APP203705 Staff Assessment Report.Pdf

EPA advice for application APP203705

Staff Assessment Report

February 2019

APP203705: To determine the new organism status of:

Tremovirus A (Avian encephalomyelitis virus)

Chicken anaemia virus (CAV or CIAV)

Fowlpox virus

Gallid alphaherpesvirus 2 (Marek’s disease serotype 1 virus)

Gallid alphaherpesvirus 2 (Marek’s disease serotype 2 virus)

Maleagrid alphaherpesvirus 1 (Marek’s disease serotype 3 virus)

Eimeria acervulina, E. brunetti, E. necatrix, E. tenella and E. maxima

Purpose To determine if various live poultry organisms in vaccines are new organisms under section 26 of the HSNO Act

Application number APP203705

Application type Statutory determination

Applicant Pacificvet Limited

Date formally received 23 January 2019

Executive Summary and Recommendation

Application APP203705, submitted by Pacificvet Limited, seeks a determination on the new organism status of:

 Tremovirus A (Avian encephalomyelitis virus)

 Chicken anaemia virus (CAV or CIAV)

 Fowlpox virus

 Gallid alphaherpesvirus 2 (Marek’s disease serotype 1 virus)

 Gallid alphaherpesvirus 2 (Marek’s disease serotype 2 virus)

 Maleagrid alphaherpesvirus 1 (Marek’s disease serotype 3 virus)

 Eimeria acervulina

 Eimeria brunetti

 Eimeria necatrix

 Eimeria tenella

 Eimeria maxima

After reviewing all of the available information and completing a literature search concerning the organisms, EPA staff recommend that Tremovirus A (Avian encephalomyelitis virus), Chicken anaemia virus (CAV or CIAV), Fowlpox virus, Gallid alphaherpesvirus 2 (Marek’s disease serotype 1 virus), Gallid alphaherpesvirus 2 (Marek’s disease serotype 2 virus), Maleagrid alphaherpesvirus 1 (Marek’s disease serotype 3 virus), Eimeria acervulina, E. brunetti, E. necatrix, E. tenella and E. maxima are not new organisms for the purpose of the HSNO Act based on evidence that these organisms have been identified and present in New Zealand since before 29 July 1998 when the HSNO Act came into effect.

EPA advice for application APP203705

Table of Contents Introduction and background ……………………………………………………………4 Organism description…………………………………………………………………………4 Review of information………………………………………………………………………14 Recommendation………………………………………………………………………...…...15 Appendix 1: Correspondence with ACVM..…………………………………...…...16 References…………………………………………………………………………………….....18 Appendix 2: Decision pathway……..…………………………………………………..20

Introduction and background On 14 September 2018, Pacificvet Limited applied to the EPA under section 26 of the HSNO Act seeking a determination on the new organism status of Tremovirus A (Avian encephalomyelitis virus), Chicken anaemia virus (CAV or CIAV), Fowlpox virus, Gallid alphaherpesvirus 2 (Marek’s disease serotype 1 virus), Gallid alphaherpesvirus 2 (Marek’s disease serotype 2 virus), Maleagrid alphaherpesvirus 1 (Marek’s disease serotype 3 virus), Eimeria acervulina, E. brunetti, E. necatrix, E. tenella and E. maxima.

The EPA requested comment on the application from the Department of Conservation (DOC) and the Ministry for Primary Industries (MPI).

MPI did not make any comments on the application but confirmed the registration of vaccines under the ACVM Act.

DOC stated that the evidence presented by the applicant clearly indicated that the organisms were present in New Zealand prior to 1998 and therefore, should not be listed as new organisms.

The Agricultural Compounds and Veterinary Medicines (ACVM) group of MPI confirmed the approved registrations of the vaccines referred to in this application (Appendix 1).

The applicant considers these species as not new organisms and to support this claim, the applicant provided evidence to demonstrate that each of these organisms are present in New Zealand. The evidence consisted of the identification and use of these microorganisms in live attenuated vaccines in New Zealand since before 29 July 1998 when the HSNO Act came into effect. In addition, the applicant provided evidence to support these microorganisms being present in New Zealand based on scientific literature dating back to the 1970s and the ubiquitous nature of these organisms due to the widespread cases of infection and live attenuated vaccine usage around the world.

Section 2A(1) of the HSNO Act prescribes that a new organism is, in part, an organism belonging to a species that was not present in New Zealand immediately before 29 July 1998. It is against this criterion that we evaluated the evidence available for the organisms in the application.

Description of organisms

Tremovirus A (Avian encephalomyelitis virus)

Taxonomic Unit Classification

Group Group IV ((+)ssRNA)

Order Picornavirales

Family Picornaviridae

EPA advice for application APP203705

Genus Tremovirus

Species Tremovirus A

Common name Avian encephalomyelitis virus (AEV)

Tremovirus A, also known as Avian encephalomyelitis virus (AEV), causes avian encephalomyelitis in chicks over 3-4 weeks old. It is characterised by ataxia, tremors and weakness or paralysis of the legs and was first reported by Jones in 1932. It was later demonstrated that AEV could be controlled by vaccination (Schaaf & Lamoreux, 1955). A vaccine was developed in 1961 using isolates from the brains of clinically affected two-week old chicks (Calnek, Taylor & Sevion, 1961). The subsequent use of vaccines had reduced the number of disease outbreaks (Howell, 1992).

AEV was first described in New Zealand by Howell and Bell (1987) and the disease was linked to a series of egg production drops in 1977 in the North Island. Between 1980 and 1982, pooled samples from 40 New Zealand laying flocks, all unvaccinated, were tested and AEV was detected in 47% of these flocks (Howell & Bell, 1987). Furthermore, AEV was described as endemic in New Zealand by Manktelow et al (1988). Following on from Howell and Bell’s discovery of AEV antibodies in 1987, Howell described the virus and its presence in New Zealand in 1992 (Howell, 1992).

Three live attenuated vaccines containing AEV have been developed and registered under the Agricultural Compounds and Veterinary Medicine (ACVM) Act (see Table 1 below). They have been historically used in New Zealand to combat AEV with the earliest vaccine, AE-VAC, having been developed, registered and used from 1970 onwards in New Zealand.

AEV has also been identified as a common endemic disease in chicken flocks in New Zealand by Watts in 2013 which, based on the evidence, suggests an ongoing presence of AEV in New Zealand.

Registered vaccines Table 1: Registered vaccines for avian encephalomyelitis virus under the ACVM Act (1997). Information taken from the MPI ACVM register.

Name Reg. date Reg. no Company Ingredients Strain

AE-VAC 15/01/1970 A001515 Pacificvet Ltd AEV Salsbury AE-67

AE-Poxine 11/10/1972 A004361 Pacificvet Ltd FPV1, AEV Salsbury AE-67

1 FPV: Fowlpox virus.

Nobilis AE + POX 26/11/1990 A006061 Schering-Plough FPV, AEV Unknown Animal Health Ltd

Chicken anaemia virus

Taxonomic Unit Classification

Group Group II (ssDNA)

Order Unassigned

Family Circoviridae

Genus Gyrovirus

Species Chicken anaemia virus syn. Chicken infectious anaemia virus (CAV or CIAV)

Common name See above

Chicken anaemia virus (CAV) or Chicken infectious anaemia virus (CIAV) is also known as gyrovirus. The virus was first described in Japan in 1979 (Yuasa, Taniguchi, & Yoshida) and has been isolated from chickens worldwide. Infection is characterised by anaemia, haemorrhages and atrophy of the thymus and spleen in 2-3 week old chicks. The virus is controlled by uniform inoculation with a live strain vaccine of CAV to breeding chickens during rearing and this prevents vertical transmission (Pattison et al. 2008).

The Ministry of Agriculture and Forestry (MAF) published a review in 1991 stating that chicken anaemia agent is present in New Zealand, is probably widespread and has been here for a while. The report advised that no specific safeguards against its presence in imported poultry meat are warranted (MacDiarmid, 1991). The presence of CAV was identified in New Zealand by Howell (1992) by isolating the virus from bone marrow, liver or lymphoid organs of infected young chicks. Similar results were found by isolating CAV DNA from infected chicks in 1992 (Tham & Stanislawek, 1992) and following on from this research, vaccination of poultry breeder flocks with a live vaccine has become standard practice in New Zealand. CAV was reportedly isolated from diseased birds in five separate flocks of broiler chickens in 1991 (Stanislawek & Howell, 1994). CAV has been identified as a common disease in chicken flocks in New Zealand (Watts, 2013).

Furthermore, the two live attenuated CAV vaccines listed below in Table 2 are in current use in New Zealand. These two vaccines have been registered in New Zealand under the ACVM Act.

EPA advice for application APP203705

Registered vaccines Table 2: Registered vaccines for chicken anaemia virus under the ACVM Act (1997). Information taken from the MPI ACVM register.

Name Reg. date Reg. no Company Ingredients Strain

AviPro Thymovac 05/02/2003 A009132 Pacificvet Ltd CAV Cux-1

Circomune 08/05/2017 A011331 Pacificvet Ltd CAV del-ros strain

Fowlpox virus

Taxonomic Unit Classification

Group Group I (dsDNA)

Order Unassigned

Family Poxviridae

Genus Avipoxvirus

Species Fowlpox virus

Common name See above

Fowlpox is an endemic disease in New Zealand caused by viruses of the genus Avipoxvirus, which affect many avian species. The term ‘fowlpox’ initially included all avian pox infections but now refers only to the disease in chickens (Tripathy & Reed, 2013). In chickens, fowlpox causes proliferative, wart-like lesions, respiratory distress and bulging of infra-orbital sinuses, and can lead to systemic infections (Manktelow, 1988). Fowlpox is of economic importance as it can cause a drop in egg production, slow growth and mortality. The disease is not significant to public health as it does not cause an infection in mammals (Tripathy & Reed, 2013). The virus transfers via skin and scabs from skin lesions or through inhalation or ingestion of virus- infected cells. The development of vaccines has minimised economic losses and regulated the disease in the poultry industry. In 1976 it was demonstrated that the attenuated fowlpox virus protects chickens against the fowlpox virus (Mayr & Danner, 1976).

Avipoxvirus infection is highly contagious in birds and in New Zealand at least three different strains of Avipoxvirus have been identified in a range of bird species. Recently these viruses have been gaining more attention in New Zealand after the spread of psittacinepox virus - a species within the genus Avipoxvirus (Gartrell et al. 2003). Fowlpox virus infection was identified to be common in laying units in the upper North Island (Howell, 1992, Manktelow et

al. 1988). In 1991 the MAF stated that avian pox viruses are widespread in New Zealand and imports of poultry meat products pose very little risk to New Zealanders as the virus cannot infect people (MacDiarmid, 1991).

Fowlpox has been listed as a disease of backyard poultry in New Zealand in 2013 by MPI (Watts, 2013). The phylogenetic analysis of avipoxvirus was summarised by Hye Jeong et al. (2011) and includes several references to support the presence of this virus in New Zealand after 1998. The first live attenuated vaccines, were registered in New Zealand in 1975 (Table 3). This demonstrates that fowlpox was present in New Zealand before 1998. Chick-N-Pox incorporates the Salsbury 946 strain of fowlpox virus isolated in 1960. The second live attenuated virus, Poxine, was registered in 1975 as well and incorporates the Salsbury strain isolated from the USA in 1938. Both vaccines have been used in New Zealand poultry flocks since their registrations (MPI ACVM register).

Registered vaccines Table 3: Registered vaccines for fowlpox virus under the ACVM Act (1997). Information taken from the MPI ACVM register.

Name Reg. date Reg. no Company Ingredients Strain

Chick-N-Pox 30/06/1975 A002780 Pacificvet Ltd FPV Salsbury 946

Poxine 30/06/1975 A002779 Pacificvet Ltd FPV Salsbury (isolated in 1938 in USA)

AE-Poxine 11/10/1982 A004361 Pacificvet Ltd FPV, AEV AEV: Salsbury-67

Gallid alphaherpesvirus 2 (Marek’s disease serotype 1 virus)

Taxonomic Unit Classification

Group Group I (dsDNA)

Order Herpesvirales

Family Herpesviridae

Subfamily Alphaherpesvirinae

Genus Mardivirus

Species Gallid alphaherpesvirus 2 (GaHV-2)

Common name Marek’s disease serotype 1 virus

EPA advice for application APP203705

Maleagrid alphaherpesvirus 1 (Marek’s disease serotype 3 virus)

Taxonomic Unit Classification

Group Group I (dsDNA)

Order Herpesvirales

Family Herpesviridae

Subfamily Alphaherpesvirinae

Genus Mardivirus

Species Meleagrid alphaherpesvirus 1

Common name Marek’s disease serotype 3 virus

Gallid alphaherpesvirus 2 (Marek’s disease serotype 2 virus)

Taxonomic Unit Classification

Group Group I (dsDNA)

Order Herpesvirales

Family Herpesviridae

Subfamily Alphaherpesvirinae

Genus Mardivirus

Species Gallid alphaherpesvirus 2 (GaHV-2)

Common name Marek’s disease serotype 2 virus

Marek’s disease virus (MDV) causes Marek’s disease in chickens, characterised by asymmetric progressive paresis2 and eventual paralysis of extremities along with nerve enlargements and lymphatic tumours in organs. The disease is responsible for economic loss to poultry industries worldwide (Biggs, 2001). There is no treatment, and a live virus vaccine is considered a preventative measure.

Marek’s disease was first reported in 1907, first isolated in 1967 (Churchill & Biggs, 1967) and vaccine developments followed after. In the early 1970s live non-pathogenic MDV was found to

2 Paresis: muscular weakness caused by nerve damage or weakness.

9 prevent lymphoma formation and since the development of vaccines, the disease has been effectively controlled. All three serotypes of MDV are used as vaccines and live MDV vaccines all induce anti-viral, cell-mediated immunity and antibodies can be detected within 1-2 weeks after infection (Morimura et al. 1997). It has been suggested that various factors can result in the resistance to MDV, including deficiency in lymphocytes, ability of lymphocytes to replicate MDV and cellular antiviral and immune responses. These factors may influence the outcome of the disease and MDV virulence (Lee et al. 1981; Morimura et al. 1997).

MDV vaccines can prevent lymphoma formation without protecting chickens from MDV infection and are therefore considered an anti-tumour, as opposed to anti-viral protection (Morimura et al. 1997).

There are three serotypes that are included in the application which are Marek’s disease serotype viruses 1, 2 and 3. There is evidence to suggest that the anti-tumour mechanisms of the vaccines derived from the serotypes may be different to each other, as monovalent vaccines appear to be the most effective alone but a combination of serotypes increases the protection efficacy against MDV (Morimura et al. 1997).

MDV affects poultry in New Zealand and is a difficult disease to control without vaccination. The FC-126 strain was the first to be registered in New Zealand as a vaccine in 1978 (Table 4) and following this more vaccines with combinations of serotypes were introduced. The vaccine CVI-988 strain has been used in New Zealand since 1994 (both alone and in combination with serotype 3).

In 1988 Marek’s disease was described as potentially the most common and economically important lymphoproliferative disease of domestic poultry and that it has spread throughout New Zealand and the world (Manktelow, 1988). Marek’s disease was identified in 1988 in a broiler flock in New Zealand (Christensen, 1988) and also in 1992 by Howell who suggested that vaccinations are decreasing the prevalence of the disease.

It was indicated that MDV is common in New Zealand poultry (McCausland, 1972; Horner & James, 1975) and that New Zealand is considered to be free from the more virulent strains of MDV. Five live virus vaccines containing MDV have been developed and registered under the ACVM Act.

EPA advice for application APP203705

Registered vaccines in New Zealand Table 4: Registered vaccines for MDV under the ACVM Act. Information taken from the MPI ACVM register.

Name Reg. date Reg. no Company Ingredients Strain Serotype

MD-Vac 09/03/1978 A002733 Pacificvet Ltd HTV3 HTV: FC126 3

VVMD-Vac 31/05/1993 A006751 Pacificvet Ltd MDV, HTV CHV4: 301/B1 2 and 3 HTV: FC126

Nobilis Rismavac + 31/01/1996 A007468 Schering-Plough MDV, HTV CHV: CV1988; 1 CA126 Animal Health Ltd HTV: FC126

Poulvac CVI + HVT 06/05/1999 A007892 Pacificvet Ltd MDV, HVT CHV: CVI988 1 and 3 HVT: FC126

Poulvac Ovaline CVI 17/02/2017 A011274 Pacificvet Ltd MDV CHV: CVI988 1

Eimeria strains (chicken coccidia parasites)

Taxonomic Unit Classification

Phylum Apicomplexa

Class Conoidasida

Order Eucoccidiorida

Family Eimeriidae

Genus Eimeria

Species Eimeria acervulina, E. brunetti, E. necatrix, E. tenella and E. maxima.

Coccidiosis is a disease caused by protozoan parasites of the genus Eimeria. The disease has a huge impact on the poultry industry, as high density housing of birds favours parasite transmission (Blake & Tomley, 2014). Control of coccidiosis in poultry is achieved by drugs and

3 HTV: Herpes turkey virus 4 CHV: Chicken herpes virus

vaccination. Vaccination is used to protect egg-laying, breeder and broiler chickens and most vaccines that are currently available are based on varied formulations of Eimeria live species.

Eimeria only causes coccidiosis in livestock and wild animals, not humans. Eimeria affects a variety of animals including poultry, rabbits, cattle, sheep, goats, pigs, fish and reptiles. In poultry, signs of the disease include intestinal disorders, dehydration, diarrhoea, weight loss and weakness. The infection begins when the host swallows oocysts that excyst and invade cells in the intestine, penetrate the host’s enterocyte and then replicate. Unsporulated oocysts are passed out and these sporulate in the environment where they are passed on to infect another host through ingestion. The earlier endogenous phase of the life cycle is the most important for the induction of protective immune responses. The occurrence of coccidiosis is related to hygiene practices and equipment, presence of rodents and insects and other agents such as viruses and enteric bacteria (Blake & Tomley, 2014; Chapman and Jeffers, 2014; Ahmad et al. 2016).

Coccidiosis due to Eimeria remains a problem within the poultry industry and research is ongoing to try and eliminate or mitigate the effect of this disease. The genomes of all five Eimeria species in this application have been sequenced and are undergoing analysis which contributes invaluable information to the discovery of novel treatments for this disease. Eimeria outbreaks have previously been contained with hygiene practices but new approaches such as vaccinations are used to combat the outbreaks (Ahmad et al. 2016). Five live virus vaccines containing Eimeria have been developed and registered under the ACVM Act.

Vaccinations Live vaccines were studied first, comprising of parasites derived from laboratory or field strains without modification (Williams, 2002). Most commercially available coccidiosis vaccines contain live oocysts of non-attenuated or attenuated strains of different Eimeria species. The first commercial live anticoccidial vaccine, CocciVac® was introduced into the US market in 1952 and contained wild-type strains of E. tenella oocysts. Since the development of that vaccine, reformulations have surfaced since and are widely used in many countries (Ahmed et al. 2016). Despite the success with vaccinations using wild-type strains, immunovariant infections within a flock can lead to the emergence of uncovered strains and ingestion of large numbers of oocysts that increases the risk of disease outbreaks in susceptible animals (Chapman et al. 2002). As a result, it was determined that attenuation of the parasite would overcome that effect.

Live attenuated vaccines consist of parasites of artificially reduced virulence as active ingredients. The only two methods of attenuation that have been used in commercial vaccines are either by passing parasites through embryonated hens’ eggs (vaccines of E. tenella) or by selection for strains that complete their endogenous life cycle faster than wild-type strains that induce immunity without damage to the intestine. The method of selection, commonly known as precocity, was first explored in 1974 and is the most widely used for attenuation of the parasite

EPA advice for application APP203705

in chickens (Jeffers, 1974). These precocious attenuated parasites have reduced virulence and pathogenicity compared to the parent strain.

New Zealand The following list of vaccines provides evidence for Eimeria in New Zealand before and after 29 July, 1998. It is important to note that the application only covers strains within Immucox and Immucox II. The strains of Eimeria in these vaccines were identified as early as 1969 by Pohl (1969).

The first study to recognise Eimeria in New Zealand was carried out at the Department of Animal Health at Massey University and examined birds from poultry farms within New Zealand (Pohl, 1969) and six Eimeria species were found: E. acervulina, E. brunetti, E. maxima, E.mivati, E. necatrix and E. telenna. In 1994, reference to over 20 species of Eimeria were mentioned in the New Zealand Journal of Zoology and considered important within the poultry industry, resulting in economic loss from reduced production (Charleston, 1994). In 1997, coccidiosis was described in the paper ‘Bacterial and parasitic diseases in New Zealand poultry’ - it was mentioned that six pathogenetic Eimeria are present in chickens, and four in turkeys (Black, 1997). Eimeria was recently mentioned in Surveillance magazine (June 2018) as Eimeria was found in five chickens in a small backyard poultry flock in the Matamata-Piako district of the Waikato region (MPI, 2018). Five attenuated live virus vaccines containing Eimeria have been developed and registered under the ACVM Act.

Registered vaccines in New Zealand Table 5: Registered vaccines for coccidiosis in chickens under the ACVM Act (1997). Information taken from the MPI ACVM register.

Name Reg. date Reg. no Company Strains

Immucox (for 02/09/1997 A007156 Pacificvet Ltd E. maxima (live) breeders and layers) E. necatrix (live) E. acervulina (live) E. tenella (live)

Immucox II 11/11/2004 A009383 Pacificvet Ltd E. maxima (live) E. necatrix (live) E. acervulina (live) E. tenella (live) E. brunetti (live)

Paracox 5 26/02/2001 A008106 Schering-Plough E. tenella (attenuated) hp Animal Health Ltd E. mitis (attenuated) hp E. acervulina (attenuated) hp

E. maxima (attenuated) mfp E. maxima (attenuated) cp

Advent 06/05/1999 A007892 Agrihealth NZ Ltd E. tenella fluids E. acervulina fluids E. maxima fluids

Paracox 24/06/1999 A006465 Schering-Plough E. praecox (attenuated) hp Animal Health Ltd E. maxima (attenuated) cp E. brunetti (attenuated) hp E. mitis (attenuated) hp E. tenella (attenuated) hp E. necatrix (attenuated) hp E. acervulina (attenuated) hp E. maxima (attenuated) mfp

Review of information The applicant put forward the argument for these organisms were present in New Zealand prior to the HSNO Act (1996) coming into force in 1998 with a continued presence to modern day. The supporting evidence was presented by highlighting the historical research of development and usage of live attenuated vaccines in New Zealand that contain these organisms.

The definition of live attenuated vaccine according to The Immunisation Advisory Centre of New Zealand5 is:

“Live vaccines are made using ‘wild’ viruses or bacteria that have been attenuated, or weakened, before being included in the vaccine.”

As these live attenuated vaccines contain these organisms and these vaccines have been used for decades in New Zealand, there is evidence to support the presence of these organisms in New Zealand prior to the implementation of the HSNO Act.

All organisms in this application, with the exception of Chicken anaemia virus, have been used in live attenuated vaccines in New Zealand prior to the HSNO Act. In addition, these vaccines are not made by genetic modification.

While live attenuated vaccines of Chicken anaemia virus were not introduced in New Zealand until just after the HSNO Act came into force in 1998, the evidence from scientific literature suggests that this virus has been present in New Zealand for a lengthy period of time. The earliest report of this virus was in 1991 and subsequent reports were made in 1992 through

5 The Immunisation Advisory Centre of New Zealand: Types of vaccines: Accessed on 15 November 2018. http://www.immune.org.nz/vaccines/vaccine-development/types-vaccines

EPA advice for application APP203705

isolations from bone marrow and, in another report, CAV DNA were isolated from infected chicks. A 2013 report by Watts identified CAV as a common disease of chicken flocks (see paragraph 11).

Conclusion After completing our assessment of the information that was submitted by the applicant, we consider that Tremovirus A (Avian encephalomyelitis virus), Chicken anaemia virus (CAV or CIAV), Fowlpox virus, Gallid alphaherpesvirus 2 (Marek’s disease serotype 1 virus), Gallid alphaherpesvirus 2 (Marek’s disease serotype 2 virus), Maleagrid alphaherpesvirus 1 (Marek’s disease serotype 3 virus), Eimeria acervulina, E. brunetti, E. necatrix, E. tenella and E. maxima are present in New Zealand and have been present for a significant period of time (i.e. immediately before 29 July 1998) based on the evidence presented.

Recommendation Our assessment has found that there is sufficient evidence to show that Tremovirus A (Avian encephalomyelitis virus), Chicken anaemia virus (CAV or CIAV), Fowlpox virus, Gallid alphaherpesvirus 2 (Marek’s disease serotype 1 virus), Gallid alphaherpesvirus 2 (Marek’s disease serotype 2 virus), Maleagrid alphaherpesvirus 1 (Marek’s disease serotype 3 virus), Eimeria acervulina, E. brunetti, E. necatrix, E. tenella and E. maxima should be determined as not new for the purpose of the Act.

Appendix 1: Correspondence with ACVM

Hey

See answers below. Just so you know for future reference, the ACVM list of registered products should only have currently registered products on it.

Cheers

BVSc | Senior Adviser Veterinary Medicines, ACVM Programmes & Appraisals

From: [mailto: @epa.govt.nz] Sent: Monday, 14 January 2019 9:46 AM To: < @mpi.govt.nz> Subject: Request on veterinary medicine products

Hi ,

We are in need of ACVM assistance on one of our applications and I thought I would contact you in relation to a statutory determination application that I am working on for a handful of poultry vaccines.

As this is a statutory determination to determine whether or not these organisms are present in New Zealand, we do not generally seek ACVM expertise. However, in this instance, we would like to enquire if the following poultry vaccines are currently registered under the ACVM Act.

A001515 - AE-Vac currently registered

A004361 – AE-Poxine currently registered

A009132 – AviPro Thymovac currently registered

A011331 – Cux-1. Circomune currently registered

A002733 – Chick-N-Pox currently registered

A002780 – Poxine (I think the applicant got the registration code wrong and it’s actually A002779) currently registered

A011274 – Poulvac Ovoline CVI currently registered

A007892 – POULVAC CVI+HVT currently registered

A002733 – MD-Vac currently registered

A006751 – VVMD-Vac currently registered

EPA advice for application APP203705

A005943 - Poulvac Marek CVI (I couldn’t find any products that match this registration code nor name) – no longer registered.

I found most of these products on the ACVM register (Eatsafe website) but I’m unsure if they have expired or not as the register does not show this information (I’m assuming they are registered). Please can you or another assessor from ACVM have a look for us. https://eatsafe.nzfsa.govt.nz/web/public/acvm-register

If you or another ACVM assessor could let me know by the end of next week that would be greatly appreciated.

Advisor - New Organisms | Level 10, 215 Lambton Quay, Wellington 6140, New Zealand

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References

Ahmad, T.A., El-Sayed, B.A. and El-Sayed, L.H. 2016. Development of immunisation trials against Eimeria spp. Trials in Vaccinology. 5: 38-47. Biggs, P.M. 2001. The history and biology of Marek’s disease virus. Marek’s Disease. Current topics in Microbiology and Immunology. 255: 1-24. Biggs, P.M. 2001. Pathogenesis of Marek’s disease virus infection. Marek’s Disease. 25-55. Black, A. 1997. Bacterial and parasitic diseases in New Zealand poultry. Surveillance. 24(4): 4. Blake, D.P. and Tomley, F.M. 2014. Securing poultry production from the ever-present Eimeria challenge. Trends in Parasitology. 30(1): 12-19. Calnek, B.W., Taylor, P.J. and Sevion, M., 1961. Studies on avian encephalomyelitis. Virus Development and application of an oral vaccine, Avian diseases. 5: 297-312. Chapman, H.D., Cherry, T.E., Danforth, H.D., Richards, G., Shirley, M.W. and Williams, R.B. 2002. Sustainable coccidiosis control in poultry production: the role of live vaccines. International Journal for Parasitology. 32: 617-629. Chapman, H.D. and Jeffers, T.K. 2014. Vaccination of chickens against coccidiosis ameliorates drug resistance in commercial poultry production. International Journal for Parasitology: Drug and Drug Resistance. 4: 214-217. Charleston, W.A.G. 1994. Toxoplasma and other protozoan infections of economic importance in New Zealand. New Zealand Journal of Zoology. 21: 67-81. Christensen, N.H. 1988. A study of the effects of Marek’s disease in a broiler flock. New Zealand Veterinary Journal. 36(2): 82-85. Churchill, A.E. and Biggs, P.M. 1967. Agent of Marek’s disease in tissue culture. Nature. 215: 528- 530. Gartrell, B.D., Stone, M., King, C. and Wang, J. 2003. An outbreak of disease caused by psittacinepoxvirus in rosellas. Surveillance. 30(3): 11-13. Horner, G.W. and James, M.P. 1975. Isolation of Marek’s disease virus from affected chickens. New Zealand Veterinary Journal. 20(9): 160-166. Howell, L.J. 1992. Viral diseases and the New Zealand Poultry Industry. Surveillance. 19(2): 15-17. Howell, L.J. and Bell, C.W. 1987. Avian encephalomyelitis virus antibodies in New Zealand chicken flocks. New Zealand Veterinary Journal. 35(9): 157-159. Hye Jeong, H., Howe, L., Alley, M. and Gartrell, B. 2011. The phylogenetic analysis of avipoxvirus in New Zealand. Veterinary Microbiology. 150: 80-87. International Committee on Taxonomy of Viruses (ICTV): Accessed 14 November 2018 at: talk.ictvonline.org/taxonomy/ Jeffers, T.K. 1974. Attentuation of Eimeria tenella through selection for precociousness. Journal of Parasitology. 61(6): 1083-1090. Jones, E.E. 1932. An encephalomyelitis in the chicken. Science. 76: 331-332. Lee, L.F., Powell, P.C., Rennie, M., Ross, L.J. and Payne, L.N. 1981. Nature of genetic resistance to Marek’s disease in chickens. Journal of National Cancer Institute. 66(4): 789-796. MacDiarmid, S.C. 1991. The importation into New Zealand of meat and meat products: a review of the risks to animal health. Ministry for Agriculture and Forestry. 177-179. McCausland, I.P. 1972. Diseases of the domestic fowl in northern New Zealand. New Zealand Veterinary Journal. 23(6): 102-104. Manktelow, B.W., Lohr, J.E., Wilks, C.R. and Christensen, N.H. 1988. Avian Encephalomyelitis. Avian Veterinary Handbook. 120: 75. Mayr, A. and Danner, K. 1976. Oral immunisation against pox: Studies on fowlpox as a model. Developments in Biological Standardisation. 33: 249-259. Ministry for Primary Industries (MPI): 2018 Quarterly Report of Diagnostic Cases: January to March 2018. Surveillance. Ministry for Primary Industries. 45(2) Ministry for Primary Industries (MPI): Veterinary Medicines from ACVM Register cited: AE-Vac (A001515), AE-Poxine (A004361), Nobilis AE + POX (A006061), AviPro Thymovac (A009132), Cicomune (A011331), Immucox (A007156), Immucox II (A009383), Paracox 5 (A008106), Advent (A007892) and Paracox (A006465). Registrations were accessed on MPI’s ACVM register between 12-16 November 2018 at: https://eatsafe.nzfsa.govt.nz/web/public/acvm-register

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Morimura, T., Ohashi, K., Sugimoto, C. and Onuma, M. 1997. Pathogenesis of Marek’s disease (MD) and possible mechanisms of immunity induced by MD vaccine. Journal of Veterinary Medical Science. 60(1): 1-8. Pattison, M., McMullin, P., Bradbury, J. and Alexander, D. 2008. Poultry diseases. 6: 398-401. Pohl, R. 1969. Coccidiosis of the fowl in New Zealand. New Zealand Veterinary Journal. 17(12): 249- 250. Schaaf, K. and Lamoreux, W. 1955. Control of avian encephalomyelitis by vaccination. American Journal of Veterinary Research. 16(61 part 1): 627. Stanislawek, W.L. and Howell, J. 1994. Isolation of chicken anaemia virus from broiler chickens in New Zealand. New Zealand Veterinary Journal. 42(2): 58-62. Tham, K.M. and Stanislawek, W.L. 1992. Polymerase chain reaction amplification for direct detection of chicken anaemia virus DNA in tissues and sera. Avian diseases. 36: 1000-1006. Tripathy, D.N. and Reed, W.M. 2013. Diseases of Poultry. 11th Ed. 253-269. Watts, J. 2013. Diseases of backyard poultry in New Zealand. Surveillance. 40(1): 1-13. Williams, R. 2002. Anticoccidial vaccines for broiler chickens; pathways to success. Avian Pathology. 31: 317-353. Yuasa, N., Taniguchi, T. and Yoshida, I. 1979. Isolation and some characteristics of an agent including anaemia in chicks. Avian diseases. 23: 366-385.

Appendix 2: s26 pathway Decision pathway for applications under Section 26 for determination as to whether an organism is a new organism

Context

This decision pathway describes the decision-making process for applications under Section 26 for determination as to whether an organism is a new organism.

Introduction

The purpose of this decision pathway is to provide the HSNO decision maker6 with guidance so that all relevant matters in the Hazardous Substances and New Organisms Act (1996) (the Act) and the Hazardous Substances and New Organisms (Organisms Not Genetically Modified) Regulations (1998) (the Regulations) have been addressed. It does not attempt to direct the weighting that the HSNO decision maker may decide to make on individual aspects of an application.

The decision pathway has two parts –

 Flowchart (a logic diagram showing the process prescribed in the HSNO Act and the Methodology to be followed in making a decision), and  Explanatory notes (a discussion of each step of the process).

Of necessity the words in the boxes in the flowchart are brief, and key words are used to summarise the activity required. The explanatory notes provide a description of each of the numbered items in the flowchart, and describe the processes that should be followed.

For proper interpretation of the decision pathway it is important to work through the flowchart in conjunction with the explanatory notes.

6 The HSNO decision maker refers to either the EPA Board or any committee or persons with delegated authority from the Board.

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Figure 17 Explanatory Notes

Section 26 pathway A

Item 1 Review the content of the application and all relevant information Review the application, staff advice and any relevant information held by other Agencies, and advice from experts.

Item 2 Is further information required? Review the information and determine whether or not there is sufficient information available to make a decision.

Item 3 Seek additional information (Section 52 and Section 58) If the HSNO decision maker considers that further information is required, then this may be sought either from the applicant (if there is an external applicant) or from other sources. If the HSNO decision maker considers that the information may not be complete but that no additional information is currently available, then the HSNO decision maker may proceed to make a determination. If the application is not approved on the basis of lack of information (or if the organism is considered new) and further information becomes available at a later time, then the HSNO decision maker may choose to revisit this determination.

Item 4 Is it an organism (i.e. fits the “organism” definition in Section 2)? An organism

(a) does not include a human being: (ab) includes a human cell: (b) includes a micro-organism: (c) includes a genetic structure, other than a human cell, that is capable of replicating itself, whether that structure comprises all or only part of an entity, and whether it comprises all or only part of the total genetic structure of an entity: (d) includes an entity (other than a human being) declared to be an organism for the purposes of the Biosecurity Act 1993: (e) includes a reproductive cell or developmental stage of an organism

If yes, go to item 5. If no, as this is not an organism, it is not regulated under the new organism provisions of the HSNO Act.

Item 5 Is the determination about a potential GMO (Section 2A(1)(d))? If the determination relates to whether an organism is a potential GMO, go to pathway B. If the organism is not a GMO, go to item 6.

Item 6 Does the organism belong to a species that was known to be present in NZ immediately before 29 July 1998 (Section 2A(1)(a))? Determine on the basis of the available information whether on balance of probabilities the organism is known to belong to a species that was present in New Zealand immediately prior to 29 July 1998. For the purposes of making a Section 26 determination an organism is considered to be present in New Zealand if it can be established that the organism was in New Zealand: (a) immediately before 29 July 1998; and

(b) not in contravention of the Animals Act 1967 or the Plants Act 1970 (excluding rabbit haemorrhagic disease virus, or rabbit calicivirus). If yes, go to item 7 to test the organism against the next criterion. If no, go to item 12.

Item 7 Is the organism prescribed as a risk species and was not present in New Zealand at the time of promulgation of the relevant regulation (Section 2A(1)(b))? Determine whether the organism belongs to a species, subspecies, infrasubspecies, variety, strain, or cultivar that has been prescribed as a risk species by regulation established under Section 140(1)(h) of the Act. If the organism is prescribed as a risk species, determine whether it was present in New Zealand when it was prescribed. The organism is a new organism if it was not present in New Zealand at the time of the promulgation of the relevant regulation. Note: at this point it may become apparent that the organism is an unwanted organism under the Biosecurity Act. If this is the case, then MPI and DOC may be advised (they may already have been consulted under items 1, 2 and 3). If yes, go 12. If no, go to item 8 to test the organism against the next criterion.

Item 8 Has a containment approval been given for the organism under the Act (Section 2A(1)(c))? For the purposes of making a Section 26 determination, this will also include the following organisms which are “deemed” to be new organisms with containment approvals under the HSNO Act: (a) animals lawfully imported under the Animals Act 1967 before 29 July 1998 pursuant to Section 254 of the HSNO Act; (b) animals lawfully present in New Zealand in a place that was registered as a zoo or circus under the Zoological Garden Regulations 1977 pursuant to Section 255 of the HSNO Act (except where other organisms of the same taxonomic classification were lawfully present outside of a zoo or circus –see section 2A(2)(c)); (c) hamsters lawfully imported under the Hamster Importation and Control Regulations 1972 pursuant to Section 256 of the HSNO Act; or (d) plants lawfully imported under the Plants Act 1970 before 29 July 1998 pursuant to Section 258 of the HSNO Act. If yes, go to item 12. If no, go to item 9 to test the organism against the next criterion.

Item 9 Has a conditional release approval been given for the organism (Section 2A(1)(ca))?

If yes, go to item 12. If no, go to item 10 to test the organism against the next criterion.

Item 10 Has a qualifying organism with controls approval been given for the organism (Section 2A(1)(cb))? A “qualifying organism” is an organism that is or is contained in a “qualifying medicine” or “qualifying veterinary medicine”. These terms are defined in Section 2 of the HSNO Act. If yes, go to item 12. If no, go to item 11 to test the organism against the next criterion.

Item 11 Is the organism known to have been previously eradicated (Section 2A(1)(e))?

EPA advice for application APP203705

Determine whether the organism belongs to a species, subspecies, infrasubspecies, variety, strain, or cultivar that is known to have been previously eradicated. Eradication does not include extinction by natural means but is considered to be the result of a deliberate act. If yes, go to item 12. If no, then the organism is not a new organism.

Item 12 Has HSNO release approval without controls been given for an organism of the same taxonomic classification under Sections 35, 38 or 38I of the Act or has an organism of the same taxonomic classification been prescribed as a not new organism (Section 2A(2)(a))? If a release approval has been given for an organism of the same taxonomic classification under Section 35 or 38 of the Act then the organism is not a new organism. If a release approval has been given for an organism of the same taxonomic classification under Section 38I of the Act without controls then the organism is not a new organism, however, if this approval has been given with controls then it is a new organism. If an organism of the same taxonomic classification has been prescribed by regulations as not a new organism7 then it is not a new organism. If yes, the organism is not a new organism. If no, the organism is a new organism.

7 http://www.legislation.govt.nz/regulation/public/2009/0143/latest/whole.html#DLM2011201

Section 26 pathway B

Item 1 Have the genes or other genetic material been modified by in vitro techniques or inherited from genes or other genetic material that has been modified by in vitro techniques? If yes, go to item 2. If no, the organism is not a genetically modified organism. However, you must check whether it meets the other new organism criteria so go to Pathway A item 6 onwards.

Item 2 Does the organism result solely from selection or natural regeneration, hand pollination, or other managed, controlled pollination (Regulation 3(1)(a) of the Regulations)? Is the organisms solely the result of selection or natural regeneration, hand pollination, or other managed, controlled pollination? If yes, the organism is not a GMO. However, you must check whether it meets the other new organism criteria so go to Pathway A item 6 onwards. If no, go to item 3.

Item 3 Is the organism regenerated from organs, tissues, or cell culture (Regulation 3(1)(b) of the Regulations)? Is the organism regenerated from organs, tissues, or cell culture, using any of the following techniques: selection and propagation of somaclonal variants, embryo rescue, and cell fusion (including protoplast fusion)? If yes, the organism is not a GMO. However, you must check whether it meets the other new organism criteria so go to Pathway A item 6 onwards. If no, go to item 4.

Item 4 Is the organism a result of mutagenesis treatments in use on or before 29 July 1998 (Regulation 3(1)(ba) of the Regulations)? Is the organisms the result of mutagenesis that uses a chemical or radiation treatment that was in use on or before 29 July 1998? If yes, the organism is not a GMO. However, you must check whether it meets the other new organism criteria so go to Pathway A item 6 onwards. If no, go to item 5.

Item 5 Does the organism result solely from artificial insemination techniques (Regulation 3(1)(c) of the Regulations)? Is the organism solely the result of artificial insemination, superovulation, embryo transfer, or embryo splitting? If yes, the organism is not a GMO. However, you must check whether it meets the other new organism criteria so go to Pathway A item 6 onwards. If no, go to item 6.

Item 6 Does the organism result from spontaneous deletions, rearrangements or amplifications (Regulation 3(1)(e) of the Regulations)? Is the organism a result of spontaneous deletions, rearrangements, and amplifications within a single genome, including its extrachromosomal elements? If yes, the organism is not a GMO. However, you must check whether it meets the other new organism criteria so go to Pathway A item 6 onwards. If no, go to item 7.

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Item 7 Is the organism modified solely by the movement of nucleic acids using physiological processes, plasmid loss or spontaneous deletion (Regulation 3(1)(d) of the Regulations)? Is the organism modified solely by the movement of nucleic acids using physiological processes, including conjugation, transduction, and transformation, or by plasmid loss or spontaneous deletion? If yes, go to item 8. If no, go to item 9.

Item 8 Does the organism contain nucleic acid molecules produced using in vitro manipulation transferred using physiological processes, plasmid loss or spontaneous deletion (Regulation 3(2) of the Regulations)? Are nucleic acid molecules produced using in vitro manipulation transferred using any of the techniques referred to in item 7? If yes, go to item 9. If no, the organism is not a GMO. However, you must check whether it meets the other new organism criteria so go to Pathway A item 6 onwards.

Item 9 Has HSNO release approval without controls been given or has an organism of the same taxonomic classification with the same genetic modification been prescribed as a not new organism (Section 2A(2)(b))? If a release approval has been given for an organism of the same taxonomic classification with the same genetic modification under Section 38 of the HSNO Act then the organism is not a new organism. If a release approval has been given for an organism of the same taxonomic classification with the same genetic modification under section 38I of the HSNO Act without controls then the organism is not a new organism, however, if this approval has been given with controls then it is a new organism. If an organism of the same taxonomic classification with the same genetic modification has been prescribed by regulations as not a new organism8 then it is not a new organism. If yes, the organism is not a new organism. If no, the organism is a new organism.

8 http://www.legislation.govt.nz/regulation/public/2009/0143/latest/whole.html#DLM2011201