seals must be thoroughly examined and tested at intervals not exceeding 14 months. In practice, depending on the frequency of use, these tests are commonly carried out at shorter intervals, for example, six monthly.
29 An emergency electricity supply should be provided to cut in automatically in the event of a power failure.
30 An additional ventilated air-lock may be required for bringing in larger items of equipment that cannot pass through the personnel air-lock or the autoclave. Larger equipment to be removed from the laboratory should not be passed through the airlock until the laboratory and the equipment in it has been decontaminated by fumigation or other measures appropriate to the circumstances.
31 COSHH requires that the Containment Level 4 laboratory is to be sealable to permit disinfection. While the definition of ‘disinfection’ may be widely interpreted, in practice, it may be necessary to decontaminate by fumigating the accommodation when, for example, a major spillage has occurred or when maintenance work is to be carried out.
32 A double ended autoclave with interlocking doors with entry in the laboratory and exit in a clean area should be provided. It is preferable that the autoclave is built into the cabinet system.
33 Eating, chewing, drinking, taking medication, smoking, storing food and the application of cosmetics should be forbidden.
34 Mouth pipetting should be forbidden.
35 All infectious material must be stored in the laboratory unit and nowhere else.
36 All material should be made safe or safe to handle before removal from the laboratory. A double-ended dunk tank filled with an effective disinfectant, or a safe alternative system, may be required for the removal of materials that cannot be autoclaved. The methods chosen for the removal of infected materials, including all waste for incineration, should be authorised by the safety officer and specified in the local code of practice. If a dunk tank is used, it should be sealed during fumigation if the disinfectant it contains is likely to react with the fumigant to form toxic compounds.
37 All accidents and incidents (spills and other forms of exposures to infective materials) should be immediately reported to and recorded by the safety officer who should take the appropriate measures specified
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in the local codes of practice which must include the requirements for informing employees in accordance with para. 10-(3) in Schedule 9 of the COSHH Regulations.
ANIMAL CONTAINMENT
The following four levels of animal containment are suitable for work with vertebrates that are deliberately inoculated with biological agents in each of the four Hazard Groups or with material suspected of containing those agents. The containment of invertebrates is dealt with in Appendix 5.
The accommodation used for the safe containment of experimental animals should also comply with the relevant legislation and guidance concerning animal welfare - the Animals (Scientific) Procedures Act 1986.
In working with animals for any purpose there is the possibility of respiratory sensitisation1 through contact with hair and dander and dried excreta. Also, animals may have naturally-occurring persistent or latent infections which may be a hazard to those handling them. Both sensitisation and infection are hazards to be prevented or adequately controlled through observing the relevant provisions of the COSHH Regulations.
The requirements for the maintenance of animals may differ in scale because of the size and nature of the species in use and the numbers involved but the basic principles for ensuring safety which are given below are applicable for all. Local codes of practice should be prepared based on these principles. More detailed guidance on the containment of infected animals is in preparation.
Definition of terms (a) Animal room - the room in which the animals are held;
(b) animal suite - one or more animal rooms with an anteroom and other ancillary rooms separated from general corridors and service areas;
(c) animal unit - a building or separate area within a building, containing animal rooms and other facilities such as changing rooms, showers, autoclaves, store-rooms etc.
In some instances, a small suite of rooms rather than a single room may be in use for work with infected animals. The guidance below should be read accordingly.
1 See Health and Safety in animal facilities 1992 Health and Safety Commission, Education Advisory Services Committee HSE Books ISBN 0 11 886353 3...... Page 45 Advisory Committee on Dangerous Pathogens ......
ANIMAL CONTAINMENT LEVEL 1
Animal Containment Level 1 is suitable for work with vertebrates that are deliberately inoculated with biological agents in Hazard Group 1 or material suspected of containing these agents1. Personnel must receive training in working safely with animals. All those having contact with animals and waste materials arising from the work must be made familiar with the local code of practice and be aware of any other precautions and procedures that may be required, for example, to protect them against latent or persistent infections in the species in use. The person responsible for the animal experiment must ensure that all those having contact with the animals and waste materials are made aware of the particular hazards concerned.
1 Access to the animal room should be limited to authorised people.
2 The room should be easy to clean.
3 Effective disinfectants should be available for immediate use.
4 The room should be adequately ventilated.
5 All procedures should be performed so as to minimise the production of aerosols.
6 Suitable protective clothing and footwear should be worn in the animal room and cleansed, or removed, when leaving the room (see paragraphs 15 and 16).
7 Eating, chewing, drinking, smoking, taking medication, storing food for human consumption and applying cosmetics should be forbidden in the animal room.
8 Mouth pipetting should be forbidden.
9 There should be a basin or sink that can be used for handwashing.
10 Hands should be decontaminated immediately when contamination is suspected and before leaving the animal room.
11 An autoclave for the sterilisation of waste materials should be available on site.
12 Materials for autoclaving or incineration and used animal cages, should be transported without spillage.
13 Used animal cages should be decontaminated after use.
1 Some agents in this group may be pathogens of animals (see Appendix 20). Certain additional control measures specified by Agriculture Departments may be necessary to prevent their release to the environment...... Page 46 Advisory Committee on Dangerous Pathogens ......
14 All waste materials should be disposed of safely.
15 Personal protective equipment, including protective clothing, must be: (a) stored in a well-defined place; (b) checked and cleaned at suitable intervals; (c) when discovered to be defective, repaired or replaced before further use.
16 Personal protective equipment which may be contaminated by biological agents must be: (a) removed on leaving the working area; (b) kept apart from uncontaminated clothing and equipment; (c) decontaminated and cleaned or, if necessary, destroyed.
17 All accidents and incidents, including animal bites and scratches, should be reported to and recorded by the person responsible for the work or other delegated person.
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ANIMAL CONTAINMENT LEVEL 2
Animal Containment Level 2 is suitable for work with vertebrates that are deliberately inoculated with biological agents in Hazard Group 2 or viable material suspected of containing these agents1. Personnel must receive suitable and sufficient information, instruction and training in the handling of infected animals and an appropriate standard of supervision of the work should be maintained. Those having contact with the animals and waste materials arising from the work must be made familiar with the local code of practice and be aware of any other precautions or procedures that may be required, for example to protect them against latent or persistent infections in the species in use. The person responsible for the animal experiment must ensure that all those who need to know are made aware of the particular hazards concerned.
1 Access to the room must be limited to authorised people.
2 The animal room must be easy to clean. Bench surfaces must be impervious to water and resistant to acids, alkalis, solvents and disinfectants.
3 There must be specified disinfection procedures.
4 If the animal room is mechanically ventilated, it must be maintained at an air pressure negative to the atmosphere (see paragraph 13).
5 Efficient vector control measures (for example for rodents and insects) must be taken.
6 Where necessary, there must be facilities for the safe storage of biological agents
7 For procedures which involve the handling of infected material, including any infected animal, where an aerosol may be created, a safety cabinet, isolator or other suitable containment must be used.
8 An incinerator for the disposal of animal carcasses must be accessible (see paragraph 22).
9 Personal protective equipment, including protective clothing, must be: (a) stored in a well-defined place; (b) checked and cleaned at suitable intervals; (c) when discovered to be defective, repaired or replaced before further use.
10 Personal protective equipment which may be contaminated by biological agents must be: (a) removed on leaving the working area;
1 Some agents in this group may be pathogens of animals (see Appendix 20). Certain additional control measures specified by Agriculture Departments may be necessary to prevent their release to...... the environment. Page 48 Advisory Committee on Dangerous Pathogens ......
(b) kept apart from uncontaminated clothing and equipment; (c) decontaminated and cleaned or, if necessary, destroyed.
11 Suitable protective clothing and footwear should be worn in the animal room and cleansed, or removed, when leaving. A face shield or visor should be worn when inoculating animals.
12 All manipulations should be performed so as to minimise the production of aerosols.
13 The animal room should be adequately ventilated and where mechanical ventilation is used, the air from the room should be extracted to atmosphere. ‘Atmosphere’ in this context may be taken to mean the external air and/or other parts of the building. In effect, this means maintaining an inward flow of air to the room.
14 The door to the animal room should be closed when infected animals are present and should be labelled with a sign indicating the level of the work.
15 Eating, chewing, drinking, smoking, taking medication, storing food for human consumption and applying cosmetics should be forbidden in the animal room.
16 Mouth pipetting should be forbidden.
17 Facilities should be provided for hand washing, preferably in the animal room.
18 Hands should be decontaminated immediately when contamination is suspected and before leaving the animal room.
19 All waste material, including animal bedding, should be rendered non- infective before disposal.
20 An autoclave for the sterilisation of contaminated waste materials should be accessible on site.
21 Material for autoclaving or incineration and used animal cages, should be transported without spillage.
22 ‘Access to an incinerator for the disposal of animal carcasses’ (see paragraph 8 above), may be taken to mean an incinerator at another site but whether local or distant, carcasses and any other material for incineration must be transported in secure containers (see Appendix 11).
23 Used animal cages should be rendered non-infective by disinfection, fumigation or heat treatment (steaming or autoclaving).
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24 Work surfaces should be disinfected after use.
25 If floor drains are installed, the traps should always contain water. Drain traps should regularly be disinfected and cleaned.
26 All accidents and incidents, including animal bites and scratches, should be reported to and recorded by the person responsible for the work or other delegated person.
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ANIMAL CONTAINMENT LEVEL 3
Animal Containment Level 3 is suitable for work with vertebrates that are deliberately inoculated with biological agents in Hazard Group 3 or viable material suspected of containing these agents1. Personnel must receive suitable and sufficient information, instruction and training, in working safely with the animals to be used. A high standard of supervision of the work should be maintained. Those having contact with the animals and waste materials arising from the work must be made familiar with the local code of practice and be aware of any other precautions or procedures that may be required, for example to protect them against latent or persistent infections in the species in use. The person responsible for the animal experiment must ensure that all those who need to know are made aware of the particular hazards concerned.
Although subject to an assessment that indicates a significant risk to the health of staff (see COSHH Schedule 9 paragraph 2 and paragraph 11), a list should be kept of the names of those employees who may be exposed to biological agents in Hazard Group 3 through contact with infected animals or waste materials. The record must indicate the type of work done and, where known, the agent(s) to which employees are exposed. This must include, as appropriate, a record of exposures (eg resulting from accidents and incidents). If kept, the list must be retained for at least ten years but paragraph 11 of Schedule 9 in COSHH shows that for some agents, an extended period of up to 40 years may be necessary.
1 Some agents in this group may be pathogens of animals (see Appendix 20). Certain additional control measures specified by Agriculture Departments may be necessary to prevent their release to the environment.
......
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13 Personal protective equipment, including protective clothing, must be: (a) stored in a well-defined place; (b) checked and cleaned at suitable intervals; (c) when discovered to be defective, repaired or replaced before further use.
14 Personal protective equipment which may be contaminated by biological agents must be: (a) removed on leaving the working area; (b) kept apart from uncontaminated clothing and equipment; (c) decontaminated and cleaned or, if necessary, destroyed.
15 The animal room should be separated from any general thoroughfare by an anteroom with two doors or be sited within an animal suite or animal unit.
16 The anteroom should have facilities for the storage of protective clothing.
17 Showering facilities should be provided in the anteroom or within the animal suite or unit.
18 A specific biohazard sign indicating the level of the work should be posted at the entry to the room and the room or suite should be locked when staff are absent.
19 COSHH requires that animal accommodation at Containment Level 3 is maintained at an air pressure negative to atmosphere and that extracted air is HEPA-filtered or equivalent. ‘Atmosphere’ in this context may be taken to mean the external air and/or other parts of the animal suite or unit. In effect, this means arranging engineering
......
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controls such that a continuous inward airflow into the room is to be maintained. Provision should be made for comfort factors for both animals and staff, ie supply of fresh air, temperature control. Air should be extracted through ducting through a HEPA filter or by extracting air with a fan and HEPA filter sited in a wall or window. The ventilation system should incorporate a means of preventing reverse airflows. The supply and extract systems should be interlocked to prevent positive pressurisation of the room in the event of failure of the extract fans, Further guidance on alternative means by which the inward flow of air may be achieved is given under Laboratory Containment Level 3 where there is also reference to the periodicity of testing ventilation equipment required by COSHH.
20 The animal room at Containment Level 3 is to be sealable to permit disinfection. While the definition of ‘disinfection’ may be widely interpreted, in practice, it may be necessary to decontaminate by fumigating the accommodation when, for example, a spillage has occurred, at the end of the experiment or when maintenance work is to be carried out.
21 Where floor drains are installed, the drain traps should be kept filled. They should be disinfected and cleaned regularly and at the end of each experiment.
22 Animals infected with Hazard Group 3 agents should be housed in safety cabinets or isolators or in other forms of primary containment that are provided with HEPA-filtered exhaust ventilation or equivalent.
23 Where it is not reasonably practicable to use primary containment for animals, personnel should wear a complete change of clothing and use high performance protective respiratory equipment at all times.
24 When undertaking procedures with infected materials that are likely to give rise to aerosols (inoculation procedures, necropsy and harvesting infected tissues and fluids), a Class I or Class III microbiological safety cabinet (BS 5726: 1992 or a unit offering an equivalent level of protection), an isolator or other suitable means of containment is to be used. The containment unit used must exhaust to the outside air or to the room air extract system via a HEPA filter (or equivalent).
25 Protective clothing, including footwear and gloves, supplemented where necessary by heavy duty or waterproof clothing, should be worn in the animal room and removed when leaving the room. The clothing should be disinfected or autoclaved after use.
26 Eating, chewing, drinking, smoking, taking medication, storing food for human consumption and applying cosmetics should be forbidden in the animal room.
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27 Mouth pipetting should be forbidden.
28 Gloves should be worn for all work with infective materials and hands should be washed before leaving the animal room. Gloves should be washed or preferably removed before touching items that will be touched by others not similarly protected, for example telephone handsets, paperwork. Computer keyboards and, where practicable, equipment controls should be protected by a removable flexible cover that can be disinfected.
29 There should be a wash-basin fitted with taps that can be operated without being touched by hand.
30 Hands should be decontaminated immediately when contamination is suspected and after removal of protective clothing when leaving the anteroom or suite.
31 There should be means for the safe collection, storage and disposal of contaminated waste.
32 An autoclave for the sterilisation of waste materials should be available on site. The autoclave should be sited in the same building as the animal room or animal suite.
33 Material for autoclaving or incineration and used animal cages, should be transported without spillage.
34 All waste material, including animal bedding, should be rendered non- infective before disposal.
35 ‘Access to an incinerator’ (see paragraph 12 above), may be taken to mean an incinerator at another site but whether local or distant, carcasses or other material for incineration must be transported in secure containers (see Appendix 11).
36 Used animal cages should be rendered non-infective by disinfection, fumigation, heat treatment (steaming or autoclaving).
37 Work surfaces should be disinfected after use and the room disinfected or fumigated at the end of each experiment.
38 Infective materials taken into the animal room, or removed from it, should be transported in sealed containers.
39 All accidents and incidents, including animal bites and scratches, should be reported to and recorded by the person responsible for the work who should take the appropriate measures specified in the local code of practice.
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ANIMAL CONTAINMENT LEVEL 4
Animal Containment Level 4 is suitable for work with vertebrates that are deliberately inoculated with biological agents in Hazard Group 4 or material suspected of containing these agents 1. Written instructions must be prepared for work at this level, and a safety officer should be appointed and be accountable to the person identified as being responsible for the work. Personnel should be over the age of 18 and must have had specific training in the handling of the animals infected with Hazard Group 4 biological agents and in the use of the safety equipment and controls of the animal room. The work should be closely supervised. The person responsible for the animal experiment must ensure that all those having contact with the animals and waste materials are made aware of the nature of the agent in question and of any specific precautions and procedures that may be required.
Although subject to an assessment that indicates a significant risk to the health of staff (see COSHH Schedule 9 paragraph 2 and paragraph 11), a list should be kept of the names of those employees who may be exposed to biological agents in Hazard Group 4 through contact with infected animals or waste materials. The record must indicate the type of work done and, where known, the agent(s) to which employees are exposed. This must include, as appropriate, a record of exposures (for example resulting from accidents and incidents). If kept, the list must be retained for at least ten years but paragraph 11 of Schedule 9 in COSHH shows that for some agents, an extended period of up to 40 years may be necessary.
1Some agents in this group may be pathogens of animals. Certain additional control measures specified by Agriculture Departments may be necessary to prevent their release to the environment......
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13 Personal protective equipment, including protective clothing, must be: (a) stored in a well-defined place; (b) checked and cleaned at suitable intervals; (c) when discovered to be defective, repaired or replaced before further use.
14 Personal protective equipment which may be contaminated by biological agents must be: (a) removed on leaving the working area; (b) kept apart from uncontaminated clothing and equipment; (c) decontaminated and cleaned or, if necessary, destroyed.
15 The clean side of the airlock should be separated from the restricted side by changing and showering facilities and preferably by interlock- ing doors. The outer door should labelled with a work in progress sign.
16 The room must be maintained at an air pressure negative to atmosphere. ‘Atmosphere’ in this context may be taken to mean the external air and/or other parts of the suite or building depending on the circumstances. In effect, this means arranging engineering controls such that a continuous inward airflow into the accommodation is to be maintained. Provision should be made for comfort factors, ie supply of fresh air, temperature control.
17 A negative pressure of at least 70 Pascals (7 mm of water) should be maintained in the animal room and a negative pressure of about 30 Pascals (3 mm of water) in the airlock. An alarm system should be fitted to detect any unacceptable change in air pressure and manometers should be displayed which can be read from both inside and outside the laboratory.
18 In general, the principle of primary containment of hazards implicit in COSHH should always be applied to controlling the risks from infected
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animals. Therefore, animals held at Containment Level 4 should be accommodated and manipulated within a Class III microbiological safety cabinet (BS 5726:1992 or unit offering an equivalent level of protection) or a cabinet line or some form of enclosed isolator suitable for the nature of the species (size and disposition) and the operations to be performed are such that this form of close containment may not be practical. It may be appropriate, for example, for small mammals such as mice but not for larger animals. Where this is the case, and the risks involved have been adequately assessed, ‘other suitable containment’ (see paragraph 5) may be taken to include use of alternative engineering controls such as exhaust-ventilated caging or, as a last resort, the use of respiratory-protective equipment of proven efficacy.
19 All exhaust air must be filtered through two HEPA filters mounted in series before it is ducted to the outside air or to the room air extract system.
20 The supply and extract airflow should be interlocked to prevent positive pressurisation of the room in the event of a failure of the extract fan and an emergency electricity supply should be provided to cut in automatically in the event of a power failure. The ventilation system should incorporate a means of preventing reverse airflows.
21 A double ended autoclave with interlocking doors with entry in the laboratory and exit in a clean area should be provided.
22 An additional ventilated airlock that can be fumigated may be required for passage of equipment that cannot enter the laboratory through the personnel airlock or double-ended autoclave).
23 The animal room at Containment Level 4 is to be sealable to permit disinfection. While the definition of ‘disinfection’ may be widely interpreted, in practice, it may be necessary to decontaminate by fumigating the accommodation when, for example, a spillage has occurred, at the end of the experiment or when maintenance work is to be carried out.
24 A complete change of clothing should be worn. The clothing should be in removed in the dirty side of the changing area after work and placed in a container for autoclaving. A shower should be taken before leaving the laboratory unit.
25 All effluent, including that from the shower, should be rendered safe before discharge.
26 There should be a programme of regular validation of the continuing safe operation of control systems (for example checks on airflows, filter integrity, sensors and indicators) coupled with routine servicing and
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maintenance of all safety equipment and plant. COSHH Regulation 9 in referring to maintenance, examination and test of control measures and specifically to ‘local exhaust ventilation’ must be observed. This means for example, that HEPA filters and their fittings and seals must be thoroughly examined and tested at intervals not exceeding 14 months. In practice, depending on the frequency of use, these tests are commonly carried out at shorter intervals, for example, six monthly.
27 All waste material should be rendered non-infective before being removed from the animal room and should be autoclaved. Animal bedding materials and carcasses should be incinerated immediately on removal. A double ended dunk tank filled with an effective disinfectant may be required for the removal of materials that cannot be autoclaved. Removal of materials in this manner should be under- taken only with the authorisation of the safety officer and under conditions defined in the local code of practice. If a dunk tank is used, it should be sealed during fumigation if the disinfectant it contains is likely to react with the fumigant to form toxic compounds.
28 At all times during work in the laboratory unit there should be a second competent person available to assist in the case of emergency.
29 High performance respiratory protective equipment (two or more units - see Appendix 10) should be available in the clean side of the laboratory unit for use in an emergency.
30 There should be a telephone or other means of outside communication inside the laboratory unit.
31 Eating, chewing, drinking, smoking, taking medication, storing food for human consumption and applying cosmetics should be forbidden in the animal room.
32 Mouth pipetting should be forbidden.
33 Infective material should be stored in the animal room, but where this is impractical such material taken into the room (or removed from it to another Containment Level 4 room on site) should be transported under the supervision of the safety officer, in sealed containers which have been externally disinfected.
34 Where floor drains are installed, the drain traps should be kept filled and sealed until required. The effluent from traps should be rendered non-infective before discharge to a sewerage system. The drain traps should be disinfected and cleaned regularly and at the end of each experiment.
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35 All accidents and incidents, spills and accidental exposures to infective materials should be immediately reported to and recorded by the safety officer who should take the appropriate measures specified in the local codes of practice.
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Table 1 Containment measures for health and veterinary care facilities, laboratories and animal rooms1
1 This table reproduces Part II of Schedule 9 in the COSHH Regulations 1994...... Page 60 Advisory Committee on Dangerous Pathogens ......
Table 2 Containment measures for industrial processes1
1 This table reproduces Part III of Schedule 9 in the COSHH Regulations 1994...... Page 61 Advisory Committee on Dangerous Pathogens ......
APPENDIX 1 INFORMATION, INSTRUCTION AND TRAINING
1 Adequate information, instruction and training on all relevant aspects of health and safety at work are most important in achieving high standards; their value cannot be overemphasised.
2 Moreover, the need for a sound understanding of the principles and practice of infection control is not confined to microbiology laboratories ie where biological agents are intentionally propagated or stored. It is just as relevant in many other types of laboratory as material of human, animal or environmental origin may carry a significant risk of infection. The general principles of occupational hygiene and infection control should be included in the syllabus of all professional bodies and teaching establishments concerned with the education and training of medical, veterinary, scientific and technical students.
3 Employers have responsibilities under the Health and Safety at Work etc Act (HSWA) and the Management of Health and Safety at Work Regulations (MHSWR) to provide information, instruction and training for their employees. The COSHH Regulations are specific to exposure to biological agents and except where the HSWA and MHSWR go beyond the requirements of COSHH, COSHH would prevail (see Regulation 12 and paragraph 10 in Schedule 9). Employees also have a duty in law to provide their employers with information when they have knowledge of any accident and incident that has or may have resulted in the release of a biological agent which could cause severe human disease and thereby pose a threat to health.
4 Information and training provided by the employer should include instruction in the nature of the potential hazards and in the practical use of the procedures, techniques and safety equipment that are required to minimise the risk of infection. But the need for this is not limited to those who work directly with biological agents (ie at the bench); it is also necessary for auxiliary staff (for example clerks, cleaners, porters) who must also receive comprehensible instruction appropriate to their needs. This will be particularly important where the laboratory manager(s) is not primarily responsible for the recruitment and supervision of such staff, for example, when work is contracted out. In such cases, the two or several employers need to co- operate in supplying what is required to protect those workers.
5 To be of any value information, in whatever form, must be capable of being readily understood by those to whom it is addressed. It should take account of their level of training, knowledge and experience. Special consideration should be given to any employees with language difficulties or with disabilities that may impede their receipt of information. For employees with little or no understanding of English, or who can not read English, employers may need to make special arrangements. These could include providing translations, using interpreters, or in some cases replacing written notices with clearly understandable symbols or diagrams. Thus, except in
...... Page 62 Advisory Committee on Dangerous Pathogens ...... certain cases, information can be provided in whatever form is most suitable in the circumstances, so long as it is fully comprehensible.
6 The employer, or the employing body, should appoint a person for the management of health and safety training. This could, for example, form part of the duties of the safety officer who should regularly review the standards required in consultation with the safety committee (see Safety Representatives and Safety Committee Regulations 1985). No new member of staff should be permitted to work with biological agents or handle infectious materials (for example in disposal procedures) until he/she has received suitable instruction. One particularly important feature of instruction that is often neglected is the safe operation of microbiological safety cabinets (see Appendix 8).
7 In some cases, formal courses may be necessary, followed by refresher courses and lectures or other forms of instruction to keep personnel up to date with any changes that may have an impact on health and safety, for example, the introduction of new equipment, materials and methods. A variety of audio-visual aids is available and some colleges and health authorities offer comprehensive courses on microbiological safety.
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APPENDIX 2 SUPPLEMENTARY CONTAINMENT MEASURES FOR AGENTS IN GROUP 2
1 It is clear that a dilemma can occur in those laboratories that regularly handle agents which are appropriately assigned to Hazard Group 2 on clinical criteria and on the basis of the strict definition for that Group but which can present a significant risk of serious infection in some laboratory operations.
2 COSHH requires that agents in Group 2 are handled in the laboratory at Containment Level 2 as a minimum. In general, work with agents in Group 2 may be conducted on the open bench although care must always be taken to minimise the production of aerosols. For manipulations such as vigorous shaking or mixing and ultrasonic disruption etc, a microbiological safety cabinet or equipment which is designed to contain the aerosol must be used. All manipulations involving infectious agents should be addressed in the risk assessment and specific local rules developed to ensure that the work is conducted safely. In some cases, the nature of the work may even dictate the need for full Containment Level 3 conditions.
3 Although most agents in Group 2 fit the epidemiological and clinical criteria reflected in the definition, certain members of this group should always be handled in a safety cabinet or be otherwise suitably contained. In some cases, gloves and eye protection should be used routinely. It is suggested therefore that a notional ‘2+’ level of containment be adopted for such agents. Examples of the pathogens that should be included in this group are those known to have been the cause of serious or even fatal infections when involved in such simple operations as making suspensions for serotyping or simply opening centrifuge containers. Some Hazard Group 2 agents are known to infect via apparently intact mucosae or through skin contact and can present an enhanced risk.
4 Depending on the nature of the intended work, examples of agents that should be afforded ‘2+’ containment are:
Borrelia burgdorferi Leptospira interrogans var. Borrelia duttoni icterohaemorrhagiae, canicola, Borrelia recurrentis hebdomadis Chlamydia trachomatis Sporothrix schenkii Clostridium botulinum Streptobacillus moniliformis Corynebacterium diphtheriae Treponema pallidum and other Cryptococcus neoformans treponemes Legionella pneumophila Vibrio cholerae (including El Tor) Neisseria meningitidis
5 Viruses, fungi and parasites should also be considered in this context.
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APPENDIX 3 WORKING WITH PARASITES
1 The principle of matching the level of containment with the hazard grouping of an agent applies to all infectious biological agents. However, the introduction to the Approved List of biological agents makes clear that some features of containment may be dispensed with when working with the non- infectious stages in the life-cycle of parasites.
2 Furthermore, in some cases, even this condition need not apply. The Schedule to the certificate of exemption accompanying the Approved List specifies a number of parasites in Hazard Group 3 (Plasmodium falciparum, Taenia solium, Leishmania and Echinococcus spp), for which full Containment Level 3 need not be used.
3 Work with the species of parasite listed in the Schedule does not generally require an inward flow of air to the laboratory or use of a microbiological safety cabinet as none of these agents is normally infectious by the airborne route. For working with these agents in quantity in research, for example a separate room should be used or a designated area in a larger laboratory. There must be strict attention to avoiding sharps injuries and surface contamination (including equipment controls, telephones and computer keyboards etc). Sharps should be excluded altogether as far as is practicable. Unhealed wounds and lesions on exposed skin should be covered with waterproof dressings and hands should be washed regularly and immediately when contamination is noted. If gloves are worn, these too should be washed or discarded before they contaminate items likely to be handled by others. Where drug-resistant strains of parasites are being handled, particular care is needed and work should be confined to a separate room. Insect vectors must be securely contained (see Appendix 5). Local assessment will indicate what additional precautions are necessary.
Diagnostic work 4 Where, for example, there is a need to make a simple diagnosis of malaria or leishmaniasis from a blood film or stools or tissues are examined for evidence of infection with Taenia solium or Echinococcus spp, the work may be conducted at Containment Level 2 provided that precautions are taken against sharps injury, other forms of auto-inoculation and ingestion. A safety cabinet and inward flow of air is not required for this type of work. Strict attention must however, be paid to the hygiene measures listed above.
In all cases, there must be safe means of disposal of infected waste.
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APPENDIX 4 WORK WITH RABIES VIRUS
The risk to laboratory 1 Rabies is a highly pathogenic virus for which there is no treatment once the workers symptoms of disease have begun. Infection is usually transmitted through the skin or less commonly the mucous membranes. Prophylactic vaccination is effective and in recent years has become very reliable, simple and harmless. It is therefore essential that any person intending to work with rabies is vaccinated and that an appropriate level of immunity is maintained.
2 For diagnostic and laboratory work, Containment Level 3 is considered appropriate for the human risk. However, for work requiring propagation of the virus, secure secondary containment as required by the United Kingdom Departments of Agriculture1 is essential because of the potential risk of transmission of the virus to the animal population.
The risk to animals 3 Britain is rabies free, there having been only two cases of the disease in animals outside quarantine since 1922. These were both imported dogs and occurred in 1969 and 1970. Departments of Agriculture have the responsibility of ensuring that rabies does not gain entry to the animal population. If the disease did enter the country and became established in domestic and wild animal populations, the effects could be disastrous and would inevitably alter our whole approach to human contact with pets and other animals.
The Specified Animal 4 In relation to laboratory work with rabies, the prime concern is to ensure Pathogens Order 1993 that there can never be any accidental escape of the virus from any laboratory into the native animal population. Anyone who wishes to import or to work with rabies virus must apply to the appropriate Agriculture Department for a licence which, in England, Scotland and Wales is issued under the Specified Animal Pathogens Order 1993. The containment facility must be inspected and approved by an officer of the Agriculture Department before a licence may be issued and continuance of the licence will be subject to satisfactory periodic inspection reports thereafter.
1 MAFF, Hook Rise South, Tolworth, Surbiton, Surrey KT6 7NF WOAD, Government Buildings, St Agnes Road, Gabelpa, Cardiff CF4 4YH SOAFD, Peatland House, 47 Robbs Loan, Edinburgh EH14 1TW DANI, Dundonald House, Upper Newfoundlands Road, Belfast BT4 3SB ...... Page 66 Advisory Committee on Dangerous Pathogens ......
APPENDIX 5 THE CONTAINMENT OF INVERTEBRATES
1 Many invertebrates are the natural or experimental hosts or vectors for a range of infectious agents. Work with invertebrates may vary from simple species identification to detection of any infectious agents they may be carrying through to their deliberate infection for research purposes.
2 The important invertebrates are:
Protozoa; Platyhelminthes; Aschelminthes; Mollusca; Annelida; Arthropoda; Echinodermata.
3 Where invertebrates are known to be infected or may be infected with biological agents, the principles of containment described for animal rooms must be applied. If, for example, a wild-caught invertebrate is to be examined for the presence of a pathogen of humans that it may normally be expected to transmit (for example Trypanosoma cruzi in a triatomine bug), then work should be done at the level of containment appropriate to the hazard grouping of the agent concerned1. An assessment of risk is necessary, based on the intended nature of the work. In adopting the principles used in the containment of animals, the following additional points should be borne in mind.
(a) Separate rooms should be used for infected and non-infected invertebrates.
(b) Invertebrates should be contained appropriately according to whether they:
(i) live in water (aquatic);
(ii) are amphibious;
(iii) crawl or jump;
(iv) fly.
(c) Aquatic or amphibious invertebrates should be kept in tanks with lids to prevent escape.
1 Note that full Containment Level 3 is not always required for all work with a Hazard Group 3 agent. Non-infective stages in the life-cycle of a paasite and certain agents for which a derogation has been allowed (see Exemption Certficate with the Approved List of biological agents) may not always demand an inward airflow or use of a safety cabinet for example...... Page 67 Advisory Committee on Dangerous Pathogens ......
(d) For invertebrates that crawl, jump or fly, the following additional precautions should be taken:
(i) rooms should be insect-proof;
(ii) ventilation inlets and outlets should be screened;
(iii) entry to the rooms should be through an airlock; consideration should be given to placing ‘insectocutors’ in the airlock;
(iv) measures should be taken to enable escaped invertebrates to be easily detected and recaptured or destroyed;
(v) a laboratory sink should be provided with an adequate trap for waste; if there is a possibility that escaped invertebrates could escape through the trap, liquid waste should be treated before disposal (preferably by heat);
(vi) solid waste is most effectively treated by heat because it may harbour invertebrates that may not be killed by chemical disinfectants or fumigants;
(vii) insecticidal sprays may be necessary in an emergency but it should be remembered that their use in a small room may render the room unfit for accommodating invertebrates for a long period if not permanently; non- residual type insecticides should be chosen:
(xiii)arthropods may be chilled to reduce their activity and minimise the risk of escape;
(ix) at Containment Levels 1 and 2, flying or crawling arthropods should be handled on white trays to detect escapees;
(x) for ticks and mites, containers should be kept over trays of oil;
(xi) flying insects infected with agents in Hazard Groups 2, 3 or 4 should be kept in double cages (for example, a sleeved netting cage inside a clear substantial plastic bag); both enclosures should be labelled;
(xii) experimental cages/containers should be numbered and labelled or otherwise documented to indicate the hazard;
(xiii)at Containment Levels 3 and 4, flying or crawling arthropods should be kept in identified lots and each lot accounted for; they should also be handled in safety cabinets, isolators or partial
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containment devices that are provided with HEPA-filtered exhaust ventilation or equivalent;
(xiv) laboratories receiving potentially infected invertebrates for identification or examination,where the specimens are not known to be dead, should open the container in a safety cabinet or other safe form of enclosure; a record should be made of the number of individual invertebrates at the earliest practicable time; each invertebrate should be accounted for as the work proceeds through to final fixation or disposal;
(xv) where identification of flying or crawling invertebrates alone is required, the container may be frozen at -20°C for two hours to kill them.
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APPENDIX 6 THE LARGE-SCALE USE OF BIOLOGICAL AGENTS
Introduction 1 The definition of biological agents in the COSHH Regulations does not differentiate between traditional and recombinant organisms (genetically- modified organisms - GMO) insofar as the Regulations are concerned with the risks to workers which might arise due to any infection or allergenic, toxic or other harmful effect whatever the nature of the agent concerned. All these possible effects must be taken into account when designing safe plant, buildings and systems of work suitable for the large-scale use of such agents. However, given that the definitions of biological agents in Groups 2, 3 and 4 relate to their ability to infect, this Appendix primarily provides guidance on countering the risk of infection when operating at large scale. Essentially, it expands on the criteria for industrial containment in Part III of Schedule 9 in the COSHH Regulations 1994.
2 Those same criteria also appear in legislation on the contained use of GMO for which there may be further requirements to safeguard the environment. Under the Health and Safety at Work Act 1974 the Health and Safety Commission has implemented the Genetically Modified Organisms (Contained use) Regulations 1992 which contain the regulatory requirements for both small and large scale use of GMO. To support these Regulations, HSE, on the advice of the Advisory Committee on Genetic Modification (ACGM), has issued guidance that describes arrangements for work with GMO at large scale. Despite these two separate treatments, there are great similarities.
3 Wild-type biological agents have been in use in some cases for thousands of years in many sectors of industry. These range from the highly traditional to those which have only been in existence during the last decade. In the food and drink industry which forms the largest application of industrial biotechnology in the western world, micro-organisms are used for the manufacture of cider, wine, beer, spirits, yeast and bread, cheese, yoghurt and a range of fermented milk products. The processes in these industries are largely modern industrial adaptations of the historically developed methods. They show wide variations in technique and equipment. The range of industrial practice, which has become an accepted feature of these industries, has built up in a number of ways but during the 20th century many new applications of biotechnology have been developed. Waste treatment has ceased to be just a physical separation process and in the industrial enzyme and pharmaceutical areas a wide range of new techniques and equipment is used, ranging from tissue culture and cell culture in roller bottles to large sterile stainless steel fermenters for the manufacture of antibiotics. Because of the great diversity of the industries that use biotechnology and their accepted modes of ‘good practice’, no simple guidance can be given to cover in detail the accepted processing standards of each industry sector. Such practices are currently being gathered together in the form of Good Manufacturing Practice (GMP) for each sector and for European Standards.
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4 Part I of Schedule 9 of COSHH, at paragraph 2(1)(b), states that the Schedule shall have effect with a view to protecting the health of employees, but that it shall not apply where the results of the assessment made under Regulation 6 indicate that there is no significant risk to health associated with the agent in question. It is, therefore, part of the duty of the employer in carrying out the assessment to examine all aspects of risk which may arise, such as toxicity and allergenicity in addition to the risk of infection which is summarised in para 3(4) and which demands the minimum containment levels required by paragraph 8(3)(e) and paragraph 8(4)(a)(b)(c).
5 Measured by any normal industrial criteria, by far the most important biotechnology product sector is food and drink, which traditionally always has and does use organisms which are now classified in Hazard Group 1, (unlikely to cause human disease by infection). Because of this, no containment measures are specified in Part III of Schedule 9 to the Regulations for work of this type. In fact, over 99% of all industrial biotechnology use falls within this area including all the food and drink applications and many of the enzyme and antibiotics production processes. Only a small range of industrial processes, mainly in the pharmaceutical and waste disposal areas use organisms in Groups 2, 3 and 4, and to which the requirements of Schedule 9, Part III apply.
6 The purpose of this Appendix is not to elaborate the wide range of practices that use Group 1 agents although some of these are potent respiratory sensitisers requiring due precautions to be taken to conform with COSHH. The intention is to provide guidance on the ways of achieving a safe standard of operation in those areas of manufacture where use is made of agents in Hazard Groups 2, 3 and 4, all of which are pathogens of humans.
7 Where appropriate for reasons of product quality and GMP, some of the practices used in the higher containment categories should also form part of the accepted norm of manufacture involving Group 1 agents. An example of this might be the pharmaceutical industry with its overriding need for maintaining product sterility. This industry will often use fermentation practices which are in every way as stringent as those required for Group 2 agents but for GMP rather than health and safety reasons. These specific needs have been developed over a long period to provide the correct environment in which reliable and successful manufacture can be achieved. There should be no confusion between the use of a containment measure, for example fermenter exhaust filtration or the use of a condensate sealed double mechanical seal developed as a process GMP requirement and the health and safety requirements for the satisfactory handling of agents in Groups 2, 3 and 4.
8 The aim here is to provide an amplification of the containment measures in Part III of Schedule 9 in the COSHH Regulations bearing in mind that the schedule at paragraph 8(2)(b) indicates that ‘he (ie the employer) may combine measures in Part III from different categories of containment on the
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basis of a risk assessment related to any particular process or part of a process...‘. This Appendix covers management systems, fermentation systems - primary containment, process rooms and buildings, secondary containment and personal protection measures.
9 The guidance will be based primarily on Group 2 agents where, traditionally, words such as ‘minimise’ and ‘optional’ have been used. This is therefore the area of greatest uncertainty in which the guidance will attempt to provide maximum practical advice. Any different requirements for work with agents in Groups 3 and 4 will be introduced as necessary.
Management systems 10 Before beginning work on large scale use, all operatives must receive adequate documented training in all operations in which they will be involved including routine work and in dealing with emergencies. All operations should be carried out, wherever possible, according to standard operating procedures. Written instructions must be provided (and, if appropriate, notices must be displayed) for the information of employees in case of any accident or incident which results or might result in the release of a biological agent which could cause severe human disease. For work with agents in Groups 3 and 4, emergency plans should be part of an operations manual for the site and the contained area. All operatives must be trained in emergency response. The organisation must have a properly documented spillage policy for use in emergencies. This should show precisely what steps have to be taken and who is responsible for implementing them.
11 Where appropriate, an environmental monitoring programme should be implemented to validate the efficacy of the containment conditions within the work area and also the immediate surrounding areas, especially if the contained fermenter suite is located as part of an existing building.
Large scale/ 12 Historically, industry has been in some doubt as to the meaning of large small scale and small scale and the significance, if any, of any arbitrary limit such as 10 litres. In present-day industry it is not uncommon for research laboratories to carry out work using bench-mounted equipment of 200 litres volume or sometimes more. Conversely, for highly active, fragile or small quantity production, industry will utilise fermenters or other fermentation reaction vessels of less than 10 litres. The important parameter in all of these instances is not the scale of operation but the intention. If the intention of the persons carrying out the work is to restrict such activities to the purposes of teaching, research, development, ie non-commercial, then such work can, for genetically modified organisms, be regarded as a ‘Type A operation’ 1 and, for organisms in general, as ‘small scale’. The volume should be such that, to be regarded as small scale, as well as being carried out under conditions of good microbiological practice, it is possible to render the organisms inactive by standard laboratory decontamination techniques. All other work which is carried out to supply for sale or to offer for sale must be regarded as large scale or industrial use, irrespective of volume.
1 see A guide to the Genetically Modified (Contained Use) Regulations 1992 Health and Safety Executive ISBN 0 11 882049 4...... Page 72 Advisory Committee on Dangerous Pathogens ......
Fermentation systems 13 In planning a new or modifying an existing industrial installation, great care should be taken to ensure that the general layout is suitable for the operation. There should be sufficient space around all vessels and component equipment for normal operation, The space should also be adequate to ensure that emergency work and spillages can be dealt with without endangering the safety of the operatives involved.
14 The fermenter or its equivalent process vessel or container, depending upon the industry, must be regarded as the primary containment and, where appropriate, would normally be subjected before each run to validated leak test procedures with all connections including the agitator seal in place, and before the introduction of viable organisms. The design of valves should be such that emphasis is on functional integrity, ie leak-proofness rather than cleanability. Similar considerations apply to pipework. For Group 2 applications satisfactory leak-proof connections can be achieved using single O-ring flanged joints or using quick release, dairy type, couplings. For both Group 3 and 4 applications, pipework should be all welded wherever practicable. The leak-proofness of all pipework connections and welded pipework should be validated each run.
15 Some fermentations require agitation of the reactor contents to achieve adequate air dispersion. This is normally achieved by means of impellers on an agitator shaft, either top or bottom driven. Alternatives are the use of magnetic couplings or air lift techniques. Where agitators are fitted their seals may be single or double face mechanical seals for Group 2 work. For Group 3 and Group 4, it is essential to use a double face mechanical seal with condensate fed to the interspace. The condensate temperature should be continuously monitored and alarmed.
16 Most fermentations carried out in aerobic conditions require sterile air, which is usually generated using an ‘oil free’ compressor. Sterility is often achieved by use of filtration through a 0.22 µm cartridge filter. Some users also achieve satisfactory results using beds packed with cotton wool or glass fibre to achieve sterilisation of the inlet air stream.
17 For Group 2 agents, the legislative requirement is to ‘minimise the release of viable organisms’. When using pathogens with an aerosol route of infection, a user should consider prevention but, when using cell lines, minimisation is an acceptable practice. In practice this is an area of considerable variation in standard. In some applications commercial confidentiality is of the utmost importance and users prefer to prevent the release of organisms either by a 0.22 µm filter system or by incineration either of which can incidentally provide the necessary standard of safety. It must, however, be stressed that this is an optional process-based decision. The minimisation required must be calculated from the risk base of the work being undertaken. For some work it is sufficient to pass fermenter exhaust gases through an efficient cyclone separator or a spray tower where the gases will be in contact with a hypochlorite spray before being released. Whilst this can,
...... Page 73 Advisory Committee on Dangerous Pathogens ...... based on an adequate risk assessment, be acceptable for a large scale installation, smaller scale users should consider the overall cost of such a system compared with the use of cartridge filters which will provide at least the same reduction in organisms. Often in practice it is as easy and as cost effective to use a HEPA grade cartridge filter, rather than a coarser grade but without the need to install a parallel installation to ensure complete sterility at times of filter changing. For Group 3 and 4 organisms the requirement is to prevent escape. Prevention is normally achieved by HEPA filtration using 0.22 µm cartridges in a parallel installation to ensure complete downstream sterility at all times Consideration should be given to the use of two HEPA filters in series in each of the parallel legs to reduce the risk of a breach of containment due to filter failure. For the safety of engineering personnel the filter to be changed must be capable of being steam sterilised before removal.
18 Consideration should be given, depending on the foaming characteristics of the fermenter medium, to the use of antifoams, cyclone separators and impingement filters as a pre-stage in order to preserve the integrity of the cartridges. Alternatively a pre-heating stage may be placed in the exhaust air line to ensure that any water vapour droplets are evaporated, thus presenting the filter only with the gaseous phase. It may also be considered good practice to install hydrophobic and hydrophilic filters in series to present an effective filtration surface under all conditions of fermenter air discharge.
19 For process sterility it is essential to operate fermenters at a positive pressure to their immediate surroundings. Normally a differential of up to 0.5 bar is accepted practice. The pressure differential should be monitored and alarmed. Attention must be directed to small fermenters operating with Group 2 organisms where addition lines may be of plastic rather than stainless steel. These lines, which may contain acid or alkali for pH adjustment could constitute a hazard if they or their connections were subjected to a positive pressure. In these cases fermentation must be carried out at as near as possible atmospheric conditions. Operations at Groups 3 and 4 should always use stainless steel addition lines.
20 The inoculation of seed vessels is normally carried out using a closed system blow-over technique with a stainless steel transfer vessel which is filled inside a microbiological safety cabinet. For small scale work at Group 2 inoculation of seed vessels can take place using direct injection with a sterile needle/septum technique. Sterile needle/septum techniques are not acceptable for Groups 3 and 4.
21 Aseptic sampling is usually arranged by steaming the sampling connection, either on the downstream side of the sample valve or into the body of the valve itself when not in use. For Group 2 organisms sampling should be designed to minimise the unintentional release of organisms from the fermenter; care should be taken in the design of the receiving container not to generate aerosols. Sample containers should be of adequate size and the valve should preferably be of the diaphragm type, which can be opened gradually. Samples for Groups 3 and 4 organisms, regardless of their
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intended use, should at all times be taken using a closed, aseptic technique. Displaced gas is passed through a HEPA filter.
22 Fixed probes such as temperature or pressure transducers which, once fitted and calibrated, normally stay in the vessel wall, or retractable probes (such as dissolved oxygen and pH, the design of which allows their replacement during a fermentation) may be used in the case of Group 2 organisms. Retractable probes should not be used for Group 3 or 4 organisms. For high risk fermentations duplicate transducers represent a safe procedure when there is doubt about the reliability of the probe under process conditions.
23 In the recommendations for containment for industrial processes, Part III of Schedule 9 of COSHH specifies that bulk culture fluids should not be removed from the closed system unless the viable organisms have been inactivated. Some users may consider that the closed system only includes the fermenter and that to kill the organisms within the fermenter will damage or destroy the product or in some cases the viable organisms which may constitute the product. The requirement can be better understood if the closed system is extended to include the preliminary stages of downstream processing such as centrifugation in a solid liquid separator, cell rupture in an homogeniser and recentrifugation in a second solid, liquid stage centrifugation. The important factor is the removal of the hazard before there is loss of containment. The method of hazard removal depends on the product and whether this is contained in the cells after rupture or in the liquid components of the downstream processing stage. A 0.22 µm hydrophilic filter may be regarded as the edge of the contained system. Alternatively, if acceptable from the process viewpoint, a chemical or heat kill method may be used.
Process rooms and 24 All processes using Groups 2, 3 and 4 agents should be carried out in buildings - secondary equipment which is designed to prevent, in the case of Groups 3 and 4 agents containment and minimise in the case of Group 2 agents, release. The system should be such that the fermentation plant acts as the primary containment and that in addition the equipment is housed inside a closed building, which may be equipped with ventilation and, depending on the hazard arising from the agent, may also be fitted with air filtration. Such a building may be a designated building within an existing site which carries out other compatible work or it may be constructed as a separated part of an existing building which in itself is also carrying out other industrial processes. In this case particular care must be exercised to ensure that it is not possible in the event of an accident to contaminate another part of the building which is not equipped to deal with the agent being used. Normally the air inside the process buildings would be expected to be completely free of contamination by the biological agent which is retained by the primary fermentation containment system. In the case of Group 2 agents there is only a need to ventilate for comfort of operating personnel. Ten air changes/hour would be a recommended circulation rate. In the case of process areas designed for the
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use of Groups 3 and 4 agents, ventilation of the room space should be provided and HEPA filtration must be provided on the exhaust of Group 3 installations and on both the inlet and outlet air streams of Group 4 operations. The inlet and extractor systems should be alarmed and indicated and consideration should be given to the use of dynamically controlled variable speed fan motors to compensate for filter blocking. Great care should be exercised in the design and positioning of both inlet and exhaust air stacks to ensure that these cannot draw contaminated air into the ventilation inlets of another installation.
Access 25 It is important that access to work areas processing Groups 2, 3 and 4 agents should be restricted to those workers who have specific work to do in the area and who have received training in the operation, the engineering and the procedures to adopt when in the area. Primary restriction of entry to a production site might be the normal factory entrance, but this is not sufficient because of the presence of unauthorised people who are not aware of the precise nature of the work. Visitors who may become involved should be made fully aware of the permit-to-work system and its extension where necessary to cover themselves. It is essential to provide locked entrances to the process buildings equipped with either a card-key or digital lock entry system so that entry is restricted to only those people who have business to be there.
Signs 26 Biohazard signs should be displayed on the external sides of all doorways of buildings handling Group 3 or 4 agents.
Negative pressure 27 For rooms handling Group 2 agents there is no specific need to operate process rooms at negative pressure. Rooms which handle Groups 3 and 4 agents should always be maintained at negative pressure. Typical pressure differentials for process rooms are 10 to 70 Pascals.
28 Air locks are not required for work at Groups 2 and 3 level but air locks at a pressure negative to both the operating area and the immediate external environment are required for the use of Group 4 agents. Where air locks are provided, they should have indicators and alarms showing that the ventilation is operational. The exhaust air from air locks should be HEPA filtered.
Fumigation 29 The need for fumigation depends on the range of organisms being used and will be decided on a case by case basis. Users are reminded of the toxic dangers of using formaldehyde as a fumigant. Rooms fumigated using this material should be carefully exhausted to atmosphere and tests should be carried out before re-entry to ensure that the level of formaldehyde is reduced as far as is reasonably practical below the Maximum Exposure Limit (MEL) of 2.0 ppm or 2.5 mg m-3.
30 The difference between the two types of exposure limit defined in Regulation 2 of the COSHH Regulations must be understood. For a maximum exposure limit a residual risk may exist and the level set takes into
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account socio-economic factors. This is different from an occupational exposure standard (OES) at which there is no indication of risk to health. The type of limit set by HSE depends on the known dangers arising from a substance and, in the case of formaldehyde, only an MEL has been set (see EH40/95). Users are reminded of the incompatibility of chlorinated disinfectants with formaldehyde.
Hygiene 31 Decontamination and washing facilities must be provided for work with agents in Groups 2, 3 and 4. With Group 2 and Group 3 agents, it is recommended that the effluent from wash basins and showers should be collected and deactivated by validated methods before being discharged to the effluent system or drain. In the case of work with Group 4 agents, effluent collection and treatment is mandatory.
32 Consideration should be given to the use of foot or elbow operated taps.
33 Emergency showers should be provided in all Group 3 and 4 operations and, wherever possible, in Group 2 installations. In the event of an emergency calling for decontamination, the contaminated exterior of the protective clothing should not be washed down in the shower area but the operator should remove the contaminated clothing in the working area, calling for help if necessary; the clothing should then be bagged and subsequently autoclaved and/or incinerated, whilst the operator should then finally decontaminate under the shower. This procedure avoids or minimises the spread of infectious organisms into the shower unit and also into the waste water system. (Shower wastes should, as for wash basin wastes, be collected and deactivated before discharge.)
34 Under normal conditions, operators working in a Group 2, 3 or 4 area should never be contaminated. There is, therefore, no health and safety requirement for the provision of showers for comfort use on completion of a work period. The provision and use of such showers should be regarded as an element of a good human resource programme.
Bunding 35 Whilst there is no specific requirement, it is considered good practice for an installation operating at Group 2 to be designed to contain the entire contents of a fermenter in the event of catastrophic failure. Containment may be arranged as a bunded area below the fermenter or enlarged drain channels under the operating floor or drainage to a kill tank. In all cases it is important that, not only can the spillage contents be satisfactorily inactivated by chemical or heat treatment, but also that it is not possible to move the spillage from the containment area without a deliberate action. Besides gross spillage, provision also should be made for minor spillages resulting from, for example the breakage of glass equipment, an operating error or leakage from a pipe flange or a valve. A spillage policy should form part of the standard operating procedure of a plant operating at Group 2, 3 or 4. This policy should provide precise written guidance for several levels of spillage ranging from less than 1 litre to the entire contents of the contained system.
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For installations operating at Group 3 and 4 levels, complete containment is a necessity. There should be no drains from bunding in a Group 3 or 4 plant.
Waste disposal 36 Waste disposal from a process which uses a Group 1 organism does not present any specific problems and should be regarded as a normal industrial waste. Its discharge into a sewer, watercourse or the sea is regulated by the Control of Pollution Act 1974 and the Environmental Protection Act 1990, which amongst other things, places restraints on the hydraulic, biological and chemical load, the concentration and composition of the effluent. A consent to discharge must be obtained from the local water authority before any such discharge is made. Waste disposal from processes using Groups 2, 3 and 4 organisms all require treatment before they can be discharged to a public system using the same consent procedure and subject to the same constraints.
37 All process wastes, including laboratory, wash hand basin, shower and floor spillages, should be collected in a separate plant, where they can be inactivated by chemical or heat treatment. The contents of this plant shall not be discharged until inactivation has been validated on a batch by batch basis.
38 The plant should be constructed in such a manner that accidental discharge of the contents of the system is not possible. This is best arranged by having no discharge valves in the bottom of the waste treatment tanks and arranging discharge by deliberate pumping through lines inserted through the top of the vessels. A spillage policy for the waste treatment area must be in place just as for the process area.
Personal protection 39 Correct personal protective clothing and equipment must be provided for all personnel who enter an installation designed for operation with Groups 2, 3 or 4 agents. Attention is drawn to paragraph 9 of Schedule 9 to the COSHH Regulations which defines conditions for the storage, handling and maintenance of personal protective equipment including clothing.
40. A single piece overall or two piece suit consisting of jacket and trousers and a hat should be provided on an individual issue basis for each operator. With Group 3 and 4 operations a change of clothing should be provided on each entry into the area. Also for Group 3 and 4 agents the clothing should be autoclaved after use. Where clothing is known to have been contaminated with any organism, special care must be taken to ensure that it is placed in a sealed container before removal for autoclaving or incineration.
41 All operatives should be issued with a personal locker in which to store external clothing. For Group 2 either a separate locker should be provided for work clothing which is used on more than one occasion or adequate individual storage space should be provided external to the contained area for the storage of work clothes.
42 Personal protective equipment (PPE) may be required to protect workers from risks other than exposure to biological agents. Consideration must be
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given to the personal issue of gloves, goggles or safety spectacles, visors and respiratory protective equipment (see Appendix 10), safety shoes and safety hats or helmets. The need for such PPE should form part of the risk assessment under COSHH. In the case of a microbiological hazard, emergency personnel should be issued with a self-contained plastic suit before entry to the contained area.
43 No eating, drinking, smoking, taking of medication, storage of food or application of cosmetics should be allowed in any area which processes Group 2, 3 or 4 agents or in the downstream processing plant associated with such work. Rest areas should be specifically provided for such purposes. lmmunisation 44 Subject to assessment of risk, vaccines should be made available for those employees who are not already immune to the biological agents to which they are exposed or are liable to be exposed.
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APPENDIX 7 IMMUNISATION
1 Paragraph 6 of Schedule 9 in the COSHH Regulations 1994 specifies that if assessment reveals that there is a risk to the health and safety of workers due to their exposure to biological agents for which effective vaccines exist, such vaccines should be made available unless workers are already immune.
2 Those accepting vaccination should be informed of the benefits and drawbacks of both vaccination and non-vaccination. The Health and Safety at Work Act provides for vaccination to be offered free of charge to workers. A vaccination record should be kept which should be made available to the worker in question on request.
3 Effective vaccines are available for the following agents and vaccination is recommended for those who may be exposed to infection in the course of their work.
Bacteria Bacillus anthracis Bordetella pertussis Clostridium tetani Corynebacterium diphtheriae Francisella tularensis (type A) Mycobacterium africanum Mycobacterium bovis (excluding BCG) Mycobacterium leprae Mycobacterium tuberculosis Neisseria meningitidis (groups A & C) Salmonella typhi Yersinia pestis
Viruses Absettarov virus Hanzalova virus Hepatitis A virus Hepatitis B virus Hepatitis D virus (HBV vaccine) Hypr virus Kyasanur Forest disease virus Louping ill virus Measles virus Mumps virus Monkeypox virus Variola (and ‘whitepox’ virus) Omsk virus Polio virus types 1, 2 and 3. Rabies virus Rift Valley fever virus Rubella virus Western European tick-borne encephalitis viruses
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Eastern equine encephalomyelitis virus Western equine encephalomyelitis virus Venezuelan equine encephalomyelitis virus Japanese B encephalitis virus Russian spring-summer encephalitis virus Yellow fever virus Influenza A and B viruses
Vaccinia 4 The ACDP, jointly with the Advisory Committee on Genetic Modification, has prepared specific guidance (see Appendix 18) on formulating local policies on immunisation for those working with vaccinia virus, its recombinants or related pox viruses.
Guidance on 5 Information and advice about vaccines and immunisation procedures immunisation and prepared by the Joint Committee on Vaccination and Immunisation, (JCVI) is supply of vaccines published periodically in lmmunisation against infectious diseases by the Department of Health, Welsh Office and Scottish Home and Health Department. Sources of supply of the vaccines considered by the JCVI are included. Information on other vaccines, immunoglobulins and antitoxins can be obtained from the Department of Health, Medical Devices Agency.
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APPENDIX 8 MICROBIOLOGICAL SAFETY CABINETS
1 A microbiological safety cabinet (MSC) is a device intended to offer protection to the user and the environment from airborne droplets or particles generated in handling infected and other hazardous biological material. Air discharged from an MSC to the atmosphere is always to be filtered. Two of the three types of cabinet specified in BS:5726: 1992 (see paragraphs 2, 3 and 4) also provide protection against contamination of the product manipulated in them. An MSC is not designed to contain radioactive, toxic or corrosive substances. (See also below under Laminar flow cabinets.)
2 This Appendix merely provides a brief summary of the essentials of the design, function and operation of MSC. Reference should be made to British Standard 5726: 1992 Microbiological Safety Cabinets, for a full description of the three types of safety cabinet, Class I, Class II and Class III. The Standard also describes the methods for testing air velocity, filtration efficiency and for determining the level of protection provided by them.
British Standard 3 BS 5726: 1992 is divided into four parts. 5726:1992 Part 1: specification for design, construction and performance prior to installation:
Part 2: recommendations for information to be exchanged between purchaser, vendor and installer and recommendations for installation:
Part 3: specification for performance after installation;
Part 4: recommendations for selection, use and maintenance.
4 Parts 1 and the 3 are mandatory if a safety cabinet and its installation are to meet the detailed requirements of the Standard while Parts 2 and 4 offer useful practical recommendations for safe use. Regulatory authorities may make use of all four parts of the Standard in defining safe working practices recognising that alternative equipment and procedures may be acceptable if they provide an equivalent degree of protection.
Mode of operation - 5 A Class I MSC is designed to provide operator protection by maintaining Classes I, II and Ill an inward flow of air past the operator and over the work surface inside the cabinet. As the incoming air is unfiltered, this type of cabinet does not provide product protection. There is a risk that cell cultures, for example, will become contaminated by airborne organisms in the working environment. Class II cabinets, on the other hand, offer protection to both the operator and the product. The inflow of air at the front of the cabinet, which is filtered before circulation within it, discourages emission of airborne particles generated by the work while the downflow of filtered air over the working surface protects the work. In this model, of which there are two types, the design also allows for protection against cross contamination within the cabinet.
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6 Class III cabinets (often erroneously called ‘glove boxes’1) are totally enclosed units and can provide the maximum protection for the operator, the environment and the work. In this model, both incoming and outgoing air is filtered. Access to the interior of a Class III cabinet is gained by use of arm- length gloves attached to ports in the front panel of the unit. Use of Class Ill cabinets is generally confined to work with pathogens in Hazard Group 4 but this model may also be appropriate for other work where the equipment or procedures used may present a risk of vigorous aerosol generation.
7 The minimum inward airflow through the front aperture of a Class I or Operator protection Class II cabinet is defined in BS:5726. This is necessary to provide factor containment and is related to the ‘operator protection factor’ (OPF) for which the minimum is 1.0 x 105. That figure expresses the ratio of the number of airborne particles that would be generated in a procedure conducted on the open bench and the number liberated from the working aperture of a cabinet in which there is the same level dispersal. This means that for every 100 000 particles used in a test as a challenge to the inward flow of air at the working aperture, not more than one should escape. The conditions for conducting the test of OPF are defined precisely in the Standard.
8 Air discharged from all three types of cabinet is filtered before being Filters discharged to atmosphere. MSC constructed in accordance with BS: 5726 1992 are required to have high levels of filtration efficiency and this is achieved through use of ‘HEPA’ filters (High Efficiency Particulate Absorption). These are usually made of fan-folded glass-fibre paper with a filtration efficiency of 99.997% when tested by the manufacturer in accordance with BS:3928. In effect, this means that for every 100 000 challenge particles generated in a test of a filter and its seal, no more than three should penetrate.
9 Cabinets should be purchased from a manufacturer or supplier who can Selection show ‘type test’ certification as required in Part I of BS: 5726 and buyers should be certain to choose a cabinet appropriate for the work. Class I and II cabinets must not be used at Containment Level 4 and, in general, Class II cabinets should not be used for work with agents in Hazard Group 3.
10 Before a Class II cabinet is selected, the user should consider the agent to be handled, assess the need for protection of the work and relate this to the OPF that can be achieved in the intended conditions of use. Modern Class II cabinets made to the British Standard will provide a protection factor of the same order as Class I cabinets (ie a factor of 1 x 105 or better) under the test conditions prescribed in the Standard. However, in day-to-day working conditions, a Class II cabinet is potentially more susceptible to disruption of its
1 A ‘glove box’ is simply a box (usually made of transparent plastic or with a plastic or glass window) with gloves attached but not necessarily with any through-put of air filtered or unfiltered. Glove boxes are a primitive form of containment and are not generally suitable for handling infectious materials.
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airflow pattern than is a Class I cabinet. If it can be shown that the required level of operator protection is achieved consistently (as demonstrated by in- use tests - see Note 1) and provided that the local safety management will allow, a Class II cabinet may be used for some work with certain Hazard Group 3 pathogens where protection of the work is essential.
Installation 11 The cabinet installer should discuss siting with the customer to ensure that the optimum position is chosen consistent with maintaining the required level of safe performance. Factors to be considered are the proximity of the cabinet to doors, windows, ventilation ducts and to movement routes. Once installed, commissioning tests should be conducted to ensure that the safety performance matches that prescribed in BS5726 and, where appropriate, the standards for product and cross contamination protection.
12 The importance of these commissioning tests cannot be over- emphasised. They combine examination of the cabinet’s performance and the effects of environmental conditions to demonstrate the level of protection likely to be achieved in practice. When equipment or procedures are being used which might affect the degree of operator protection, appropriate ‘in-use’ tests should be devised. Safety cabinet containment is sometimes adversely affected by, for example air pressure changes in exhaust ducts and by electrical and/or mechanical problems with control systems where the cabinet exhaust and laboratory ventilation are interlinked. Such difficulties may be overcome by recycling cabinet exhaust air to the laboratory. Because the position of a safety cabinet in a laboratory can be most important in maintaining safe performance, cabinets that recirculate air should not be regarded as portable. For this reason, fitting wheels or castors to such cabinets should be strongly discouraged.
Discharge of air from 13 BS 5726 requires that safety cabinets be constructed so as to: safety cabinets (a) exhaust the discharged air to the outside by a dedicated extract system: or
(b) recycle discharged air back into the laboratory through two exhaust filters (in such cases the two filters and their seals must be tested independently).
14 Option (a) above is the preferred method. With recirculation (option (b)) there can be problems in, for example, fumigating the cabinet and clearing the fumigant before changing filters etc. Work at Containment Level 2 does not necessarily demand double HEPA filtration but while filtration efficiency is certainly raised by the use of double filters, the requirement is not so much for this as in providing a ‘fail-safe’ system in which one filter would compensate for a fault in the other or the seal around it.
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15 The choice between total exhaust or recirculation for a particular installation will depend on assessment of local conditions. Recirculation would be inappropriate if a gas or vapour phase of contamination was released in the work process unless, for example, some form of monitored charcoal absorption system was used on the exhaust line.
16 For cabinets that recycle filtered air to the laboratory, it is important to consider in advance safe methods for conducting away fumigant when the cabinet is to be decontaminated. Suitable methods include the use of temporary ducting connected to the air outlet and leading to a fume cupboard.
Use of safety cabinets 17 The inward airflow to an MSC, which is drawn through the working aperture of open-front cabinets (Class I and Class II), can be disturbed by, for example, sudden movement of the arms of the operator and turbulence in and around the equipment placed inside the cabinet. A centrifuge, for example, should never be placed inside a MSC unless it is a totally enclosed Class III cabinet. People moving in the vicinity of the cabinet, air movements in the room or changes in air pressure (for example when a door is opened) can also influence its performance. Disturbances of this kind may significantly affect the level of protection for the operator, particularly when a Class II cabinet is used, because this type generally has a lower inward air velocity through the upper part of the working aperture.
18 Users of safety cabinets must be made fully aware of these limitations and of the way in which safety cabinets operate. More detailed advice on these factors is given in Part 4 of the British Standard.
Maintenance and 19 Regulation 9 of the COSHH Regulations in referring to ‘local exhaust testing of safety ventilation’, requires a thorough examination and testing of safety cabinet cabinets installations to be carried out at intervals not exceeding 14 months. To achieve best practice it is recommended that the procedures in Part 4 of BS 5726 1992 are followed.
20 In some cases, depending on the frequency of use, regulatory authorities may require a cabinet to be tested at more frequent intervals, for example, six monthly in the case of some Containment Level 3 and Containment Level 4 laboratories in order to verify the quality of containment systems in use for a particularly potent pathogen.
21 Fumigation and decontamination of cabinet installations is required before maintenance engineers are allowed to work on the equipment. Part 4 of BS 5726 1992 gives guidance on suitable decontamination procedures (see also Appendix 9).
22 Although planned maintenance and other checks are a requirement, it will be necessary also to carry out thorough inspection and testing when changes
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have been made that may affect containment performance. If, for example, a cabinet is moved to a new position in the laboratory, full commissioning tests will be needed. Other changes such as placing equipment around or near the cabinet may require less stringent checks.
Laminar flow cabinets 23 So-called ‘laminar flow’ cabinets are NOT microbiological safety cabinets and should never be used when handling infectious or potentially infectious materials. Laminar flow cabinets are designed to deliver a stream of HEPA- filtered air across (‘horizontal laminar flow’) or down onto (‘vertical laminar flow’) a working surface so as to provide an environment in which sterile materials such as culture media, drug preparations do not become contaminated. Their mode of operation is such that any airborne droplets generated in, for example, pipetting and similar manipulations are actively directed at the operator. The use of laminar flow cabinets with any material infectious or potentially infectious for humans is therefore positively hazardous.
Notes 1 The in-use test referred to is the operator protection factor measured according to the procedure in BS5726, but with the artificial arm removed. In its place, an operator works with hands and arms within the cabinet throughout the test, and performs, for example, typical repetitive pipetting procedures. Other in-use tests may also be necessary, based on the actual conditions and work practices of individual laboratories.
2 Advice on technical matters and the supply of microbiological safety cabinets can be obtained from Department of Health (DH) Medical Devices Agency, 14 Russell Square, London WC1B 5EP, and on installment from NHS Estates Department of Health 1, Trevelyan Square, Boar Lane, Leeds LS1 6AE. Advice on these issues may be also obtained: in Scotland, from the Supplies Division of the Common Services Agency, Trinity Park House, South Trinity Road, Edinburgh EH5 3SH; in Wales, the Welsh Office, Cathays Park, Cardiff CF1 3NQ; and in Northern Ireland, from the Department of Health and Social Services Dundonald House, Upper Newtonards Road, Belfast BT4 3SF. Guidance on technical issues and the use of safety cabinets is available from the Health and Safety Executive, Technology and Health Sciences Division, Magdalen House, Stanley Precinct, Bootle, Merseyside, L20 3QZ.
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APPENDIX 9 FUMIGATION
1 On occasions it will be necessary to decontaminate laboratories, animal containment facilities and safety cabinets by fumigation when, for example, there has been a spillage of infectious material or when servicing or maintenance work is to be carried out. Fumigation should always be a planned exercise with appropriate controls in place and with information and warnings provided for those who need to know. Fumigation operations should only be carried out by named, trained personnel working to an agreed plan and using a method that is known to be effective in the circumstances of use.
Fumigant 2 Formaldehyde vapour, which has been known for many years as a highly effective biocidal agent, is the fumigant most commonly used in laboratories. There is more than one way of generating formaldehyde but the usual source is formalin which is readily available as a 40% solution of formaldehyde vapour in water. When heat is applied, the vapour is generated in quantity. (See Notes 1 and 2.)
3 For formaldehyde to act to maximum effect, it must be able to penetrate (hence pre-cleaning is helpful if it can be done without jeopardising safety) and, it must be able to dissolve at adequate concentrations in the film of moisture in the immediate vicinity of the organisms to be inactivated. Water vapour generated in the process of dispersing formaldehyde (see paragraph 4) provides the essential optimum level of relative humidity (ie greater than 35% but less than 80%). Too much formaldehyde results in the deposition of sticky deposits of paraformaldehyde.
4 There are a number of methods of generating formaldehyde vapour:
(a) heating a mixture of formalin and water in a thermostatically controlled heating unit (such as an electric frying pan or electric kettle);
(b) mixing formalin and water with potassium permanganate crystals*;
(c) using commercially available formaldehyde generating kits; and,
(d) heating formalin in a purpose-made vapourising unit (safety cabinets).
* WARNING: the correct relative concentration of these two components is essential to avoid a violent reaction
Fumigation of 5 Microbiological safety cabinets should always be fumigated if a large microbiological safety spillage of infectious material occurs within them, before filters are changed or cabinets any maintenance work is carried out which involves gaining access to the interior of the cabinet (for example air ducts). Fumigant should be generated
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with the night door securely sealed and the non-return valve left closed. Passive migration of the fumigant through the filter can occur but an alternative is to leave the valve open and the fan running for 10 to 15 seconds to ensure penetration of the filter medium. The valve should then be closed and the fan switched off while the remainder of the fumigant is left to disperse within the cabinet. After at least six hours, or preferably overnight, the fumigant should be exhausted to atmosphere by switching on the fan and allowing air from the room to enter the cabinet (for example through a large bung-hole in the night door). Before venting the formaldehyde in this way, it is essential to ensure that no-one is in the vicinity of the exhaust outlet and that the exhaust air does not enter nearby windows or ventilation air intakes. If filters are to be changed after fumigation, the discarded filter unit should be bagged and autoclaved before disposal. There are special difficulties if the cabinet is used with the agents causing transmissible spongiform encephalopathies as they are resistant to inactivation by formalin (see Appendix 19). More detailed advice on the fumigation of safety cabinets is given in Part 4 of British Standard 5726:1992
Fumigation of rooms 6 When a room in a laboratory or animal containment unit is to be fumigated, the area should be checked to ensure that it is securely sealed so as not to allow the escape of fumigant to other parts of the building. Suspended ceilings can present a special difficulty as there may be a void above connecting with other rooms nearby.
7 It should be noted that any hydrochloric acid and chlorinated disinfectants should, if possible, be removed from the room before fumigating with formaldehyde. This is to prevent the possibility of forming bis (chlormethyl) ether which may be carcinogenic.
8 A test of the effectiveness of the fumigation may be carried out by placing spore strips/discs carrying Bacillus subtilis var globigii (filter paper inoculated with a suspension of the organism) at various points in the room to test penetration of the fumigant. Similarly, a standardised spore suspension may be painted onto small marked areas on surfaces which are later swabbed to recover any surviving organisms.
9 Exposure to the residual effect of the fumigant after generation should be for at least six hours or preferably overnight. Fumigant may be extracted from the area by the air handling system but only when that is a total loss system with no possibility of formaldehyde vapour being conducted to other areas. More commonly, use is made of a microbiological safety cabinet or a fume cupboard as a means of extraction if one is situated within the area under treatment and if it exhausts to atmosphere. In all cases, the plant or equipment extracting the air should be operated by an external switch so as to avoid entering the room.
10 After the fumigant has been evacuated in this way, there should be a thorough check of the level of residual vapour before anyone enters. This
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may be done most conveniently by, for example, sampling the air through a small port fitted in the door for this purpose. Meters and other assay devices are available to indicate the concentration of formaldehyde vapour remaining in the air. (See Note 1.)
11 A number of factors affect the efficiency of fumigation. The ratio of formalin to water used and thereby the relative humidity created, the volume of the space to be fumigated, the surface area exposed in that space and the presence of absorbent materials such as cardboard boxes. At temperatures below 18°C formaldedehyde fumigation is less effective. Below 9°C, formaldehyde sublimes and is less easy to vapourise.
12 Personnel should not enter an area when a major spillage of micro- organisms has taken place as there may be a great risk of exposure to infection by organisms that may remain suspended in the air for some time. Moreover, personnel should not enter an area when the fumigant has been generated except in a dire emergency when full breathing apparatus which provides air from an independent source must be worn. Only those trained in the use of breathing apparatus should use it. Respirators are not appropriate for use in the concentrations of formaldehyde vapour achieved when carrying out these procedures.
13 In case of difficulty, HSE’s Technology and Health Sciences Division (Magdalen House, Stanley Precinct, Bootle, Merseyside) is able to provide advice on fumigation.
Notes 1 Formaldehyde is a Schedule 1 chemical under the COSHH Regulations and has a Maximum Exposure Limit (MEL) of 2 ppm or 2.5 mg m-3.
2 Formaldehyde vapour is explosive at 7.75% in dry air. Its ignition point is 430°C
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APPENDIX 10 RESPIRATORY PROTECTIVE EQUIPMENT
1 The use of the procedural and engineering control measures described in the text on containment are the preferred methods of preventing or, where this is not reasonably practicable, adequately controlling exposure to biological agents. Containment at source should be the primary aim but when it is necessary to use respiratory protective equipment (RPE), the employer must ensure that the equipment used is suitable for the work undertaken.
2 RPE is not specifically approved by HSE for work involving exposure to infection. Approval by HSE shows only that RPE has met the performance requirements of an approved standard or test protocol. It is not a guarantee that the RPE will provide appropriate control in every circumstance. However, RPE approved for use in other work situations may be suitable. In order to determine whether such equipment is capable of providing adequate protection, an assessment should be made of its performance in relation to conditions in the workplace. Performance data, including filter efficiency and face-seal leakage, should be obtained from the manufacturer. Such data must include the results of biological tests (for example using spores of Bacillus subtilis var globigii NCTC 10073) or conventional physico-chemical tests (for example using a sodium chloride aerosol). For low performance equipment such as disposable and some half mask respirators, it has been shown that sodium chloride aerosol is an effective indicator of performance in relation to biological aerosols.
3 There is a large variety of RPE available, including the ‘high efficiency’ type with improved filter performance and ‘positive pressure’ equipment (full face mask and half suits/blouses), that does not place the same reliance on face- seal integrity as the ‘negative pressure’ type. Selection of RPE should include an assessment of the ease of use and maintenance in addition to whether it is capable of adequately controlling exposure.
4 The employer must ensure that suitable training on the fitting and use of RPE is given to all people who need to wear such equipment. Instruction on disinfection and routine maintenance after use should also be provided. COSHH Schedule 9 at paragraph 9 shows that RPE must be checked and cleaned at suitable intervals to ensure that it is maintained in good repair and efficient working order. Defective items must be replaced. A record or suitable summary thereof of examinations, tests and repairs of RPE must be kept for at least five years.
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APPENDIX 11 SAFE DISPOSAL OF WASTE
1 All forms of waste are categorised in law and there is specific legislation for the provision of means for the safe storage and disposal of substances hazardous to health. A biological agent (and thereby anything contaminated by a biological agent) which creates a hazard to the health of any person is a substance hazardous to health.
2 As such, waste consisting of, for example, discarded cultures and associated items and infected animal carcasses is ‘controlled waste’ and subject to segregation, collection and transport regulations. Although EC regulations or Directives on hazardous waste may affect legislation in the future, current regulations define clinical waste as an ‘industrial waste’ and place it in the category of controlled waste. The onus is solely on the producer of waste to ensure its safe collection and disposal.
3 Under the Environmental Protection Act - the Controlled Waste Regulations 1992 define ‘clinical waste’ as:
(a) ‘any waste which consists wholly or partly of human or animal tissue, blood or other body fluids, excretions, drugs or other pharmaceutical products, swabs or dressings, or syringes, needles or other sharp instruments, being waste which unless rendered safe may prove hazardous to any person coming into contact with it’; and,
(b) ‘any other waste arising from medical, nursing, dental, veterinary, pharmaceutical or similar practice, investigation, treatment, care, teaching or research, or the collection of blood for transfusion, being waste which may cause infection to any person coming into contact with it’.
4 There are a few categories of establishment where some of such waste would be regarded as household waste. Nevertheless, clinical waste remains clinical waste wherever it is produced and should be handled with care. Unless treated under controlled conditions that ensure its being rendered free from hazard, it is essential that it is handled in a secure manner to avoid risks of infection for those coming into contact with it.
5 There is a duty in law for people producing clinical waste to take reasonable steps to handle and look after it safely and ensure its legal disposal by others. They must ensure that the waste is handled and stored safely and securely and that the transfer of waste for treatment or disposal is made only to an authorised person together with a written description of the waste in a transfer note. There is a duty for the producer of the waste to ensure that carriers hold the appropriate registration and/or licences to dispose of that type of waste.
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Clinical laboratory 6 Waste generated by clinical laboratories differs from other clinical waste waste in that it may be expected to contain large numbers of pathogenic organisms and sharp objects whether infected or not, and may contain visually obnoxious materials such as tissue and blood.
7 The Health and Safety Commission in the document The safe disposal of clinical waste, 1992, in agreement with the guidance of the ACDP, states:
All infected waste arising from work in laboratories should be made safe to hand/e, ideally by autoclaving, before disposal by incineration. If it is not reasonably practicable to autoclave waste, it should be disposed of by incineration. It is essential that this waste is secured in strong, leak-proof containers and transported direct/y to the incinerator.
8 It is also recommended that all infected waste from microbiological laboratories, and microbiological cultures from other laboratories, should be autoclaved before disposal by incineration.
Final disposal of 9 Disposal of clinical waste by landfill may not always be acceptable1 clinical waste unless first rendered safe. All clinical wastes in paragraph 3(a) and (b) above must be incinerated. Waste producers should consult waste collection and/or clinical waste disposal authorities who will be found through Local Authority offices2. Similarly, new restrictions on the operation of incinerators may demand the use of licensed contractors.
Disposal of human 10 Human tissues and animal carcasses and tissues arising from hospitals tissues and animal veterinary centres, or laboratories are classified as clinical waste Group A carcasses (see Safe disposal of clinical waste 1992, Health and Safety Commission, Health Services Advisory Committee).
11 COSHH does not require there to be an incinerator on site for the disposal of carcasses infected with biological agents in Groups 2 and 3 but one must be accessible. This means that carcasses may be transported to another site for final disposal. If this option is adopted, it is essential that a suitable form of packaging is used both to protect handlers and transporters against infection and to avoid public offence. In some cases it may be necessary to consult agriculture departments before carcasses infected with animal pathogens are moved and where appropriate movement must comply with the Animal By-Products Order 1992.
12 Infected material should be placed in yellow waste sacks. They should then be suitably labelled (permanent marker or tie-on label) showing the source of the material. Sacks should be no more than three-quarters full and should be closed with purpose-made plastic ties or closures or, in the case of light-gauge sacks, may be tied off at the neck. Heat-sealers purpose-made for clinical waste may also be used. Sacks should then be stored and transported in a robust secondary container which is leakproof and which may be readily decontaminated. 1 Waste Management Paper No 25, Clinical Waste DoE 1993. 2 Environmental Protection Act 1990:Waste Management: the duty of care, a Code of Practice 1991 HMSO ISBN 0 11 752557 X...... Page 92 Advisory Committee on Dangerous Pathogens ......
13 Another method of transporting animal carcasses which is recommended where the material concerned presents a higher risk (for example material from Animal Containment Levels 3 and 4), lies in the use of purpose-made plastic disposal containers. These are hermetically-sealable with snap-on lids and are designed for safe transportation and incineration in entirety. After sealing, the container should be externally decontaminated and labelled before removal to the incinerator. It is advisable to use only containers of this type which conform with drop-tests and leak tests defined, for example, by the United Nations.
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APPENDIX 12 CONSIGNMENT OF INFECTIOUS MATERIAL BY POST
1 Most biological agents and pathological specimens may be sent by post provided that the conditions required by the Post Office are met. The exceptions are those agents in Part V of Schedule 9 of the COSHH Regulations (all viruses in Hazard Group 4 and specified viruses in Hazard Group 3 - see Appendix 22).
2 Reference should be made to the current edition of the Post Office Guide for details on the consignment of infectious materials by post.
3 Briefly, the Post Office requires that:
(a) only First Class letter post or Datapost is used;
(b) exclusive use is made of the range of packaging types acceptable to the Post Office;
(c) every specimen is contained in a primary container hermetically sealed or otherwise securely closed;
(d) the capacity of the primary container for any one specimen does not exceed 50 ml (although multiple specimen packs are acceptable provided that each container is separated from the next by soft absorbent material to prevent contact);
(e) the primary container is wrapped in sufficient absorbent material to absorb all possible leakage in the event of damage and sealed in a leakproof bag.
4 This primary packaging must then be placed in one of several alternative types of outer packing specified in the Post Office Guide. The outer cover or wrapping must be conspicuously labelled ‘Pathological specimen - fragile with care’ and show the name and address of the sender.
5 Guidance for clinical laboratories from the Health Services Advisory Committee1 recommends that where it is known or suspected that the material may contain a Hazard Group 3 agent, then the innerwrapping should bear a ‘danger of infection’ label to alert staff in the receiving laboratory.
6 Pathological specimens may not be sent by post by members of the public unless it is at the specific request of a qualified medical practitioner or a registered dental practitioner or a veterinary surgeon or a registered nurse or a recognised laboratory or institution. In each case, the person or organisation making the request must supply the approved or specified packaging and clear instructions on its use.
1 see Safety in health service laboratories: Safe working and the prevention of infection in clinical laboratories 1992 Health and Safety Commission, Health Services Advisory Committee ...... HSE Books 0 11 885446 1 Page 94 Advisory Committee on Dangerous Pathogens ......
APPENDIX 13 THE HAZARDS OF CELL CULTURES
Introduction 1 The term ‘cell culture’ is defined in the COSHH Regulations as ‘.. the in vitro growth of cells derived from multicellular organisms..‘, and as used in this Appendix, refers to primary cell cultures (ie cells proliferating directly from freshly disaggregated tissue or derived from body fluids), finite cell strains and continuous cell lines.
2 Cell cultures may be vehicles for the transmission of infectious agents but they are included in the definition of ‘biological agent’ in the COSHH Regulations in recognition of the fact that they may be hazardous in other ways.
3 Uncontaminated cell cultures do not generally appear to present a significant hazard and even direct dermal inoculation may result only in local inflammation. However, a key factor is that they are proliferating systems that can sustain the survival of and/or the replication of a range of adventitious agents. Of these, those most likely to occur are viruses but several other potential hazards should be considered. These relate to components of the cell culture medium, other adventitious agents (for example contaminating mycoplasmas) and cell products some of which may be biologically active molecules with pharmacological, immunomodulating or sensitising properties.
Risk assessment 4 It is essential that all cell cultures in use should be included in the risk assessment required by COSHH. A variety of sources of information should be used including the supplier, the originator of the cell culture (if not the same as the supplier) and literature searches based on the claimed identity of the cells. True identity cannot always be assumed as there are numerous reports of cross-contamination in which the original cell line had become overgrown by another contaminating cell type. Thus, it is important to use only cell strains and cell lines that have been authenticated and have a documented provenance. These are best obtained from the originator of the cell culture or a culture collection1.
5 The level of risk presented by cell cultures varies. Factors to be considered are their anatomical and species origin which are directly related to the potential for infection by viruses or other agents pathogenic for humans. Laboratory workers should not cultivate their own cells as in vitro transformation or genetic modification could result in malignant disease or expression of an unusual pharmacologically active protein if they were to be accidentally inoculated into the donor. Human cells for culture should therefore be obtained only from individuals having no association with the experimental work.
6 The cell cultures of highest risk are likely to be those of human and primate origin especially those derived from peripheral blood, lymphoid cells and neural tissues.Where infection with an agent pathogenic for humans is known or is suspected, cell cultures should be handled at a containment level
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appropriate to the agent concerned. To simplify the risk assessment, cell cultures may be allocated to one of several groups.
7 Additional hazards from cell cultures relate to the generation and use of modified cells, for example, hybrids, transformed cells and cells containing recombinant DNA. These include the appearance of modified or reactivated viruses, novel fusion/hybrid proteins (especially in cross-species hybrids) and the expression of viral or cellular oncogenes.
Risks from cell culture 8 In handling cell cultures, rapid pipetting, scraping and pouring should be procedures avoided to limit the risk of exposure to aerosols or splashes. Sharps should not be used where there is a reasonable alternative. As with all work with infectious or potentially infectious material, microbiological safety cabinets should be used and these must be correctly installed, maintained and regularly tested (see Appendix 8).
9 The level of production of any virus present in a cell culture system will be dependent on the culture conditions and therefore careful assessment should be made of any proposed changes such as in the composition of the culture medium, the incubation temperature and the frequency of subculturing. The appearance of an unexpected change in cell phenotype (for example syncytial formation) or of inclusion bodies or viral particles indicates the need for re-assessment before work continues. When cells have been harvested and treated for a preparative procedure the material may still remain infectious. The likelihood of infectious agents persisting in any product from a cell culture may be assessed by ‘spiking’ experiments using representative contaminants deliberately introduced so to allow checks to be made at different stages in the preparation procedure. Some cell products may be allergenic and this will require stringent primary containment and/or personal protection for the operators to prevent inhalation or contact with mucous membranes.
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Containment 10 As indicated in the table, where there is evidence or suspicion of the presence of a pathogen (for example Herpesvirus simiae in simian tissues or HIV in human peripheral white blood cells), cell cultures must be handled at the level of containment demanded for the pathogen in question. All procedures involving propagation of cell cultures that are infected or are otherwise hazardous should be conducted at a minimum of Containment Level 2 with all manipulations performed in a microbiological safety cabinet. Where only small numbers of cells of low risk of infection and in a non- proliferating state are used, a safety cabinet may not be necessary. Conversely, where the volume and number of cells is high (for example large- scale cultures in single large vessels), or where the level of exposure is increased because of unavoidable production of aerosols, then containment conditions and accident contingency plans should be upgraded.
Disinfection and 11 An effective decontamination policy is required for all materials used in waste disposal association with cell cultures and discarded cell culture fluids. Decontamination procedures should be capable of inactivating viruses and other contaminating agents in the presence of fluids that are often heavily loaded with organic material. Chemical decontamination is likely to be less satisfactory than heat because of this. The risk of infection at the various stages of disposal should be assessed and appropriate measures taken.
Conclusion 12 Adequate assessment based on an awareness of the hazards, good organisation of work and adherence to principles of good laboratory practice are critical to the safe use of cell cultures. It is important that basic quarantine and segregation procedures are adopted to prevent the inadvertent transmission of infectious agents from one culture to another. To guard against this and to avoid the contamination of cells by other types of cell, only one cell line should be handled at a time with appropriate decontamination methods used between operations on different cell types. It is also desirable that cell cultures that are known to be infected are handled at the end of the work period or preferably in a different laboratory from those that are known to be infection-free.
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APPENDIX 14 Persistent infections in animals
1 Human contact with animals in the workplace may take place with animals bred in approved breeding units in the UK, imported from abroad or brought in from the wild. These animals undergo procedures ranging from simple husbandry to invasive surgery for experimental and therapeutic reasons. The excreta, blood and body fluids of animals may contaminate the worker by direct contact with skin, mucous membranes, aerosols, direct inoculation by sharps used in a procedure or by a bite. This Appendix considers the risk to humans at work from animals carrying persistent infections but showing no overt signs of the disease.
2 The chance that an animal or group of animals in a laboratory is infected is dependent on its origin. Stock supplied by approved breeding units are most unlikely to harbour a persistent infection when compared with animals imported from the wild. If animals are infected, for example, with lymphocytic choriomeningitis virus (mice) or Herpesvirus simiae (B virus of monkeys) the agent may be present in a latent non-infectious form which is only reactivated by little understood mechanisms. As a result, they may become infectious for those working with them.
3 It is not possible to screen all animals for all persistent infections because, as the recent outbreaks of Muerto Canyon (now known as Sin Nombre) disease in the USA suggest, an unknown number of these infections remain to be discovered. Despite the small chance of being infected by an animal with a persistent infection, assuming due care and precautions have been taken, if it does happen the consequences are often serious and can result in a high mortality and morbidity. Where doubt exists it is therefore essential that precautions are taken: to protect the worker by housing animals in at least Containment Level 2 accommodation; by wearing appropriate protective clothing; by reducing aerosol generation; by minimising the use of sharps; and being aware of the likely hazards associated with the species and the early symptomatology of the commoner persistent infections that they suffer. Some examples of these are given below.
Hantaviruses 4 Hantaviruses and related viruses are agents of human disease collectively known as haemorrhagic fever with renal syndrome (HFRS). The viruses are recognised in China, Korea, the CIS, the USA, Scandinavia, Northern and Southern Europe. The world-wide distribution probably results from their association with rodent species. Novel hantaviruses that produce haemorrhagic fever with pulmonary complications have recently been isolated in the south western United States of America (Sin Nombre, formerly known as Muerto Canyon).
5 Hantaviruses cause persistent asymptomatic infection within their natural rodent hosts Human infections arise from close contact with rodents and for Korean haemorrhagic fever virus, mortality rates as high as 10% have been
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recorded. Human infection is probably acquired from aerosolised urine or other excreta, the same mechanism by which rodent-to-rodent transmission is assumed to occur. Human-to-human transmission does not appear to be a feature of these infections.
6 Laboratory infections have been recorded amongst research workers exposed in the laboratory to wild rodents collected in epidemic areas. Because of the increased identification of hantaviruses in rodents worldwide it is recommended that only serologically negative animals are used for laboratory work. These are available from all reputable suppliers.
7 Hantavirus antibodies have been detected in sera from Somerset farm and sewage workers with acute illness. Limited serological evidence suggests the source was rats or other small rodents. In Northern Ireland seropositive rates as high as 25% have been recorded in field and house mice with serological evidence of sub-clinical infections in humans. There have been no recorded fatalities from hantavirus infection of UK origin.
Tick-borne encephalitis 8 Tick-borne encephalitis (TBE) and related viruses are found throughout and related viruses Europe and Asia. These viruses may be transmitted by infected ticks to humans when the ticks take a blood meal. Mortality rates of at least 1% are recognised. TBE viruses have been isolated from healthy small rodents in Slovakia at times when ticks were not considered to be active. The infected animals tested seropositive for TBE virus. It is assumed that the animals are persistently infected. Wild rodents imported from European countries in which TBE is known to be prevalent should be assumed to be a potential source of these viruses and handled accordingly. It is unlikely that rodents from approved breeding units would carry TBE or related viruses.
Borreliosis 9 Borrelia burgdorferi is the etiological agent of Lyme disease and is transmitted by the tick Ixodes ricinus. In man it produces an influenza-like illness with arthralgia, myalgia and headache. Small healthy wild rodents commonly become infected and apparently remain so for life. In the absence of infected ticks, exposure to wild rodents is unlikely to lead to human infections. Nevertheless, care should be taken to avoid contact of infected animal tissues and body fluids with cuts or abrasions on the skin.
Herpesvirus simiae or 10 Over 30 cases of infection with B virus, most of them fatal, due to B virus of monkeys exposure to monkeys or monkey tissues have been recorded with at least one instance of secondary transmission. Infection has occurred through monkey bites and through contact with monkey tissues in work in the laboratory. Serological screening should be done while the animal remains in quarantine before use. The risk of B virus transmission to workers can be almost eliminated by using primates shown to be B virus antibody negative.
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11 Considering the extreme potency of this infection, for which no reliably effective treatment is available, seropositive animals or those showing any sign of the infection (for example labial and oral vesiculation) should not be used.
SIV and STLV 12 Three cases have been recorded in laboratory workers of seroconversion to simian immunodeficiency virus (SIV). In one case, virus was recovered by isolation after a number of attempts but in none of the cases was there any detectable sign of disease. There is no record of human infection with simian T-cell lymphotropic virus (STLV).
13 While the pathogenic potential of SIV and STLV for humans remains uncertain, caution is advised. Their close relationship with the human counterparts HIV and HTLV strongly suggests the need for equivalent containment measures. SIV has recently been added to the Community classification of biological agents (and consequently also to the Approved List) in Hazard Group 3. Derogation applies as it does for some types of work with HIV! Auto-inoculation, for example, through an accident with a needle or other sharp probably presents the most important risk with simian retroviruses. (See Appendix 16.)
Prion diseases 14 So-called prion diseases are the transmissible spongiform encephalopathies (TSE) of man and animals. The animal prion diseases include scrapie in sheep and goats and BSE (bovine spongiform encephalopathy) occurring naturally in cattle. There is no record of occupational transmission of any of the TSE from either human or animal sources although all have been transmitted experimentally and across species boundaries. A small number of iatrogenic cases of Creutzdfeldt-Jakob disease (CJD) has been recorded (see Appendix 19).
15 As new guidance on TSE2 recommends, animals infected with the human agents should be handled with care. With scrapie, long experience suggests that the risk to humans is negligible or non-existent but with BSE, there is less certainty and again appropriate precautions are strongly recommended, directed principally at avoiding auto-inoculation of infected material especially neural tissues.
Rabies 16 Imported animals are subject to quarantine restrictions and as indicated Britain has been rabies-free for many years. (See Appendix 4.)
Ebola and 17 There have been several incidents in which imported monkeys have been Marburg viruses implicated in outbreaks of filovirus infections. In the case of Marburg, infection occurred in 31 laboratory workers with seven deaths. More recently, an Ebola-like virus was responsible for two lethal outbreaks in imported monkeys although none of the staff in the facility was apparently unwell despite exposure. In other outbreaks in humans, Ebola virus has been a
1 See Protection against blood-borne infections in the workplace; HIV and hepatitis 1995 ACDP, HMSO ISBN 0 11 321953 9 2 See Precautions for work with the human animal transmissable spongiform encephalopathies 1994...... ACDP, HMSO ISBN 0 11 321805 2. Page 100 Advisory Committee on Dangerous Pathogens ...... particularly virulent agent with a very high mortality rate. Extreme caution is therefore advised in handling imported simians.
18 New detailed guidance on the containment of experimental animals is in preparation. Guidance on handling simians previously issued by the Medical Research Council’ has been revised and will be reissued by the HSE as an ACDP publication.
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APPENDIX 15 GENETICALLY MODIFIED ORGANISMS AND BIOLOGICAL AGENTS
1 Work with biological agents which are at the same time genetically modified organisms (GMO) must comply with the COSHH Regulations 1994 and also with separate legislation relating specifically to genetic modification. This latter is the Genetically Modified Organisms (Contained Use) Regulations 1992 (‘the Contained use Regulations’) and the Genetically Modified Organisms (Deliberate Release) Regulations 1992 and 1995.
2 As a general rule, any duty performed to comply with the Contained Use Regulations will count as compliance with any overlapping requirement of COSHH. The main area of overlap concerns notification of HSE.
Risk assessment 3 COSHH and the GMO Regulations all require risk assessment. However, while COSHH assessments are based solely on the risk to human health, assessments under the GMO Regulations must take account of risks to both human health and the environment. Where an assessment has been made to meet the requirements of the GMO Regulations it does not need to be repeated for the same risks and activities as part of an assessment required by COSHH.
Classification 4 Under COSHH, biological agents are assigned to one of four Hazard Groups. Many agents appear on the Approved List (see Appendix 23) which specifies their hazard grouping indicating the appropriate level of containment. If a biological agent does not appear in the Approved List, it must be assigned to one of the four groups on the basis of the criteria set out in paragraph 3 of Schedule 9 in COSHH.
5 The Contained Use Regulations place responsibility on the person carrying out the work to classify genetically modified micro-organisms (GMM) into one of two groups based on criteria set out in a Schedule to the Regulations. At the time of writing, Group I includes GMM which are non- pathogenic to humans, animals or plants and non-harmful to the environment. The criteria are, however, expected to have changed by early 1996 when the concept of non-pathogenicity will be replaced by the test of whether an organism is unlikely to cause disease. All GMM not fulfilling the criteria for Group I are classified as Group II.
6 There is no direct relationship between the GMM classification and the COSHH Hazard Groups. Even though some of the wording will be similar once the new GMM classification criteria are in place, the interpretation is somewhat different. In particular, a Hazard Group 1 biological agent is defined as being ‘unlikely to cause human disease’ based on its level of risk of infection, although an agent in this group it will still present a hazard to human health possibly through being allergenic or because of toxin production. Under the revised GMM classification the key test will be ‘unlikely to cause disease’ but in this case disease is taken in its broadest sense and includes allergenicity and toxicity as well as infection hazards.
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7 These differences, together with the need for GMM classification to include consideration of risks to animals, plants and the environment, mean that it is difficult to generalise about how organisms classified under one scheme will be classified under the other. The following may help as illustrations:
a genetically modified biological agent classified in Hazard Group 2, 3 or 4 under COSHH will usually be a Group II GMM;
a genetically modified biological agent classified in Hazard Group 1 under COSHH, may be a Group II GMM, either because of allergenicity or toxicity to humans and/ or because of environmental risks;
a Group II GMM will not be a biological agent (as strictly defined) at all if there are no hazards to human health.
Control measures 8 Under COSHH, the selection of control measures for biological agents is prescribed strictly according to their risk to human health. However, the Contained Use Regulations set out containment measures which must be selected at a level appropriate to the assessment of risks to both human health and the environment. Where there is a mismatch, the more stringent control measures must be applied. This is particularly likely to arise for biological agents which are unlikely to cause disease in humans but are environmentally harmful.
Notification 9 The Contained Use Regulations require prior notification to HSE of the requirements first use of premises for genetic modification work and for subsequent individual activities with GMOs. For certain higher risk GMO, HSE must give consent before work can begin.
10 COSHH requires prior notification of the ‘first use’ of biological agents in Hazard Groups 2, 3 or 4 and subsequent notification of, for example, agents in Groups 3 and 4 when these have been provisionally classified by the employer. If the intention to use a genetically modified biological agent is notified under the Contained Use Regulations, a separate notification under COSHH for that agent will not be necessary.
11 Notification will however be required if the genetically modified biological agent appears in Part V of Schedule 9 in COSHH is being consigned to other premises or is to be imported (see paragraph 13 of Schedule 9 and Appendix 22). There is no notification requirement for transporting GMO under the Contained Use Regulations.
Further information More detailed advice on the statutory requirements affecting GMO is available from: Health and Safety Executive, Biotechnology Policy, Health Policy Division, Floor 7, South Wing, Rose Court, 2 Southwark Bridge London SE1 9HS (Tel: 0171 717 6249, Fax: 0171 717 6199).
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APPENDIX 16 BLOOD-BORNE VIRUSES
1 The term blood-borne virus (BBV) encompasses those viruses that persist in the blood, are known to be endemic in the population and are generally transmitted by contaminated blood or body fluids. They comprise three of the viruses that cause hepatitis and the viruses responsible for AIDS and human T-cell leukaemias. They are listed in the table below:
Abbreviation Full name Disease HIV 1 human immunodeficiency virus - Type 1 AIDS HIV 2 human immunodeficiency virus - Type 2 AIDS HBV hepatitis B virus hepatitis HCV hepatitis C virus hepatitis HDV hepatitis D virus (delta agent) hepatitis HTLV 1 human T- cell lymphotropic virus - Type 1 adult T-cell leukaemia TSP/HAM HTLV 2 human T-cell lymphotropic virus - Type 2 none known
Notes:
1 All these viruses are in Hazard Group 3.
2 Several different conditions may occur as a result of HIV infection and precede the development of AIDS but not all those with HIV have developed AIDS over a twelve year history of clinical observation.
3 Hepatitis C was not listed in the 1990 edition of the ACDP’s Categorisation of pathogens. It was subsumed there by the then current term ‘non-A non-B hepatitis’.
4 TSP = tropical spastic paraparesis; HAM = HTLV-associated myelopathy
2 The BBV are transmitted through entry of blood or contaminated body fluids into the body of a susceptible person. This may occur: in childbirth (either before or during the birth); in sexual intercourse; in blood transfusion; in sharing injecting equipment; or through skin puncture by blood contaminated objects such as needles, instruments or glass. In addition, infants of infected mothers may contract BBV infection through breast feeding. Less common means of transmission are through contamination of wounds and skin lesions (for example eczema), through splashing of the mucous membranes of the eye, nose or mouth, or through bites that draw blood. Blood transfusion in the United Kingdom carries only a remote risk of infection with BBV as all blood donations are screened for HBV, HCV and HIV. More detailed information and advice on the risk of transmission of BBV and the precautions that should be taken to avoid infection are given in a new guidance publication1.
1 See Protection against blood-borne infections in the workplace; HIV and hepatitis 1995 ACDP, HMSO ISBN 0 11 321953 9 ...... Page 104 Advisory Committee on Dangerous Pathogens ......
Hepatitis viruses 3 The most important causes of acute and chronic viral hepatitis are the five hepatotropic viruses termed hepatitis A, B, C, D and E. Hepatitis A and E are spread by the faecal-oral route, do not include a chronic carrier state and do not present a significant risk of blood-borne infection.
HEPATITIS B VlRUS (HBV)
4 HBV infection is endemic and common in developing countries where children acquire infection from mothers during birth or in early infancy. In Western Europe, North America and other developed countries, infection occurs sporadically by sexual contact and blood transfer, particularly by the sharing of needles and syringes in drug misuse and by inoculation injury in health care workers.
5 HBV is a DNA virus of the Hepadnavirus family. The infectious virion is a 40 nm spherical particle with a lipoprotein envelope comprised of hepatitis B surface antigen (HBsAg) which is detected in the major screening tests for HBV infection. An internal core protein (HBcAg) surrounds the viral DNA and a subunit of the HBcAg protein (HBeAg), is secreted into the plasma and is a useful marker of infectivity. In carriers of HBsAg the persistence of HBeAg indicates continuing potential infectivity for sexual partners, for babies born to carrier mothers, and for non-immune health care workers exposed by inoculation injury. The continued presence of HBeAg is also associated with progressive liver damage and risk of liver cancer. A vaccine for HBV produced by genetic modification gives good protection against infection. It is given in three doses and is recommended for all health care workers and for others in whom an occupational risk is recognised.
6 There are no totally reliable figures on the incidence of HBV infection/carriage in the population; approximately 1 in 1000-1500 new blood donors is found to be a carrier of HBsAg but this may not represent the nation as a whole.
HEPATlTlS D VIRUS (HDV)
7 HDV, previously known as the ‘delta agent’, is a defective virus or ‘virusoid’ that requires the presence and helper activity of HBV for its replication. Thus, hepatitis D occurs only in carriers of HBV or in people who acquire the two viruses simultaneously. Its mean incubation period is 35 days. HDV is prevalent in the Amazon basin, Equatorial Africa, the Middle East and Mediterranean basin, and in Asiatic areas of the former USSR. The HDV particle is 36 nm in diameter. Its single stranded RNA genome is circular and is enclosed by a nucleocapsid antigen, the HDV antigen, and encapsulated by HBsAg. Acute hepatitis D infection is usually severe. Double infection with HBV and HDV generally causes rapidly progressive disease and cirrhosis at an earlier age than with HBV infection alone.
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8 The existence of post-transfusion hepatitis caused by agents other than hepatitis A virus and HBV has long been recognised. Previously known as ‘non-A, non-B hepatitis’ (NANB), the main cause is now known to be HCV. Molecular cloning of the genes of HCV was reported in 1989 and as a result, the virus has been included in the Flavivirus family. The virus particle is 30-60 nm in diameter and has a lipid envelope. Although HCV cannot be grown in cell culture, antibody tests have been established and the RNA can be detected in serum and tissues by the polymerase chain reaction. Routine screening of blood donors has been introduced to prevent transmission. However, this infection is prevalent in injecting drug misusers and may be transmitted (but rarely) by sexual intercourse. Acute hepatitis C is often asymptomatic or mild but up to 50% of patients who develop acute HCV infection go on to suffer chronic hepatitis with the risk of cirrhosis and primary liver cancer. Early indications from routine testing of blood donations are that HCV infection is present in 1 in 5000 of blood donations.
Human 9 HIV-1 is responsible for the majority of HIV infections and cases of AIDS. immunodeficiency HIV-2 is found mainly in West Africa but infected individuals have been viruses (HIV) detected in other regions of Africa, Europe, India and the USA. The structure, genetic organisation, epidemiology and clinical effects of the two viruses are very similar and their properties are presented under the term ‘HIV’. HIV belongs to the Retrovirus family in the genus Lentivirinae. It contains two identical strands of RNA and the name retrovirus comes from the abilitity of these viruses to reverse transcribe their RNA into a DNA copy by means of an enzyme ( reverse transcriptase) which is present in the virus particles.
1O HIV has a lipid envelope derived from the host cell into which the viral glycoproteins, gp120 and gp41, are inserted. The envelope is susceptible to damage by heat, disinfectants and detergents which forms the basis of decontamination procedures, but it also protects the virus from dehydration so that infectivity can persist, even on drying, in ambient conditions. HIV infects cells by fusion of gp120 with the CD4 antigen, which is expressed on helper T lymphocytes, mononuclear phagocytes and some neural cells. After uncoating, reverse transcription of the viral RNA forms a DNA copy which is then integrated into the host cell DNA. The integrated viral DNA is in a latent, or relatively inactive state early in the course of HIV infection and is then activated by several factors leading to the production of progeny viruses which bud from the cell membrane. Cells are not killed rapidly and there is persistent productive infection of helper T lymphocytes, macrophages and other mononuclear phagocytes and also of cells in the central nervous system. With time, cell damage occurs and the circulating population of helper T cells falls and, in some individuals, progressive encephalopathy develops
11 All available evidence indicates that blood, semen and female genital tract secretions are by far the most important vehicles of infection with HIV.
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Infection of babies from infected mothers has been attributed to transplacental infection, exposure during delivery and to breast feeding. It is estimated that up to 50 000 individuals in the UK may be infected with HIV (approximately 1 in 1000 of the population) but definitive evidence from screening major population groups is not available. Some geographic areas and particular population groups have a much higher incidence. Most infected individuals develop antibody to HIV within three months of infection. Infectious virus is present in blood and body fluids at all stages of infection but there are indications that infectivity is higher at the time of seroconversion and in the later stages of disease when the number of CD4 positive cells is very low.
Human T-cell 12 HTLV-1 is associated with certain types of leukaemia/lymphoma and also lymphotropic viruses - chronic neurological disease known as tropical spastic paraparesis (TSP) or HTLV 1 and HTLV 2. HTLV-1 associated myelopathy (HAM). HTLV-1 is particularly prevalent in Japan and the Caribbean area but there is evidence of infection in all communities. A related virus, HTLV-2, was originally isolated from an atypical case of hairy cell leukaemia but no specific disease has been attributed to it. The incidence of infection with these retroviruses in the population of the UK is not known but would appear to be very low. There is no record of HTLV infection resulting from occupational exposure to blood or to these viruses when used in research.
Simian retroviruses - 13 The new guidance on HIV and hepatitis (see footnote on page 104) SIV and STLV makes reference to retroviruses found in animals. On present evidence, those of concern are simian immunodeficiency virus (SIV) and simian T-cell lymphotropic virus (STLV). SIV has caused infection but no observable disease in laboratory workers and as a consequence has been added to the EC classification of biological agents. It has been placed in Hazard Group 3 but with the facility for derogation (see certificate of exemption accompanying the Approved List of biological agents).
14 SIV infected animals must be held at Animal Containment Level 3 and while there is uncertainty about its ability to infect humans, it is recommended that STLV-infected animals are treated similarly. In the laboratory, propagation or concentration of SIV and STLV must be carried out at Containment Level 3 as for HIV and HTLV. Other operations (for example serology) with SIV or STLV-infected material may be conducted under Containment Level 2 conditions but with the extra precautions recommended in the new guidance for similar work with HIV. These are essentially aimed at minimising the risk of self-inoculation by, for example the avoidance of sharps and strict attention to surface decontamination.
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APPENDIX 17 MYCOBACTERIA
1 The familiar mycobacterial species listed in Hazard Group 3 in the categorisation are those capable of causing serious disease which requires a prolonged course of treatment. The further inclusion of opportunistic mycobacteria, which are ubiquitous in the environment, might appear to be unnecessary but when handling pure cultures of these agents, Containment Level 3 procedures should be adopted. This is because some can cause pulmonary disease which is contracted by the inhalation of infectious airborne particles. While this usually occurs in subjects who have pre-existing lung conditions or who are immunocompromised, cases have been seen in people who fall into neither of these categories. Laboratory staff therefore need to be protected.
2 In many subjects, pulmonary disease caused by opportunistic mycobacteria responds to treatment with conventional anti-tuberculosis chemotherapy despite the resistance in vitro of the organisms concerned. However, treatment has to be continued for up to two years and, as approximately 30% of patients do not respond, surgery may have to be considered.
3 This view resulted in the transfer of M. avium and M. scrofulaceum from Hazard Group 2 to Group 3. These two species are so closely related to M. intracellulare that it does not make sense to leave them in the lower hazard group. From a clinical point of view, it is sufficient to identify a strain as belonging to the M. avium-intracellulare-scrofulaceum complex (MAIS) as the prognosis and treatment are the same whichever member of the complex is concerned. In the 1990 edition of the categorisation, the inclusion of M. paratuberculosis in Hazard Group 3 was a precautionary measure. Since then, an extensive review of the literature has been conducted and it is now considered appropriate to adhere to the lower hazard grouping given this agent in the European Directive on the classification of biological agents. At this stage, there appears to be no conclusive evidence that this organism is responsible for Crohn’s disease.
4 The mycobacteria placed in Hazard Group 2 in 1990 categorisation are those that cause localised non-pulmonary infections. While infection with these agents may be superficial, such as tropical fish-tank granuloma (M. marinum) or Buruli (Bairnsdale) ulcer (M. ulcerans) there can be serious consequences. M.ulcerans has been now been placed in Group 3 by the EC Directive (but see paragraph 6). Neither of these species causes pulmonary disease while M. chelonei and M. fortuitum are primarily involved in local abscesses and only rarely infect the lung.
5 Other mycobacteria such as M. gordonae and M. terrae can be isolated from clinical specimens but they are usually present only as casual non- pathogenic contaminants and as such do not require categorisation above Hazard Group 1.
...... Page 108 Advisory Committee on Dangerous Pathogens 6 The BCG strains of M. bovis and the so-called ‘vole bacillus’ M. microti have both been used in vaccines but, if mishandled, can give rise to abscess formation. The BCG strains are included in Hazard Group 2 because of this and the extremely remote possibility of reversion to virulence although when used under clinic conditions for immunisation, laboratory Containment Level 2 is not necessary. As with M.ulcerans, the EC Directive has placed M.microti in the higher Hazard Group 3 but in both cases there is the facility for derogation (see certificate of exemption accompanying the Approved List of biological agents). In practice, this means that the ACDP recommendation is that a specific assessment should be made of the activity to be undertaken - the volume of material to be cultured, the necessity of using sharps, the procedures and equipment to be used in, for example, disrupting cells. This may lead to adoption of full Containment Level 3 despite the derogation.
7 The steady decline in the notification rate of tuberculosis ceased in the late 1980s and since then there has been a small rise. For example, the figure for 1992 for England and Wales was 5% higher than in 1991 and this upward trend has been maintained. The increase is largely confined to four health regions namely North East and South East Thames, Yorkshire and West Midlands.
8 The precise reasons for this are not clear. However, it does not appear to be related to tuberculosis developing in patients with AIDS and the overlap between the HIV infected population and those previously infected with tuberculosis in whom the capability of reactivation is limited. This is not the case in other parts of the world particularly in the inner city areas of the USA and in sub-Saharan Africa.
9 Another disturbing development has been the emergence of multi-drug resistant strains of Mycobacterium tuberculosis which have been implicated in outbreaks of infection in hospitals and prisons affecting both inmates and care workers. These reports have originated largely in the USA and have again been linked with HIV infection. There is no evidence of this occurring to a large extent in England and Wales but the situation is being closely monitored.
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1 Poxviruses (the family Poxviridae) are the largest and most complex viruses. They contain double-stranded DNA, replicate in the cytoplasm of infected cells, and contain a variety of enzymes essential for replication. Because of this dependence on virion-associated enzymes, purified poxvirus DNA is not infectious.
2 Poxviruses which infect humans are distributed among four genera.
Orthopoxvirus: Smallpox, monkeypox, cowpox, buffalopox, vaccinia. Parapoxvirus: Orf (contagious pustular dermatitis), milker’s nodes (pseudocowpox). Yatapoxvirus: Tanapox, Yabapox. Molluscipoxvirus: Molluscum contagiosum.
3 Historically, much attention was always focused on smallpox and smallpox vaccine (vaccinia) virus. Because of the ease with which vaccinia virus can be grown it was often used as a ‘representative’ DNA virus not only in research laboratories but also in undergraduate experiments. Now that smallpox has been eradicated the remaining poxviruses, with the possible exception of monkeypox virus, are relatively unimportant as human pathogens. However, more widespread work on vaccinia and parapoxviruses is being done by those interested in their use as recombinant vectors.
4 With the exception of vaccinia which has no natural reservoir and Molluscum contagiosum, all other poxviruses which infect humans have animal reservoirs. Thus, with the exception of molluscum, all naturally- acquired poxvirus infections are zoonoses.
5 In some cases the reservoir hosts are known, for example orf (sheep), milker’s nodes (cattle). With others, the animal reservoirs are not known with certainty, but probably include squirrels (monkeypox) and rodents (cowpox). Cats have been implicated in the transmission of cowpox to humans but this may result from their contact with infected rodents.
6 Human infection may occur with any of viruses listed and a rational approach to risk assessment will take account of: (a) the appropriate containment level for the different viruses; (b) the source and purpose of use of the viruses, in particular whether they are known viruses, diagnostic specimens, or potentially infected material; (c) the animal source and country of origin; (d) any particular precautions that may be necessary, including vaccination.
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Laboratory containment SMALLPOX
7 Smallpox (variola) virus is included in the categorisation of biological agents in Hazard Group 4 although the only remaining virus stocks are held in high security facilities in the USA and Russia. By international agreement, no work on smallpox virus is conducted in any other countries.
MONKEYPOX
8 Monkeypox (Hazard Group 3) is a zoonosis of West and Central Africa with a relatively high mortality (16%) in the unvaccinated and some capacity for person-to-person spread via respiratory aerosol. It is unlikely to be encountered outside research laboratories. It should noted that work with monkeypox virus now requires prior notification to HSE via the new notification arrangements in COSHH 1994. The virus is listed in Part V of Schedule 9 of the Regulations.
9 The remaining poxviruses are appropriately placed in Hazard Group 2 because they are infectious only by inoculation, and produce relatively mild infections with no capacity for case-to-case spread if adequate precautions are taken by the infected individual and contacts.
Sources of poxviruses 10 Those working with known strains of poxviruses should be fully aware of the precise risks involved. This will include those handling recombinant vaccinia and parapoxviruses where the human pathogenicity may be attenuated, unaltered or enhanced.
11 Infection is also an occupational hazard of those working in diagnostic laboratories, veterinary surgeries, abattoirs etc. Here knowledge that, for example domestic cats are the most commonly recognised host of cowpox, which has also infected captive exotic species (for example cheetahs, elephants) and their handlers will prove useful. Geographical distribution of the viruses is also a relevant factor, with only cowpox, parapox and molluscum viruses indigenous to the United Kingdom. Although a precise identification of any infecting virus may not necessarily affect the prognosis, it may assist investigations into the source and prevention of future infections.
Precautions 12 Special precautions beyond those normally required for handling Hazard Group 2 pathogens are not necessary for most work with poxviruses in Group 2. However, individual workers may prefer to use eye protection and/or gloves; the former when high concentrations are being used, the latter if cuts or scratches are present on the hand. When considering the risks to health of workers, the enhanced severity of infection in the eczematous or those being treated, for example, with corticosteroids should be considered and appropriate counselling given.
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Vaccination 13 Although smallpox vaccination is most strongly recommended for those working with monkeypox virus (some employers may choose to make it a condition), present recommendations from the ACDP and the ACGM are that vaccination should not be given to those doing routine work with Hazard Group 2 orthopoxviruses1. However, case-by-case assessment is required for those involved in large-scale work or animal inoculation, where recombinants may have enhanced virulence, and where individuals would prefer vaccination.
14 The relationship between the safety of vaccination and the protection it offers on the one hand, with the risk and effects of accidental infection on the other is delicately balanced and some countries, for example, the USA, require vaccination in circumstances where United Kingdom recommendations do not.
1 See Vaccination of laboratory workers handling vaccinia and related poxviruses for humans 1990 ACDP and ACGM HMSO ISBN 0 11 885450 X...... Page 112 Advisory Committee on Dangerous Pathogens ......
APPENDIX 19 TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
1 Transmissible spongiform encephalopathies (TSE) or ‘slow virus’ encephalopathies or ‘prion disease’, include the conditions seen in humans, Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS) and kuru. In animals, scrapie occurs in sheep and goats and there are other transmissible encephalopathies of mink, deer and elk. In 1986, a new form of TSE, bovine spongiform encephalopathy (BSE) appeared in cattle; it shares some of the characteristics of scrapie.
2 The diseases that affect humans are very rare (0.5 to 1 cases of CJD per million of the population per year) and while they and the similar conditions that affect animals are clearly transmissible under certain special conditions, no causal agent has yet been identified. Also, the agents responsible are unconventional in that they provoke no detectable immune response in the affected host.
3 One of the properties of the TSE agents, which is of great practical importance in both clinical and laboratory work, is an apparently remarkable resistance to heat, radiation and chemical inactivation. Early experimental work with scrapie, later confirmed with CJD, led to the recommendation of sterilisation and disinfection procedures far more stringent than those usually applied in hospital practice for the control of conventional infections. A DHSS Report of 19811 and a later letter from the Department to administrators (DA(84)16) specified autoclaving contaminated re-usable items such as surgical instruments at temperatures of 134°C to 138°C for not less than 18 minutes (hold time at temperature) or for six separate cycles of 3 minutes. The downward displacement autoclave (which is the type most commonly used in laboratories), may be less effective even at these high temperatures than is the surgical steriliser operating with a pulsed vacuum cycle.
4 Scrapie-infected tissue stored in 10% formalin has been shown to be still capable of transmitting infection to experimental animals after some years which illustrates the resistance of this agent to a normally highly effective biocidal treatment. The other TSE agents appear to be similarly resistant although some strain variation is apparent between and within them. Other potent chemicals long used for decontamination in a variety of settings also appear to be ineffective (for example 10% phenolic disinfectant, glutaraldehyde, B-propiolactone). However, the application for extended periods of a solution of sodium hypochlorite containing 20 000 ppm available chlorine appears to reduce infectivity substantially if not eliminating it altogether. Advice should be obtained from specialist sources before any choice is made of alternative disinfectants for decontamination of CJD etc which must be presumed to have the same level of resistance as that demonstrated with scrapie. There is a particular practical difficulty in, for example, disinfecting safety cabinets because of resistance to the action of formaldehyde and other fumigants that might be used. Consequently, special arrangements need to be made in order that filter-changing and maintenance 1 See Report of the Advisory Group on the management of patients with spongiform encephalopathy (Creutzfeldt-Jakob Disease) to the chief Medical Officers DHSS 1981 HMSO...... ISBN 0 11 320778 6. Page 113 Advisory Committee on Dangerous Pathogens ...... work may be carried out safely, for example by selecting a cabinet designed to allow safe bagging of filters in the process of removal.
5 Iatrogenic transmission of CJD has occurred through the use of neurosurgical instruments, corneal transplantation, prosthetic surgery on the ear drum (ie using donor dura mater) and the administration of human growth hormone prepared from the pituitary glands of cadavers. However, these events have been relatively rare and none has occurred since the risk was recognised and control measures introduced. Growth hormone, for example, is now obtained through the use of biotechnology and not from donor tissue.
6 While CJD and the other TSE are transmissible, it is important to stress that they are not contagious. No proven case of occupationally-acquired TSE has been recorded. CJD and GSS are, in any case, rare diseases and kuru is confined to a discrete area of New Guinea where it is in decline. However, the long incubation period of this group of infections makes cause and effect somewhat difficult to relate. Two cases of CJD in ex-laboratory workers, who had both handled neural tissues extensively during their working lives, are a matter of concern but association with work remains purely speculative.
7 Nevertheless, particular caution is advised in dealing with tissue from the central nervous system, especially when it comes from known or suspected cases of the human diseases CJD, GSS and kuru. New detailed guidance on the TSEs has been published’ recommending suitable laboratory containment procedures and decontamination methods as well as providing background information on the subject.
8 The human TSE agents, CJD,GSS and kuru, were placed by the EC Directive on the classification of biological agents in Hazard Group 3. However, as there is no evidence that these agents are transmissible by the airborne route, derogation from full Containment Level 3 is normally permitted. The agents of CJD, GSS and kuru are therefore specified in the exemption certificate accompanying the Approved List. On condition that employers follow the guidance referred to in paragraph 7 above, certain containment measures normally used for work with Hazard Group 3 agents may be dispensed with.
9 In view of the extreme durability of the TSE agents and the remote likelihood that if occupational transmission were to occur, it would be by the percutaneous route , concentration should be focused on ensuring that equipment and working surfaces are subjected to the recommended stringent decontamination procedures. For these and other reasons, work practices should be reviewed so as to eliminate or minimise the use of sharps, to avoid puncture wounds and cuts and contamination of the skin or mucous membranes with TSE tissues and body fluids. Eye protection and gloves should be worn when there is any risk of splashing.
1 See Precautions for work with the human animal transmissible spongiform encephalopathies ACDP 1994 HMSO ISBN 0 11 321805 2.
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10 Following detailed consideration by the Southwood Committee1 and other groups since then, it is clear that there is insufficient evidence on which to consider the allocation of the agent responsible for BSE to an ACDP hazard group. However, while uncertainty remains about the potential for its transmission to humans, it is prudent to treat known or suspected BSE- affected tissues with caution. The new guidance addresses this issue and also provides recommendations applicable to work with other animal TSE.
1 See Report of the Working Party on Bovine Spongiform Encephalopathy Department of Health and Ministry of Agriculture Fisheries and Food 1989 ISBN 1 85197 405 9.
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APPENDIX 20 PATHOGENS CONTROLLED BY THE AGRICULTURE AND FISHERIES DEPARTMENTS
Pathogens of animals 1The Importation of Animals Pathogens Order 1980 prohibits the and poultry importation into Great Britain from outside the European Community of any pathogen that may cause disease in agricultural animals or birds, or any material in which a pathogen might be carried, except under the authority of a licence in writing issued by the appropriate Minister and in accordance with the conditions of that licence. The ‘appropriate Minister’ in the application of this Order in England means the Minister of Agriculture, Fisheries and Food; in Scotland, the Secretary of State for Scotland; and in Wales, the Secretary of State for Wales.
2 The Specified Animal Pathogens Order 1993 prohibits any person in Great Britain from holding or introducing into animals a specified animal pathogen or carrier containing that pathogen except under the authority of a licence issued in writing by the appropriate Minister. The specified animal pathogens are those organisms causing serious epidemic diseses of farm livestock. They are:
BACTERIA, MYCOPLASMS AND RlCKETTSlAS Burkholdaria (Pseudomonas) mallei Bacillus anthracis Brucella melitensis Brucella suis Brucella ovis Mycoplasma agalactia Mycoplasma mycoides Mycoplasma mycoides var capri
FUNGI Histoplasma farciminosum
VIRUSES
HERPESVIRIDAE Aujeszkys disease
IRIDOVIRIDAE African swine fever
ORTHOMYXOVIRIDAE Avian influenza (Fowl plague)
PARAMYXOVIRIDAE Morbilliviruses Rinderpest Peste des petits ruminants Paramyxoviruses Newcastle disease ...... Page 116 Advisory Committee on Dangerous Pathogens ......
PICORNAVIRIDAE Enteroviruses Swine vesicular disease Teschen disease Rhinoviruses Foot and mouth disease
POXVIRIDAE Sheep pox, goat pox and horse pox Lumpy skin disease
REOVIRIDAE Orbiviruses African horse sickness Bluetongue
RETROVIRIDAE Unclassified Equine infectious anaemia
RHABDOVIRIDAE Rabies and rabies-related viruses Vesicular stomatitis
TOGAVIRIDAE Alphaviruses Equine encepholomyelitis (eastern, western and Venezuelan)
ARTERIVIRUSES Pestiviruses Swine fever (hog cholera)
BUNYAVIRUSES Rift valley fever
CALICIVIRUS Viral haemorrhagic disease of rabbits
PARASITES Babesia caballi Babesia equi (equine piroplasmosis) Cochliomyia hominivorax (Screw worm) Echinococcus granulosus and multilocularis Theileria annulata (Theileriasis) Trichinella spiralis Trypanosoma equiperdum Trypanosoma evansi Trypanosoma theileri
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3 Details of the requirements for the importation or handling of pathogens of animals or poultry may be obtained from:
Ministry of Agriculture, Fisheries and Food Animal Health (Zoonoses) Division Hook Rise South Tolworth, KT6 7NF (Tel: 0181 330 4411) (Fax: 0181 330 8419)
Scottish Office Agriculture and Fisheries Department Pentland House 47 Robbs Loan Edinburgh, EH14 1TW (Tel: 0131 556 8400) (Fax: 0131 244 6475)
Welsh Office Agriculture Department Crown Buildings Cathays Park Cardiff, CF1 3NQ (Tel: 01222 693131)
Pathogens of 4 The following virus of rabbits is controlled by an Order made under the other animals Pests Act 1954:
POXVlRlDAE Leporipoxviruses Myxoma
5 Details of the requirements may be obtained from:
Ministry of Agriculture, Fisheries and Food Worpledon Laboratory Tangley Place Worplesdon, GU8 3LQ (Tel: 01483 232581)
6 The following virus of rabbits is controlled by Orders made under the Animal Health Act 1981:
CALICIVIRIDAE Viral haemorrhagic disease (Rabbit haemorrhagic disease)
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7 Details of requirements may be obtained from:
Ministry of Agriculture, Fisheries and Food Animal Health (Disease Control) Division Branch A Hook Rise South Tolworth Surbiton Surrey KT6 7NF
Pathogens of bees 8 The Bees Act 1980 makes provision for the control of pests and diseases affecting honey bees, and there are two Orders made under the Act. The Importation of Bees Order 1980 and its 1987 Amendment make provision for the statutory control of honey bee imports including their pathogens. The Bee Diseases Control Order 1982 makes the following diseases of bees notifiable.
BACTERIA Bacillus larvae (American foul brood) Melissococcus pluton (European foul brood)
PARASlTES Varroa jacobsoni (varroasis)
9 Details concerning legislation and statutory procedures may be obtained from:
Ministry of Agriculture, Fisheries and Food Horticulture Branch A Ergon House 17 Smith Square London, SW1 P 3HX (Tel: 0171 238 3000)
Pathogens of fish 10 The following pathogens of fish cause diseases that are notifiable and controlled by Orders under the Diseases of Fish Acts 1937 and 1983, or under the Fish Health Regulations 1992 and 1993. The importations of fish and shellfish are controlled under this legislation to ensure consignments are free of the notifiable and listed diseases and any other serious diseases exotic to GB.
BACTERIA Aeromonas salmonicida Renibacterium salmoninarum Yersinia ruckerii
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PARASITES Gyrodactylus salaris Myxosoma cerebralis Bonamia ostreae Marteilia refringens
V/RUSES Birnaviridae Infectious pancreatic necrosis
Rhabdoviridae Infectious haematopoietic necrosis Spring viraemia of carp Viral haemorhagic septicaemia
UNCLASSIFIED Infectious salmon anaemia
11 Details of the requirements may be obtained from:
Ministry of Agriculture, Fisheries and Food Fish Disease Laboratory The Nothe Weymouth, DT4 8UB (Tel: 013057 72137)
Pathogens of plants The Plant Health (Great Britain) Order 1993 prohibits the importation from non-EC countries of any plant pathogen or plant pest which is not already established in Great Britain. The Order also controls the spread of quarantine plant pathogens and pests within Great Britain. The controlled pathogens and pests may only be imported into Great Britain for experimental purposes under a licence issued by the appropriate Minister. The Order also controls any activity which involves genetically modified plant pests.
In addition to plant pathogens and pests of agricultural and horticultural crops The Plant Health (Great Britain) Order 1993 also controls certain tree pathogens and pests.
The following pathogens and pests of plants are specifically controlled by The Plant Health (Great Britain) Order 1993.
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INSECTS, MITES AND NEMATODES, AT ALL STAGES OF THEIR DEVELOPMENT
Acleris spp.(non-European) Budworm and Fireworm Moths Aculops fuchsiae Fuchsia Gall Mite Aleurocanthus spp. Whiteflies Amauromyza maculosa Lettuce Leaf Miner Fly Anomala orientalis Oriental Beetle Anoplophora chinensis Citrus Longhorn Beetle Anoplophora malasiaca White-Spotted Longicorn Beetle Anthonomus bisignifer Strawberry Weevil Anthonomus grandis Cotton Boll Weevil Anthonomus signatus Strawberry Blossom Weevil Aonidiella citrina Yellow Scale Aphelenchoides besseyi White Tip Nematode Arrhenodes minutus Oak Timberworm Beetle Aschistonyx eppoi Japanese Gall Midge Bemisia tabaci Tobacco Whitefly Bursaphelenchus xylophilus Pine Wood Nematode Carposina niponensis Peach Fruit Moth Cephalcia lariciphila A Web-Spinning Sawfly
Cicadellidae (non-European) known to be vectors of Pierce’s disease (caused by Xylella fastidiosa), such as:
(a) Carneocephala fulgida A Leafhopper (b) Draeculacephala minerva Green Sharpshooter Leafhopper (c) Graphocephala atropunctata A Leafhopper
Choristoneura spp. (non-European) Budworm Moths Circulifer haematoceps Mediterranean Leafhopper Circulifer tenellus Beet Leafhopper Conotrachelus nenuphar Plum Curculio Weevil Daktulosphaira vitifoliae Grape Phylloxera Dendroctonus micans European Spruce Beetle Diaphorina citri Citrus Psylla Ditylenchus destructor Potato Tuber Nematode
Ditylenchus dipsaci Stem and Bulb Nematode Enarmonia packardi Cherry Fruit Worm Moth Enarmonia prunivora Lesser Appleworm Moth Eotetranychus lewisi Lewis’ Spider Mite Eotetranychus orientalis A Spider Mite Gilpinia hercyniae European Spruce Sawfly Globodera pallida White Potato Cyst Nematode Globodera rostochiensis Yellow Potato Cyst Nematode Gonipterus scutellatus Eucalyptus Snout Beetle Grapholita inopinata A Totricid Moth
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Heliothis armigera Old World Bollworm Heliothis zea Corn Earworm Moth Hishimonus phycitis A Leaf hopper Ips amitinus Smaller Spruce Bark Beetle Ips cembrae A Bark Beetle Ips duplicatus A Bark Beetle Ips sexdentatus A Bark Beetle Ips typographus Spruce Bark Beetle Leptinotarsa decemlineata Colorado Beetle Leucaspis japonica An Armoured Scale Liriomyza bryoniae Tomato Leaf Miner Liriomyza trifolii American Serpentine Leaf Miner Liriomyza huidobrensis South American Leaf Miner Liriomyza sativae Vegetable Leaf Miner Listronotus bonariensis Argentine Stem Weevil Longidorus diadecturus A Nematode
Margarodes, non-European species Scale Insects such as:
(a) Margarodes vitis (b) Margarodes vredendalensis (c) Margarodes prieskaensis
Matsucoccus feytaudi A Scale Insect Monochamus spp. (non-European) Sawyer Beetles Myndus crudus A Cixiid Bug Nacobbus aberrans False Root Knot Nematode Numonia pyrivorella Pear Fruit Moth Oligonychus perditus A Mite Opogona sacchari Sugar Cane Moth Pissodes spp. (European) Pine Weevils Popillia japonica Japanese Beetle Premnotrypes spp. (non-European) Potato Weevils Pseudopityophthorus minutissimus A Bark Beetle Pseudopityophthorus pruinosus A Bark Beetle Radopholus citrophlius Citrus burrowing Nematode Radopholus similis Banana Root Nematode Saissetia nigra Black Scale; Satsuma dwarf virus Scaphoideus luteolus Whitebanded Elm Leafhopper Scirtothrips aurantii South African Citrus Thrips Scirtothrips dorsalis Chilli Thrips Scirtothrips citri Citrus Thrips Scolytidae spp. (non-European) Bark Beetles Spodoptera eridania Southern Armyworm Moth Spodoptera frugiperda Fall Armyworm Moth Spodoptera litura Asian Cotton Leafworm Moth Spodoptera littoralis African Cotton Leafworm Moth
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Sternochetus mangiferae Mango Weevil Tachypterellus quadrigibbus Apple Curculio Weevil Tephritidae (non-European) Fruit Flies such as:
(a) Anastrepha fraterculus South American Fruit Fly (b) Anastrepha ludens Mexican Fruit Fly (c) Anastrepha obliqua West Indian Fruit Fly (d) Anastrepha suspensa Caribbean Fruit Fly (e) Dacus ciliatus Lesser Melon Fly (f) Dacus cucurbitae Melon Fly (g) Dacus dorsalis Oriental Fruit Fly (h) Dacus tryoni Queensland Fruit Fly (i) Dacus tsuneonis Japanese Orange Fruit Fly (j) Dacus zonatus Peach Fruit Fly (k) Epochra canadensis Currant Fruit Fly (l) Pardalaspis cyanescens Tomato Fruit Fly (m) Pardalaspis quinaria Rhodesian Fruit Fly (n) Pterandrus rosa Natal Fruit Fly (o) Rhacochlaena japonica Japanese Cherry Fruit Fly (p) Rhagoletis cingulata Eastern Cherry Fruit Fly (q) Rhagoletiscompleta Walnut Husk Fly (r) Rhagoletisfausta Black Cherry Fruit Fly (s) Rhagoletis indifferens Western Cherry Fruit Fly (t) Rhagoletis mendax Blueberry Maggot Fly (u) Rhagoletis pomonella Apple Fruit Fly (v) Rhagoletis ribicola Dark Currant Fly (w) Rhagoletis suavis Walnut Husk Fly
Thaumetopoea pityocampa Pine Processing Moth Thrips palmi Palm Thrips Toxoptera citricidus Brown Citrus Aphid Trioza erytreae Citrus Psyllid Bug Unaspis citri Citrus Snow Scale Xiphinema americanum American Dagger Nematode (non-European populations) Xiphinema californicum A Dagger Nematode
BACTERIA
Citrus greening bacterium Citrus variegated chlorosis Clavibacter michiganensis ssp. insidiosus Lucerne Bacterial Wilt Clavibacter michiganensis ssp. Tomato Bacterial canker michiganensis Clavibacter michiganensis ssp. sepedonicus Potato Bacterial Ring Rot Curtobacterium flaccumfaciens pv. Bean Bacterial wilt flaccumfaciens Erwinia amylovora Fireblight
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Erwiniastewartii Stewart’s Maize Bacterial Wilt Erwinia chrysanthemi pv. dianthicola Carnation Slow Wilt Pseudomonas solanacearum Potato Brown Rot Pseudomonas syringae pv. persicae Peach Bacterial dieback Spirioplasma citri Citrus Little Leaf and Stubborn Disease Xanthomonas campestris (all strains Citrus canker pathogenic to Citrus) Xanthomonas campestris pv. oryzae and Rice Leaf Blight; Rice Leaf Streak pv. oryzicola Xanthomonas campestris pv. phaseoli Bean Common Blight Xanthomonas campestris pv. pruni Cherry Leaf spot and Shothole Xanthomonas campestris pv. vesicatoria Tomato Bacterial Scab/Spot Xanthomonas fragariae Strawberry Angular Leaf Spot Xylophilus ampelinus Vine Bacterial Blight Xylella fastidiosa Pierce’s Disease of Grape
FUNGI
Alternaria alternata (non European) Apple and Pear Leaf Spot Apiosporina morbosa Cherry Black Knot Atropellis spp Pine Cankers Ceratocystis coerulescens Maple Sap Streak Ceratocystisfagacearum Oak Wilt Ceratocystisfimbriata Canker Stain of Plane Cercoseptoria pini-densiflorae Pine Needle Blight Cercospora angolensis Cercospora Citrus Fruit Spot Ciborinia camelliae Camellia flower blight Chrysomyxa arctostaphyli Broom rust Colletotrichum acutatum Strawberry Black Spot Cronartium spp. (non-European) Blister Rusts of Pine Cryphonectria parasitica Chestnut Blight Diaporthe vaccinii Blueberry Stem and Root Blight Didymella ligulicola Chrysanthemum rayblight Elsinoe spp. Citrus Scab Endocronartium spp. (non-European) Western Gall Rust Fusarium oxysporum f.sp albedinis Palm Bayoud Disease Glomerella gossypii Cotton Boll Rot Gremmeniella abietina Scleroderris Conifer Canker Guignardia citricarpa Citrus Black spot Guignardia laricina Larch Shoot Blight Guignardia piricola Pear Ring Spot Gymnosporangium spp. (non-European) Fruit - Juniper Rusts Hypoxylon mammatum Poplar Canker lnonotus weirii Conifer Butt rot Melampsora farlowii Hemlock Rust Melampsora medusae Poplar Rust Monilinia fructicola Fruit brown rot
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Mycosphaerella larici-leptolepsis Larch Needle Cast Mycosphaerella populorum Septoria Canker of Poplar Phialophora cinerescens Carnation Wilt Phoma andina Potato Black Blight/Leaf Spot Phoma tracheiphila Mal secco, Citrus Wilt Phyllostictasolitaria Apple Blotch Phytophthora cinnamomi Avocado Root Rot Phytophthora fragariae Strawberry Red core Plasmopara halstedii Sunflower Downy mildew Puccinia horiana Chrysanthemum White Rust Puccinia pittieriana Common Potato Rust Scirrhia acicola Pine Brown Spot Needle Blight Scirrhia pini Pine Red Band Needle Blight Septoria lycopersici Tomoto Annular Leaf Spot Synchytrium endobioticum Potato Wart Disease Thecaphora solani Potato Smut Trechispora brinkmannii Texas Root Rot Venturia nashicola Japanese and Chinese Pear scab Verticillium albo-atrum Verticillium Wilt of Hops Verticillium dahliae Verticillium Wilt of Hops
VIRUSES AND VIRUS-LIKE ORGANISMS
Andean potato latent virus Andean potato mottle virus Arracacha virus B, oca strain Apple proliferation mycoplasm Apricot chlorotic leafroll mycoplasm Arabis mosaic virus Bean golden mosaic virus Beet curly top virus (non-European isolates) Beet leaf curl virus Beet necrotic yellow vein virus (Beet Rhizomania) Black raspberry latent virus Blight and Blight-like organisms of citrus Blueberry leaf mottle virus Cadang-Cadang viroid Cherry leaf roll virus (in Rubus) Cherry rasp leaf virus (American) Chrysanthemum stunt viroid Citrus mosaic virus Citrus tristeza virus Citrus vein enation woody gall organism Cowpea mild mottle virus Elm phloem necrosis mycoplasm Euphorbia mosaic virus Florida tomato virus Grapevine Flavescence dorée MLO
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Leprosis (of Citrus) Lettuce infectious yellows virus Little cherry pathogen (non-European isolates) Naturally spreading psorosis (of Citrus) Palm lethal yellowing mycoplasm Pear decline mycoplasm Pepper mild tigré virus Peach mosaic virus (American) Peach phony rickettsia Peach rosette mosaic virus Peach rosette mycoplasm Peach X-disease mycoplasm Peach yellows mycoplasm Plum line pattern virus (American) Plum pox virus Potato Stolbur mycoplasm Potato black ringspot virus Potato spindle tuber viroid Potato virus T Potato viruses non-European isolates of A, M, S, V, X and Y (including Y0, Y n and Y c) and Potato leaf roll virus Prunus necrotic ringspot virus (in Rubus) Raspberry leaf curl virus (American) Raspberry ringspot virus Satsuma dwarf virus Squash leaf curl virus Strawberry crinkle virus Strawberry latent ‘C’ virus Strawberry latent ringspot virus Strawberry mild yellow edge virus Strawberry vein banding virus Strawberry witches’ broom mycoplasm Tatter leaf virus (of Citrus) Tobacco ringspot virus Tomato black ring virus Tomato ringspot virus Tomato spotted wilt virus Witches broom (MLO) of Citrus
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PARASITE PLANTS
Arceuthobium spp. (non-European)
Details of the requirements of the Order and for the importation and keeping of plant pathogens may be obtained from:
Ministry of Agriculture, Fisheries and Food Plant Health Division 10 Whitehall Place London SW1A 2HH (Tel: 0171 270 8568) (Fax 0171 270 8330) and for technical enquiries from:
Ministry of Agriculture, Fisheries and Food Harpenden Central Science Laboratory Hatching Green Harpenden Herts AL5 2BD (Tel: 01582 715241) (Fax 01582 762178) and for Scotland from:
Scottish Office Agriculture and Fisheries Department Plant Health Branch Pentland House 47 Robbs Loan Edinburgh EH14 1TW (Tel: 0131 556 8400) (Fax 0131 244 6001) and for technical enquiries:
Scottish Agricultural Science Services Plant Health Branch East Craigs Edinburgh EH12 8NJ (Tel: 0131 556 8400) (Fax 0131 244 8940) for affairs in Northern Ireland
Department of Agriculture Northern Ireland Dundonald House Upper Newtonards Road Belfast BT4 3SB
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Forestry Commission Plant Health Branch 231 Corstorphine Road Edinburgh EH12 7AT (Tel: 0131 334 0303) (Fax: 0131 334 3047)
In certain cases, licences may also be required to import alien isolates or strains of plant pathogens or pests which occur here but which are likely to be of differing pathogenicity or host range from those occurring naturally within this country.
It is the responsibility of the user to determine whether or not the organism to be used is a plant pathogen or pest, whether or not it is established in Great Britain, and to apply to the Department of Agriculture for a licence as appropriate. In such cases, the user will be helped to select lower risk organisms where possible.
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APPENDIX 21 REPORTING OCCUPATIONAL INJURIES, DISEASES AND DANGEROUS OCCURRENCES
1 The Reporting of Injuries, Diseases and Dangerous Occurrences Regulations 1985 (RIDDOR) impose a duty to report certain dangerous occurrences, occupational injuries and diseases. The obligation to report is placed on employers, the self-employed and people in control of premises. Injuries to both employees and members of the public associated with occupation are reportable but diseases are reportable only when suffered by an employee. The events have to be reported to the enforcing authority responsible for the premises where the event occurred.
Injuries 2 Reportable injuries are those which arise out of an accident at or in connection with work and which cause either:
(a) the death of any person; or
(b) a major injury to any person; or
(c) an employee to be absent from or incapable of doing their normal work for more than three days. Days which are not normally worked for example Saturdays and Sundays count towards the three days incapacity if on those days the injured person is unable to do their normal work.
3 Major injuries are defined in the Regulations. It is important to note that cases of acute ill health which can be linked to a single accident are reportable as a major injury. For example, where a laboratory worker was diagnosed as having hepatitis B following an accident in a research facility that would be reportable as a major injury.
4 Fatal and major injuries must be notified by telephone as soon as they come to the attention of the responsible person. Written confirmation on the approved form, F2508, must be sent within seven days of the incident. Other reportable injuries must be notified in writing on the approved form, F2508, within seven days of the incident.
Diseases 5 Cases of occupational disease are reportable when
(a) an employer receives written notice from a medical practitioner that an employee is suffering from a disease listed in the Regulations; and
(b) the employee has been involved in a work activity listed against that disease.
Reports should be made on an approved form, F2508A.
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Dangerous occurrences 6 Dangerous occurrences are accidents which have caused no injuries but which have caused serious damage to plant or equipment and which had the potential to cause very serious injuries. Only those dangerous occurrences listed in the Regulations are reportable. They include any uncontrolled or accidental release or escape of any pathogen or substance from any apparatus or equipment. Dangerous occurrences should be notified immediately and confirmed in writing on form F2508 within seven days of the incident.
7 This brief summary of the requirements is by no means a comprehensive or exhaustive statement of the law. More detailed information is provided in the HSE publication A guide to The Reporting of Injuries; Diseases and Dangerous Occurrences Regulations 1985 HS(R) 23. The free leaflet Reporting under RIDDOR (HSE 24) provides a useful aide memoire.
8 RIDDOR is currently under review. It is anticipated that changes to the regulations proposed in several public consultations on separate aspects of the legislation will take effect in 1996. There is likely to be, among other things, simplification of the definition of major injury, simplification of the reporting procedures and extension of the list of occupational diseases in line with the European Schedule of Industrial Diseases.
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APPENDIX 22 NOTIFICATION OF FIRST USE OF BIOLOGICAL AGENTS; CONSIGNMENT OF AGENTS IN PART V SCHEDULE 9 OF COSHH; PROVISION OF DIAGNOSTIC SERVICES CONCERNING AGENTS IN PART V
1 The Health and Safety (Dangerous Pathogens) Regulations 1981 dealt with the notification of work with certain particularly hazardous pathogens such as smallpox and Lassa fever viruses. Those Regulations have now been revoked in favour of a new and more wide-ranging system of notification imposed by the European Community Directive on biological agents now implemented in the new COSHH Regulations (COSHH 1994).
Summary 2 There is now a requirement for notification of the HSE 30 days in advance of ‘first use’ of all biological agents in Hazard Groups 2, 3 and 4. Furthermore, consignment and importation of agents in Part V of Schedule 9 of COSHH must also be notified as must the provision of all types of diagnostic service in relation to those agents. The new duties relating to notification appear in paragraphs 12 and 13 in Schedule 9 of COSHH.
First use 3 ‘First use’ means work with or storage of a biological agent where no such work has been conducted before. Notification would be required where, for example, a new laboratory is set up or exceptionally an existing laboratory has not worked before with any of the agents in one group or another. ‘Use’ should be taken to exclude activities in which agents are incidentally present for example hepatitis viruses or HIV in specimens for serological examination (but see below under Part V). In practice, the great majority of microbiology laboratories will have worked with a number of agents in Hazard Groups 2 and 3 at some time and therefore notification will not be necessary for them. Where it does apply, only the group need normally be notified, but the actual agents to be used or stored at the time of this first involvement with a group should also be identified.
Who and what to notify 4 An official notification form (CBA1) must be used for notifying the Health and Safety Executive 30 days in advance of the activities described in paragraph 2 above. The same multi-part form provides for first use, notification of consignment or importation of the agents listed in Part V of Schedule 9 and the intention to provide a diagnostic service in connection with those agents.
Exclusions 5 If notification of the use of a named biological agent has been made under the Genetically Modified Organisms (Contained Use) Regulations 1992, then no further action is necessary. Furthermore, first use of any biological agent concerns only those sites where no such work has been carried out before COSHH 1994 came into force (but see also paragraph 8 onwards concerning subsequent agents in Part V and consignment or importation of agents in Part V).
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Research and diagnostic 6 Many types of diagnostic and research work, for example in work and clinical care of haematology, immunology or clinical chemistry laboratories, may involve patients and animals material which contains biological agents but if there is no intention to propagate or concentrate those agents then they are excluded from the requirement to notify except where material contains or may contain agents in Part V of Schedule 9 of COSHH. There is no need to notify if the work involves the clinical care of infected patients or handling naturally infected animals whether or not the agents concerned are in Part V.
7 In the great majority of cases, therefore, ‘first use’ means work with ( ie propagation or concentration) or storage of biological agents and will apply principally to microbiology, virology, mycology and parasitology laboratories and to industry where any agent in Groups 2, 3 and 4 may be handled.
Diagnostic services - 8 If there is an intention to provide any form of laboratory service Part V agents (diagnosis and patient management) in relation to patients infected with any of the agents listed in Part V of Schedule 9 (whether or not it involves propagation or concentration), the requirement to notify applies. Those few laboratories already providing such a service and having notified under the Health and Safety (Dangerous Pathogens) Regulations 1981 do not need to re-notify.
Subsequent 9 Notification of the use or storage of subsequent biological agents is notification required in certain circumstances:
each subsequent agent in Part V of Schedule 9 of COSHH 1994 (ie if a particular agent in Part V has not been notified before or a new agent is provisionally classified by the employer in Group 4);
each subsequent Group 3 agent if it does not appear in the Approved List in the Categorisation of biological agents according to hazard and categories of containment and is provisionally classified by the employer;
when carrying out a diagnostic service in relation to agents in Part V described as Group 4 agents, each subsequent agent, if there is an intention to propagate or concentrate an agent that does not appear the Approved List of biological agents, ie one that an employer has provisionally classified in Group 4.
Consignment of agents 10 If there is the intention to consign or import any agent in Part V, notification is required 30 days in advance except where the material is being sent solely for the purpose of making a diagnosis, is in any material being sent solely for disposal (including a body), or is in a human patient or animal being transported for the purpose of medical treatment.
11 Any changes to processes or procedures which would affect health and safety at work and render an earlier notification invalid, should be notified to The Health and Safety Executive at the address below.
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The notification form 12 The official notification form, CBA1 is available from the following address. When completed, it should be returned 30 days before work is begun or consignment of Part V agents is arranged.
Health and Safety Executive Health Policy Division B1 7th Floor, South Wing Rose Court 2 Southwark Bridge London SE1 9HS
Biological agents in 1 All Hazard Group 4 biological agents1. Part V of Schedule 9 of COSHH 1994 2 Rabies virus.
3 Simian herpes B virus.
4 Venezuelan equine encephalomyeltis virus.
5 Tick-borne encephalitis group viruses in Group 3.
6 Monkeypox virus.
7 Mopeia virus.
1 Including those Group 4 agents not appearing in the Approved List of biological; agents and those provisionally classified by an employer...... Page 133 Advisory Committee on Dangerous Pathogens ......
APPENDIX 23 APPROVED LIST OF BIOLOGICAL AGENTS
Preface The categorisation of biological agents on the following pages is an Approved List made under Section 15 of the Health and Safety at Work etc Act 1974. The Control of Substances Hazardous to Health Regulations 1994 impose requirements by reference to this Document, which requirements are therefore legally binding. The Notice of Approval signed by the Secretary of the Health and Safety Commission signals its legal status. The list implements European Community Directive 93/88/EEC which contains a Community classification of biological agents.
COSHH at Schedule 9 paragraph 8(4)(b) demands amongst other things ‘... (containment) level 3 (as a minimum) for activities involving the handling of a (ie any) Group 3 biological agent ...’ . However, those intending to work with agents in Group 3 should read the certificate of exemption accompanying the Approved List. The Schedule to the certificate specifies those agents for which derogation from full Containment Level 3 is presently permitted on condition that there is adherence to the guidance in the publications named in the certificate. It should be noted that this exemption may be used by all employers and that no individual certificate relating to any single establishment or any individual work activity is necessary.
Genetically modified biological agents do not appear as such in this categorisation although the wild-type species from which many of them are derived are listed if they are capable of causing infection in otherwise healthy humans. GMO are classified under a different system in which agents fall into either Group I or Group II (see A guide to the Genetically Modified Organisms (Contained Use) Regulations 1992). Schedule 2 of those Regulations gives the criteria for the classification of genetically modified organisms. Any agent retaining harmful properties for humans (or the environment) after modification would fall into Group II.
Enquiries relating to the Approved List may be addressed to the ACDP Secretariat at HSE, Room 703, Rose Court, 2 Southwark Bridge London SE1 9HS.
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CATEGORISATION OF BIOLOGICAL AGENTS ACCORDING TO HAZARD AND CATEGORIES OF CONTAINMENT
NOTICE OF APPROVAL
By virtue of section 15(4)(a) of the Health and Safety at Work etc. Act 1974 and pursuant to paragraph 3(1) of Schedule 9 to the Control of Substances Hazardous to Health Regulations 1994, the Health and Safety Commission has on 26 April 1995 approved this document entitled, Categorisation of biological agents according to hazard and categories of containment (4th Edition) (Approved List (Second Edition)) for the purpose of said Schedule. This Document shall have effect from 1st December 1995 and on that date the Categorisation of biological agents according to hazard and categories of containment (‘Approved List’) (approved by the Health and Safety Commission on 9th November 1994 for the purpose of the aforementioned Schedule) shall cease to have effect.
Signed T. A. GATES
Secretary to the Health and Safety Commission
Dated this 26th day of September 1995
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THE HEALTH AND SAFETY AT WORK ETC ACT 1974
THE CONTROL OF SUBSTANCES HAZARDOUS TO HEALTH REGULATIONS 1994
CERTIFICATE OF EXEMPTION No. 5 OF 1995
1 In pursuance of powers conferred on it by paragraph (1) of regulation 14 of the Control of Substances Hazardous to Health Regulations 19941 (‘the Regulations’) and being satisfied as required by paragraph (2) of that regulation, the Health and Safety Executive hereby exempts, subject to the condition specified in paragraph 2 below, any employer who uses any of the biological agents listed in the Schedule to this certificate, in the course of any of the activities specified in sub-paragraph (3) of paragraph 8 of Schedule 9 of the Regulations from the duty imposed on him by sub-paragraph (1) of the said paragraph insofar as it requires him to take into account the minimum containment level specified in sub-paragraph (4) of the said paragraph.
2 The condition referred to in paragraph 1 above is that the employer, when working with any of the agents listed in the Schedule to this certificate, observes the conditions of containment and the recommended control measures in the apprpriate publications(s) listed below:
Categorisation of biological agents according to hazard and categories of containment 1995 ISBN 0 7176 1038 1;
Precautions for work with animal and human transmissible spongiform encephalopathies 1994 HMSO ISBN 0 11 321805 2;
Protection against blood-borne infections in the workplace - HIV and hepatitis 1995 HMSO ISBN 0 11 321953 9.
3 This certificate shall come into force on the 1st day of December 1995
Dated this 17th day of October 1995
Signed Dr PJ GRAHAM
The holder of the post designated, a person authorised by the Health and Safety Executive to act in that behalf.
1SI 1994/3246...... Page 136 Advisory Committee on Dangerous Pathogens ......
Schedule: Biological BACTERIA PARASITES agents in Hazard Group 3 subject to 1 Mycobacterium ulcerans 17 Echinococcus granulosus exemption 2 Mycobaterium microti 18 Echinoococcus multilocularis
3 Salmonella typhi 19 Echinococcus vogeli
4 Salmonella paratyphi 20 Leishmania braziliensis
5 Shigella dysenteriae 21 Leishmania donovani
VIRUSES 22 Plasmodium falciparum
6 hepatitis B virus 23 Taenia solium
7 hepatitis C virus 24 Trypanosoma brucei rhodesiense 8 hepatitis D virus
9 hepatitis E virus
10 human immunodeficiency viruses
11 human T-cell lymphotropic viruses
12 blood-borne hepatitis viruses not yet identified
13 the agent of Creutzfeldt-Jakob disease
14 the agent of Gerstmann-Sträussler-Scheinker syndrome
15 the agent of kuru
16 simian immunodeficiency virus
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Approved List of INTRODUCTION biological agents 1 The Approved List of biological agents should be read in conjunction with the Control of Substances Hazardous to Health Regulations 1994 and in particular Schedule 9 thereof: ‘Special provisions relating to biological agents’.
2 Agents appearing in the Approved List are categorised on the basis of their ability to cause disease by infection. Only agents in Groups 2, 3 and 4 are listed. Those not listed in these groups are not implicitly classified in Group 1.
3 In allocating agents to a Hazard Group in the Approved List, no account is taken of particular effects on those whose susceptibility to infection may be affected for one or other reason such as pre-existing disease, medication, compromised immunity, pregnancy or breast-feeding. Additional risk to such workers should be considered as part of the risk assessment required by COSHH 1994. In the case of women who are new or expectant mothers, the assessment should also be in conformity with the Management of Health and Safety at Work (Amendment) Regulations 1994.
4 If more than one species in any particular genus is known to be pathogenic to humans, the most prominent of these is generally named, together with a wider reference (‘spp’) to the fact that other species of the same genus may be hazardous. However, if a whole genus is indicated in this way, it is implicit that species and strains that are non-pathogenic to humans are excluded.
5 When a strain of a biological agent is attenuated or has lost known virulence genes, then the containment required by the classification of its parent strain need not necessarily apply. Subject to assessment appropriate to the risk in the workplace, employers must classify such strains (see COSHH 1994 at Schedule 9, paragraph 3 (3) and (4)). Examples of when containment measures may be modified include when a strain is used as a product or as part of a product for prophylactic or therapeutic purposes.
6 All viruses which have been isolated from humans and which have not been assessed and allocated to a Hazard Group in the list are to be classified in Hazard Group 2 as a minimum, except where there is evidence that they are unlikely to cause disease in humans.
7 The requirements as to containment consequent upon the classification of parasites apply only to the stages in the life cycle of the parasite in which it is liable to be infectious for humans.
8 The list also gives a separate indication in cases where biological agents are capable of causing allergic or toxic reactions, where an effective vaccine is available, or where a list of exposed workers shall be kept for 40 years
...... Page 138 Advisory Committee on Dangerous Pathogens ...... following the last known exposure (see paragraph 11 (3) Schedule 9 of COSHH 1994). These indications are shown by the following notations:
A: possible allergic effects; D: list of workers exposed to this biological agent to be kept for 40 years after the end of the last known exposure; T: toxin production; v: effective vaccine available.
(Exposure in work with any Group 3 or Group 4 biological agent entails keeping records of those exposed for at least 10 years; see paragraph 11 (1) of Schedule 9, COSHH 1994).
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Biological agent Classification Notes
BACTERIA
Acinetobacter calcoaceticus 2 Acinetobacter lwoffi 2 Actinobacillus actinomycetemcomitans 2 Actinomadura madurae 2 Actinomadura pelletieri 2 Actinomyces gerencseriae 2 Actinomyces israelii 2 Actinomyces pyogenes 2 Actinomyces spp 2 Aeromonas hydrophila 2 Alcaligenes spp 2 Arcanobacterium haemolyticum (Corynebacterium haemolyticum) 2 Arizona spp 2 Bacillus anthracis 3 V Bacillus cereus 2 Bacteroides fragilis 2 Bacteroides spp 2 Bartonella bacilliformis 2 Bartonella quintana (Rochalimaea quintana) 2 Bartonella spp (Rochalimaea spp) 2 Bordetella bronchiseptica 2 Bordetella parapertussis 2 Bordetella pertussis 2 V Borrelia burgdorferi 2 Borrelia duttonii 2 Borrelia recurrentis 2 Borrelia spp 2 Brucella abortus 3 Brucella canis 3 Brucella melitensis 3 Brucella suis 3 Burkholderia cepacia 2 Burkholderia mallei (Pseudomonas mallei) 3 Burkolderia pseudomallei (Pseudomonas pseudomallei) 3 Burkholderia spp 2 Campylobacter fetus 2 Campylobacter jejuni 2 Campylobacter spp 2 Cardiobacterium hominis 2
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Biological agent Classification Notes
Chlamydia pneumoniae 2 Chlamydia psittaci (non avian strains) 2 Chlamydia psittaci (avian strains) 3 Chlamydia trachomatis 2 Clostridium botulinum 2 T, V Clostridium perfringens 2 Clostridium tetani 2 T, V Clostridium spp 2 Corynebacterium diphtheriae 2 T, V Corynebacterium minutissimum 2 Corynebacterium pseudotuberculosis 2 Corynebacterium spp 2 Coxiella burnetii 3 Edwardsiella tarda 2 Ehrlichia sennetsu (Rickettsia sennetsu) 3 Ehrlichia spp 3 Eikenella corrodens 2 Enterobacter aerogenes/cloacae 2 Enterobacter spp 2 Enterococcus spp 2 Erysipelothrix rhusiopathiae 2 Escherichia coli (with the exception of non-pathogenic strains) 2 Flavobacterium meningosepticum 2 Fluoribacter bozemanae (formerly Legionella) 2 Francisella tularensis (Type A) 3 V Francisella tularensis (Type B) 2 Fusobacterium necrophorum 2 Fusobacterium spp 2 Gardnerella vaginalis 2 Haemophilus ducreyi 2 Haemophilus influenzae 2 Haemophilus spp 2 Helicobacter pylori 2 Klebsiella oxytoca 2 Klebsiella pneumoniae 2 Klebsiella spp 2 Legionella pneumophila 2 Legionella spp 2 Leptospira interrogans (all serovars) 2 Listeria ivanovii 2 Listeria monocytogenes 2 Moraxella catarrhalis 2 Moraxella lacunata 2
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Biological agent Classification Notes
Morganella morganii 2 Mycobacterium africanum 3 V Mycobacterium avium/intracellulare 3 Mycobacterium bovis (BCG strain) 2 Mycobacterium bovis 3 V Mycobacterium chelonae 2 Mycobacterium fortuitum 2 Mycobacterium kansasii 3 Mycobacterium leprae 3 V Mycobacterium malmoense 3 Mycobacterium marinum 2 Mycobacterium microti 3 Mycobacterium paratuberculosis 2 Mycobacterium scrofulaceum 3 Mycobacterium simiae 3 Mycobacterium szulgai 3 Mycobacterium tuberculosis 3 V Mycobacterium ulcerans 3 Mycobacterium xenopi 3 Mycoplasma hominis 2 Mycoplasma pneumoniae 2 Neisseria elongata 2 Neisseria gonorrhoeae 2 Neisseria meningitidis 2 V Nocardia asteroides 2 Nocardia brasiliensis 2 Nocardia farcinica 2 Nocardia nova 2 Nocardia otitidiscaviarum 2 Nocardia spp 2 Pasteurella multocida 2 Pasteurella spp 2 Peptostreptococcus anaerobius 2 Peptostreptococcus spp 2 Plesiomonas shigelloides 2 Porphyromonas spp 2 Prevotella spp 2 Proteus mirabilis 2 Proteus penneri 2 Proteus vulgaris 2 Providencia alcalifaciens 2 Providencia rettgeri 2 Providencia spp 2 Pseudomonas aeruginosa 2
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Biological agent Classification Notes
Pseudomonas mallei - see Burkholderia mallei 3 Pseudomonas pseudomallei - see Burkholderia pseudomallei 3 Rhodococcus equi 2 Rickettsia akari 3 Rickettsia canada 3 Rickettsia conorii 3 Rickettsia montana 3 Rickettsia prowazekii 3 Rickettsia rickettsii 3 Rickettsia tsutsugamushi 3 Rickettsia sennetsu (see Ehrlichia sennetsu) 3 Rickettsia typhi (Rickettsia mooseri) 3 Rickettsia spp 3 Rochalimaea quintana - see Bartonella quintana 2 Rochalimaea spp 2 Salmonella arizonae 2 Salmonella enteritidis 2 Salmonella (other serovars) 2 Salmonella paratyphi A,B,C 3 Salmonella typhi 3 V Salmonella typhimurium 2 Serpulina spp 2 Serratia liquefaciens 2 Serratia marcescens 2 Shigella boydii 2 Shigella dysenteriae (Type 1) 3 T Shigella dysenteriae (other than Type 1) 2 Shigella flexneri 2 Shigella sonnei 2 Staphylococcus aureus 2 T Stenotrophomonas maltophilia 2 Streptobacillus moniliformis 2 Streptococcus pneumoniae 2 Streptococcus pyogenes 2 Streptococcus suis 2 Streptococcus spp 2 Treponema carateum 2 Treponema pallidum 2 Treponema pertenue 2 Treponema spp 2
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Biological agent Classification Notes
Ureaplasma urealyticum 2 Vibrio cholerae (including El Tor) 2 T, V Vibrio parahaemolyticus 2 Vibrio spp 2 Yersinia enterocolitica 2 Yersinia pestis 3 V Yersinia pseudotuberculosis 2 Yersinia spp 2
VIRUSES
ARENAVIRIDAE Amapari 2 Flexal 3 Guanarito 4 Ippy 2 Junin 4 Lassa fever 4 Latino 2 lymphocytic choriomeningitis 3 Machupo 4 Mobola 2 Mopeia 3 Parana 2 Pichinde 2 Sabia 4 Tamiami 2 ASTROVIRIDAE 2 BUNYAVIRIDAE Akabane 3 Bunyamwera 2 California encephalitis 2 Germiston 3 Oropouche 3 HANTAVIRUSES Hantaan (Korean haemorrhagic fever) 3 Prospect Hill 2 Puumala 2 Seoul 3 Sin Nombre (formerly Muerto Canyon) 3 Other Hantaviruses 2 NAIROVIRUSES Bhanja 3 Crimean/Congo haemorrhagic fever 4 Hazara 2
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Biological agent CIassification Notes
PHLEBOVIRUSES Rift valley fever 3 V Sandfly fever 2 Toscana 2 Uukuviruses 2 Other Bunyaviridae known to be pathogenic 2 CALICIVIRIDAE hepatitis E 3 Norwalk 2 Other Caliciviridae 2 CORONAVIRIDAE 2 FILOVIRIDAE Ebola Reston 4 Ebola Siena 4 Ebola Sudan 4 Ebola Zaire 4 Marburg 4 FLAVIVIRIDAE Flaviviruses Dengue viruses Types 1-4 3 Israel turkey meningitis 3 Japanese B encephalitis 3 V Murray Valley encephalitis 3 Rocio 3 Sal Vieja 3 San Perlita 3 Spondweni 3 St Louis encephalitis 3 Wesselsbron 3 West Nile fever 3 Yellow fever 3 V Tick-borne virus group Absettarov 3 V Hanzalova 3 V Hypr 3 V Kumlinge 3 Kyasanur forest disease 4 V Louping ill 3 V Negishi 3 Omsk 4 V Powassan 3 Russian spring summer encephalitis 4 V Hepatitis C group viruses hepatitis C 3 D Other flaviviruses known to be pathogenic 2
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Biological agent Classification Notes
Hepadnaviridae hepatitis B 3 V, D hepatitis D (delta) 3 V, D HERPESVIRIDAE Cytomegalovirus 2 Epstein-Barr virus 2 Herpes simplex types 1 and 2 2 Herpes virus varicella-zoster 2 Herpesvirus simiae (B virus) 3 Human herpesvirus type 6 - HHV6 2 Human herpesvirus type 7 - HHV7 2 ORTHOMYXOVIRIDAE Influenza types A, B and C2 2 V Tick-borne orthomyxoviridae Dhori and Thogoto 2 PAPOVAVIRIDAE BK and JC viruses 2 Human papillomaviruses 2 PARAMYXOVIRIDAE Measles 2 V Mumps 2 V Newcastle disease 2 Parainfluenza (Types 1 to 4) 2 Respiratory syncytial virus 2 PARVOVIRIDAE Human parvovirus (B19) 2 PICORNAVIRIDAE Acute haemorrhagic conjunctivitis virus (AHC) 2 Coxsackieviruses 2 Echoviruses 2 Polioviruses 2 V Rhinoviruses 2 Hepatoviruses hepatitis A (human enterovirus type 72) 2 V POXVIRIDAE Buffalopox 2 Cowpox1 2 Milker’s nodes 2 Molluscum contagiosum 2 Monkeypox 3 V Orf 2 Vaccinia2 2 Variola (major and minor)3 4 V Yatapox (Tana and Yaba) 2
1 Including strains isolated from domestic cats and captive exotic species, for example elephants, cheetahs. 2 Including strains originally classified as rabbitpox. 3 All strains including whitepox virus...... Page 146 Advisory Committee on Dangerous Pathogens ......
Biological agent Classification Notes
REOVIRIDAE Coltivirus 2 Human rotaviruses 2 Orbiviruses 2 Reoviruses 2 RETROVIRIDAE Human immunodeficiency viruses 3 Human T-cell lymphotropic viruses (HTLV) types 1 and 2 3 D Simian immunodeficiency virus 3 RHABDOVIRIDAE Duvenhage 2 V Pity 3 Rabies 3 V Vesicular stomatitis 2 TOGAVIRIDAE Alphaviruses: Bebaru 2 Chikungunya 3 Eastern equine encephalomyelitis 3 Everglades 3 Getah 3 Mayaro 3 Middleburg 3 Mucambo 3 Ndumu 3 O’nyong-nyong 3 Ross river 2 Sagiyama 3 Semliki forest 3 Sindbis 2 Tonate 3 Venezuelan equine encephalomyelitis 3 Western equine encephalomyelitis 3 V Other known alphaviruses 3 V Rubiviruses: Rubella 2 V UNCLASSIFIED VIRUSES Blood-borne hepatitis viruses not yet identified 3 D Equine morbillivirus 3 UNCONVENTIONAL AGENTS associated with: Creutzfeldt-Jakob disease 3 D Gerstmann-Sträussler-Scheinker syndrome 3 D Kuru 3 D
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Biological agent Classification Notes
PARASITES
Acanthamoeba castellanii 2 Acanthamoeba spp 2 Ancylostoma duodenale 2 Angiostrongylus cantonensis 2 Angiostrongylus costaricensis 2 Anisakis simplex 2 Ascaris lumbricoides 2 A Ascaris suum 2 A Babesia divergens 2 Babesia microti 2 Balantidium coli 2 Blastocystis hominis 2 Brugia malayi 2 Brugia pahangi 2 Brugia timori 2 Capillaria philippinensis 2 Capillaria spp 2 Clonorchis - see Opisthorchis Contracaecum osculatum 2 Cryptosporidium parvum 2 Cryptosporidium spp 2 Cyclospora cayetanensis 2 Cyclospora spp 2 Dicrocoelium dendriticum 2 Dientamoeba fragilis 2 Dipetalonema - see Mansonella 2 Diphyllobothrium latum 2 Dracunculus medinensis 2 Echinococcus granulosus 3 Echinococcus multilocularis 3 Echinococcus vogeli 3 Entamoeba histolytica 2 Enterobius vermicularis 2 Enterocytozoon bieneusi 2 Fasciola gigantica 2 Fasciola hepatica 2 Fasciolopsis buski 2 Giardia lamblia (Giardia intestinalis) 2 Heterophyes spp 2 Hymenolepis diminuta 2 Hymenolepis nana 2 lsopora belli 2 Leishmania aethiopica 2 Leishmania brasiliensis 3
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Biological agent Classification Notes
Leishmania donovani 3 Leishmania mexicana 2 Leishmania peruviana 2 Leishmania major 2 Leishmania tropica 2 Leishmania spp 2 Loa loa 2 Mansonella ozzardi 2 Mansonella perstans 2 Mansonella streptocerca 2 Metagonimus spp 2 Naegleria fowleri 2 Necator americanus 2 Onchocerca volvulus 2 Opisthorchis felineus 2 Opisthorchis sinensis (Clonorchis sinensis) 2 Opisthorchis viverrini (Clonorchis viverrini) 2 Opisthorchis spp 2 Paragonimus westermani 2 Paragonimus spp 2 Plasmodium falciparum 3 Plasmodium spp (human & simian) 2 Pseudoterranova decipiens 2 Sarcocystis suihominis 2 Schistosoma haematobium 2 Schistosoma intercalatum 2 Schistosoma japonicum 2 Schistosoma mansoni 2 Schistosoma mekongi 2 Schistosoma spp 2 Strongyloides stercoralis 2 Strongyloides spp 2 Taenia saginata 2 Taenia solium 3 Toxocara canis 2 Toxocara cati 2 Toxoplasma gondii 2 Trichinella nativa 2 Trichinella nelsoni 2 Trichenella pseudospiralis 2 Trichinella spiralis 2 Trichomonas vaginalis 2 Trichostrongylus orientalis 2 Trichostrongylus spp 2
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Biological agent Classification Notes
Trichuris trichiura 2 Trypanosoma brucei brucei 2 Trypanosoma brucei gambiense 2 Trypanosoma brucei rhodesiense 3 Trypanosoma cruzi 3 Trypanosoma rangeli 2 Wuchereria bancrofti 2
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Biological agent CIassification Notes
FUNGI
Aspergillus fumigatus 2 A Blastomyces dermatitidis 3 (Ajellomyces dermatitidis) Candida albicans 2 A Candida spp 2 Coccidioides immitis 3 A Cryptococcus neoformans var neoformans 2 A (Filobasidiella neoformans var neoformans) Cryptococcus neoformans var gattii 2 A (Filobasidiella bacillispora) Emmonsia parva var parva 2 Emmonsia parva var crescens 2 Epidermophyton fioccosum 2 A Fonsecaea compacta 2 Fonsecaea pedrosoi 2 Histoplasma capsulatum var capsulatum 3 (Ajellomyces capsulatus) Histoplasma capsulatum var duboisii 3 Histoplasma capsulatum var farcinimosum 3 Madurella grisea 2 Madurella mycetomatis 2 Microsporum spp 2 A Neotestudina rosatii 2 Paracoccidioides brasiliensis 3 Penicillium marneffei 3 A Sporothrix schenckii 2 Trichophyton rubrum 2 Trichophyton spp 2 Xylohypha bantiana 2
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BIBLIOGRAPHY
Bergey’s manual of systematic bacteriology. Volume 1 Krieg, NR and Holt JG 1984 ISBN 0 683 04108 8; Volume 2 Sneath, PH, Mair NS et al 1986 ISBN 0 683 07893 3; Volume 3 Staley, JT, Bryant MP et al 1989 ISBN 0 683 07908 5; Volume 4 Williams ST, Sharpe ME et al 1989 ISBN 0 638 09061 5
Benenson A S (ed) Control of communicable diseases in man 1990 American Public Health Association ISBN 0 875 53170 9
Collins C H Laboratory-acquired infections - History, incidence, Causes and Prevention 1993 (3rd edition) Butterworth-Heinemann Ltd ISBN 0 7506 0642 8
Health and Safety Commission’s Education Services Advisory Committee Health and safety in animal facilities 1992 HSE Books ISBN 0 11 886353 3
Health and Safety Commission’s Health Services Advisory Committee Safety in Health Service Laboratories: Safe working and the prevention of infection in clinical laboratories 1991 HSE Books ISBN 0 11 885446 1
Francki R I B, Fauquet C M, Knudson D L and Brown F (eds) Classification and nomenclature of viruses - Fifth report of the international committee on taxonomy of viruses 1991 Archives of Virology Suppl. 2 Springer-Verlag ISBN 0 387 82286 0
Medical Research Council Nomenclature of fungi pathogenic to man and animals 1977 HMSO ISBN 0 114 50037 1
Noble E R and Noble G A Parasitology: the biology of animal parasites 1989 (6th edition) Lea and Febigier ISBN 0 812 11155 9
Shooter R A Report of the investigation into the cause of the 1978 Birmingham smallpox occurrence 1980 HC 668 HMSO ISBN 0 102 66880 9
Skerman,VBD, McGovern V et al Approved lists of bacteria/ names 1989 International Committee on Systematic Bacteriology ISBN 1 55581014 4
World Health Organisation Approved names of biomedical/y important bacteria 1981 WHO Terminology Circular TXB-1 (TER/81.1 November 1981)
World Health Organisation Laboratory Biosafety Manual 1993 (2nd edition) Geneva ISBN 9 241 54450 3
Zuckerman A J, Banatvala J E and Pattison J R (eds) Principles and practice of clinical virology 1990 (2nd edition) John Wiley and Sons ISBN 0 471 92274 9
Printed in the UK for the Health and Safety Executive C50 10/95
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