PHARMACOVIGILANCE/POST ILLOILO;;;;;;;;;;;;;;;;;;;;;;;;; ` MARKETING SURVEILLANCE NEWSLETTER

VOL. 13 No.3 2020

EDITOR’S NOTE... PHARMACOVIGILANCE: A We wish to thank all our numerous stakeholders who have been working tirelessly with the National VIEW ON MEDICAL Pharmacovigilance Centre (NPC) to ensure the safe use of medicines in Nigeria. The NPC is committed to DEVICES sending out the quarterly newsletter to its stakeholders. The objectives of the Newsletter are to disseminate information on Pharmacovigilance

activities nationally and globally, to educate stakeholders on medicine safety issues, to promote Content rational use of drugs and to promote reporting of Adverse Drugs Reactions (ADRs). This edition of the newsletter focuses on Pharmacovigilance: A view on

Med Safety Application medical devices We encourage Health care Professionals and other Pharmacovigilance: A View on stakeholders to continue to report all adverse drug

Medical Devices reactions. Your valued comments and acknowledgement of receipt of this issue through our NAFDAC Pharmacovigilance Focal email addresses ([email protected]; Persons for States [email protected], [email protected]) would be most appreciated.

Guide to Nigeria NPC Adverse Drug You may also send us an email if there are any areas of Reaction (ADR) Electronic Reporting interest that you would want addressed in subsequent issues of the newsletter (e-Reporting) System Thank you for your relentless efforts in strengthening Pharmacovigilance System in Nigeria.

Fraden Birtus fsi

National Coordinator, National Pharmacovigilance Centre (NPC), National Agency for Food and Drug Administration and Control (NAFDAC) Plot 2032 Olusegun Obasanjo Way, Wuse Zone 7, Abuja, Nigeria. PMB 5032 Wuse Abuja. Telephone: 08036047233 E-mail: [email protected], [email protected], [email protected]. Web site: www.nafdac.gov.ng

Text any DRUG RELATED PROBLEM to the SHORT CODE 20543 (For free on MTN, Glo, Etisalat and Airtel) for action by the Pharmacovigilance Centre

Pharmacovigilance/Post Marketing Surveillance Newsletter VOL. 13 No.3 2020

MED SAFETY The Agency related to the systems and structures that are APPLICATION has adopted required for pre and post – authorization the Med monitoring of safety and effectiveness of health Safety App (WEB-RADR) for improved ADR products in Nigeria. The goal of the policy is to reporting in Nigeria. provide a strategic framework for the entrenchment of pharmacovigilance into the The Med Safety App was developed through the healthcare system in Nigeria to ensure overall Innovative Medicines Initiative WEB-RADR safety in the use of medicines and other related project sponsored by the WHO, WHO products. Hence the Scope of Products for Programme for International Drug Monitoring Pharmacovigilance Regulatory System in Nigeria (UMC) and Medicines and HealthCare Products is not limited to medicines but includes other Regulatory Agency (MHRA, UK). related products such as vaccines/ biologics, The app was first piloted and made available in medical devices, cosmetics, chemicals and the UK, Netherlands and Croatia. The app was herbals. subsequently rolled out in Burkina Faso and Medical Devices Zambia with WHO support. The Med Safety app The WHO defines a Medical Device as any has been launched successfully in Armenia, instrument, apparatus, implement, machine, Ethiopia, Cote d’Ivoire, Tanzania and Ghana. appliance, implant, reagent for in vitro use, Med Safety App offers a low-cost approach for software, material or other similar or related National Medicines Regulatory Authorities to: article, intended by the manufacturer to be used, alone or in combination, for human • collect, view and review ADR data beings, for one or more of the specific medical submitted and directly linked to Vigiflow purpose(s) of: platform • diagnosis, prevention, monitoring, • deliver safety messages, DHCPs, alerts, treatment or alleviation of disease, notices etc. to MAHs, HCPs and other stakeholders • diagnosis, monitoring, treatment, alleviation of or compensation for an Healthcare professionals and the general public injury, please note that the App was launched on 4th September, 2020 and is available for download • investigation, replacement, on Android and IOS on stores. modification, or support of the anatomy or of a physiological process,

PHARMACOVIGILANCE: A VIEW ON MEDICAL • supporting or sustaining life, DEVICES • control of conception,

• disinfection of medical devices The Nigerian National Pharmacovigilance Policy • providing information by means of in The Nigerian National Pharmacovigilance Policy vitro examination of specimens derived which was launched in 2013 addresses issues from the human body;

2 | P a g e

Pharmacovigilance/Post Marketing Surveillance Newsletter VOL. 13 No.3 2020

and does not achieve its primary intended action • is an active medical device; by pharmacological, immunological or • delivers medicinal products, energy or metabolic means, in or on the human body, but radiation; which may be assisted in its intended function i by such means. • could modify blood or other body fluids;

Regulation of medical devices • is used in combination with another medical In Nigeria, the National Agency for Food and deviceiii Drug Administration and Control has the responsibility of ensuring that Medical Devices NAFDAC has adapted the international placed on the Nigerian market for use meet the classification for regulation of medical devices in requirements for Quality, Safety and Efficacy Nigeria as shown in table 1. Below throughout the lifecycle of the product. The Act International Examples Risk Level empowering NAFDAC for this role interprets a Classification medical device as any instrument, apparatus or A Cholesterol, uric acid test system; Low contrivance (including components, parts and Surgical Instrument; Bandage, accessories thereof) manufactured, sold or Surgical camera; Electric operating advertised for internal or external use in the table, Patient scale diagnosis, treatment, mitigation or prevention of any disease, disorder, abnormal physical state B Pregnancy self-testing, Electric Low – Hospital Bed, Surgical Lamp, Moderate or the symptom thereof, in man or in animal ii. Surgical Mask

To ensure proper regulation and safety C Blood glucose self-testing, ECG, X- Moderate - monitoring of medical devices the Global ray Unit, Syringe, Condom, Contact High Harmonization Task Force (GHTF) has prepared lens guidance document with set of rules which D HIV Blood donor screening, Stent, High assist to allocate medical device to one of four Intraocular lens (IOL), Defibrillator, classes using a set of classification rules which Pacemaker take account of the hazard presented by a particular device. The hazard presented by a particular medical device depends substantially It generally follows that regulatory control of on its intended use and the technology it utilises. medical devices by National Regulatory Consequently, the classification rules stipulated Authorities such as NAFDAC increases with in the guidance document take factors into increasing hazard or risk level of the medical account such as, whether the device: device; more stringent regulations and monitoring apply to class D medical devices • is life supporting or sustaining; which are associated with the highest risk. • is invasive and if so, to what extent and for how long;

• incorporates medicinal products, or human/animal tissues/cells;

3 | P a g e

Pharmacovigilance/Post Marketing Surveillance Newsletter VOL. 13 No.3 2020

Post Marketing Authorization Safety reporting platform and more recently, the med Monitoring of Medical Devices safety app which is publicly available on android Two main approaches are employed in the Post and IOS stores. approval monitoring of devices: Passive and In active surveillance or pharmacovigilance, Active surveillance or pharmacovigilance. active measures are taken to detect and report Passive surveillance involves submitting of adverse effects/events. Such as active follow-up spontaneous adverse events reports with use of of patients and recording of all medical events. devices to the NPC, by manufacturers or Follow-up may be done prospectively or Marketing Authorisation Holders (MAHs), retrospectively. There are 2 kinds of active post- Healthcare professionals, and consumers. The approval surveillance for medical devices: NPC will then collate the information and conduct of prospective organized clinical studies determine if an intervention is needed. and organization of active medical product registries capable of generating device safety Reports to be submitted may include issues of and performance datav malfunctions, injuries, or fatalities associated with the use of Medical Devices. Such reporting NAFDAC, NPC is working towards a more active is voluntary for the reporting health approach for safety monitoring of professionals or healthcare providers working in pharmaceutical products by way of Smart Safety establishments other than the manufacturing or Surveillance (SSS) initiative. SSS is a risk-based importing/distributing companies. It is a approach towards pharmacovigilance especially professional ethical obligation. around the introduction of new medicines to treat priority diseases. It is however mandatory for all Marketing Authorization Holders (MAHs) and Benefits of Safety Monitoring of Medical manufacturers of medical devices to report to devices the NPC when they become aware of The primary aim of post marketing Safety information that reasonably suggests that one Monitoring of medical devices is to improve the of their marketed devices may have caused or health and safety of patients or users and health contributed to a death or serious injury or has care professionals by reducing the likelihood of malfunctioned and the malfunction of the reoccurrence of adverse events. Adverse event device or a similar device that they market reporting is necessary to monitor medical device would be likely to cause or contribute to a death use and their performance in the real world and or serious injury if the malfunction were to detect trends that may indicate emerging safety recur.iv The MAHs and Manufacturers are to and performance issues. These activities will report such events occurring in Nigeria or guide NAFDAC to take appropriate regulatory anywhere in the world. action to address the issues, thereby reducing the impact on the public. The NPC has deployed several channels for spontaneous reporting of adverse events to A well-completed adverse drug reaction medicines and other pharmaceutical products reporting form submitted could result in one or such as the use of the yellow forms, the e- more of the following:

4 | P a g e

Pharmacovigilance/Post Marketing Surveillance Newsletter VOL. 13 No.3 2020

• Answer questions about the • Other regulatory interventions as the performance of certain devices situation may warrant including • Additional investigations into the use of corrective action for the device or the device in Nigeria. withdrawal • Educational initiatives to improve the All these translate to improvement on the safe use of the devices quality of care offered to patients, hence, • Changes in the labelling or Instructions for use of the devices to make them improved patient confidence in professional safer. practice and consequently professional growth • Reclassification of rescheduling of Table 2. shows some Regulatory Decisions Taken medical devices as a Result of Pharmacovigilance

S/N Drug Reasons for action taken Regulatory Decision taken Year action was taken

1. Tramadol Irrational use and increased Reclassification of drug from 2012 reports of ADRs POM to controlled drug

2. ISOTAB Contamination of product Targeted alert notice to HCP 2012 posted on Agency’s website and NPC’s newsletter

3. Gatifloxin Risk of serious Ban of product and withdrawal 2012 hyperglycaemia and of all brands from hypoglycaemia hypoglycaemia

4. Infusion fluid Contaminated infusion Mop up of affected batches, 2011 manufacturers GMP reevaluated, intervention in storage

5. Prevanar 13 AEFI reports of death from Company directed to carry out 2011 Prevenar 7 and insufficient phase IV study to ascertain evidence of efficacy and safety and efficacy in the safety of prevenar 13 in reduction of pneumococcal Nigeria strains that are prevalent in Nigeria and the compatibility of vaccine with the vaccines used in routine immunization in Nigeria

5 | P a g e

Pharmacovigilance/Post Marketing Surveillance Newsletter VOL. 13 No.3 2020

6. Rosiglitazone Risk of congestive heart Recommendation for voluntary 2011 failure withdrawal by MAH

7 Chlorzoxazone Suspected hepatotoxicity Dear Doctor letter to actively 2010 monitor the safety of the use of chlorzoxazone with regards to its potential to precipitate hepatotoxicity

8 Formalin Public misuse as an Reclassification from a general 2010 abortifacient chemical to a restricted chemical

9 Codeine Public misuse Public enlightenment 2010 containing cough mixtures

10 Gentamicin Increased risk of ototoxicity Recall/mop of gentamicin 2010 280mg/2ml and nephrotoxicity and 280/2ml from circulation increased risk of endotoxin reactions

11 Teething Low benefit/risk ratio Banned in Nigeria 2009 mixture

12 Abacavir Serious hypersensitivity Review of core safety 2008 reaction information by GSK to include (Ziagen®) HLAB*5701 gene testing

Challenges Medical Devices: lists the challenges of A review of individual case safety report (ICSRs) monitoring and assessing the safety of medical database at the Nigerian National devices post marketing authorization. Some of Pharmacovigilance Centre (NPC) reveals that the these challenges apply to safety monitoring of Centre has not received any report of adverse medical devices in Nigeria and include events associated with the use Medical devices • Adverse events related to medical from 2004 to August 2020. devices are widely under-reported. Even The U.S. Food and Drug Administration’s Center when a problem is detected, under- for Devices and Radiological Health (CDRH) in a reporting makes it difficult to assess the report titled “Ensuring the Safety of Marketed true public health risk.

6 | P a g e

Pharmacovigilance/Post Marketing Surveillance Newsletter VOL. 13 No.3 2020

• Health-care providers generally don’t III devices pose the highest risk. Device document device use in patient records, classification by the US FDA also depends on making it difficult to identify the specific the intended use of the device and device involved when an adverse event its indications for usevii. occurs. A report on medical device reporting to the US • Medical devices lack unique identifiers FDA show that of about 4000 types of medical and manufacturers continually produce devices tracked by the institution, only 6 of modified versions of their products. those device types account for about 25% of the • Devices are often used off-label, reports of adverse events (device injury) meaning they are used for indications between 2008 to 2017. Table 3. Show device and patient populations not included in type most frequently reported on to the US FDA the product’s pre-market testing and between 2008 to 2017 approval. Device type Class Number of • Medical devices are not just being used reports in hospitals and clinics but in patients’ Hip prosthesis II 103,104 homes, which means more non- professionals are involved. This adds an Insulin pump with II 94,826 element of uncertainty in diagnosing the senser cause of a problem and identifying Spinal Stimulator II/III 78,172 possible solutions. vi Surgical Mesh II 60,795 Pharmacovigilance of medical devices on the Insulin pump II 60561 international scene implanted Regulatory Agencies around the world monitor the safety of medical devices to contribute to a Defibrillator II/III 59,457 better understanding of their possible adverse effects when they are used in real time outside Hip prosthesis is the device type with the highest of pre-marketing assessments. number of reports (103,104) of adverse events/ injuries.viii The FDA highlights possible events In the United States, the Center for Devices & that may occur after hip implant surgery, Radiological Health (CDRH) of the Food & Drug regardless of the type of hip system implanted, Administration (FDA) is specifically responsible as follows: for medical devices regulation. The FDA CDRH • Hip dislocation, when the ball of the categorizes medical devices into one of three thighbone (femur) slips out of its socket classes as Class I, II, or III based on their potential in the hip bone (pelvis) risks and the regulatory controls necessary to • Bone fracture provide a reasonable assurance of safety and • Joint infection effectiveness. Class I devices generally pose the • Local nerve damage with numbness or weakness lowest risk to the patient and/or user and Class • Device loosening or breakage

7 | P a g e

Pharmacovigilance/Post Marketing Surveillance Newsletter VOL. 13 No.3 2020

• Difference in leg lengths NAFDAC implores healthcare providers to be • Bone loss (osteolysis) relentless in the spontaneous reporting of • Various types of local or systemic Adverse events to pharmaceutical products that reactions to particles or ions generated occur during their practice. This is a professional from the use of the implant ethical obligation of the healthcare provider. Patients who have hip implants may observe The various reporting platforms deployed by symptoms that may occur three or more months NAFDAC: the ADR reporting forms, e-reporting after surgery that may indicate that their device platform and the med safety app can be used in is not functioning properly. These include: sending individual case safety reports to the • Pain in the groin, hip or leg NPC. • Swelling at or near the hip joint • A limp or change in walking ability Reports of adverse events to pharmaceutical • Noise (popping, grinding, clicking or products submitted to NAFDAC are treated with squeaking) from the hip jointix a high level of confidentiality and are used with a sole purpose of improving the healthcare A retrospective study done in Colombia system. It is important to note that the reporting describing reports of adverse events or incidents of an adverse event does not make the MAH, related to medical devices between 2014 and healthcare professionals, patients or user 2017 showed that the devices that were most liability for the event or its consequences. frequently reported as having events or adverse incidents were those belonging to the vascular access category, with 45.2% of cases, followed by surgical equipment, with 20.2%. The causes NAFDAC PHARMACOVIGILANCE of the events or adverse incidents were most FOCAL PERSONS FOR STATES often failures of the mechanical components, at 50.6%, followed by manufacturing defects, at In a bid to strengthen pharmacovigilance x 28.7%. activities in all the 36 states of the Federation and the FCT, the Agency has assigned staff in Conclusion each NAFDAC state office to be the focal persons There is much work to be done in strengthening for pharmacovigilance activities for the states. pharmacovigilance systems in Nigeria. The The focal persons have the responsibility of responsibility rests on all stakeholders: coordinating pharmacovigilance activities in the Government (e.g., Ministry of Health, states, with roles such as: Regulatory body, PHP), Marketing Authorization Holders, distributors, healthcare professionals, • Disseminating and retrieval of ADR forms public health programs, patients and the general • Pharmacovigilance advocacy public. Some stakeholders have mandatory roles • Pharmacovigilance investigations and others voluntary roles, both must be The Focal persons will liaise with the healthcare performed for results to be achieved. professionals, consumers and other stakeholders in the states and ensure that all

8 | P a g e

Pharmacovigilance/Post Marketing Surveillance Newsletter VOL. 13 No.3 2020

ADRs generated reach the National ➢ It is important to report the following Pharmacovigilance Centre (NPC) promptly. very important details even if they are not tagged as mandatory field (*); You may request the contact details of the focal  Manufacturer of medicine persons for your state by sending us an email Probably causing the reaction, through [email protected]  Strength (as stated on medicine packet) GUIDE TO NIGERIA NPC ADVERSE  Dosage (as taken) DRUG REACTION (ADR) ELECTRONIC  Route (as administered or taken) REPORTING (E-REPORTING) SYSTEM  Place where medicine was obtained, The Nigeria NPC has deployed e-Reporting of  End date of medication or ADRs. You may access this through the NAFDAC duration of use of the medicine, website: https://www.nafdac.gov.ng/  Reason for taking the medicine  What else did you do (Action click on Pharmacovigilance & Post Market taken with medicine) Surveillance link under Services. (bottom-left of  Has the medicine caused a similar the home page) reaction before? Select NAFDAC ADR e-Reporting Form under ➢ You can add as many medicines as useful resources (right side of the page). possible by clicking on the “Add another medicine” box. In filling the form: ➢ DATES MEDICINES AND REACTIONS ➢ Please fill all Mandatory field(s) (*) STARTED ARE VERY IMPORTANT. ➢ Please indicate the “Weight” if available ➢ Please add any “Additional information” ➢ You can add as many reactions as relevant to this case as stated in the possible by clicking on the “Add another form. reaction/symptom” box. ➢ Click on the “Next page” to proceed to ➢ Please indicate the “Outcome of reaction the “Summary” page. e.g. Recovered/Resolved ➢ View the summary of the report ➢ Please indicate if the reaction(s) led to ➢ Submit by clicking the “Submit” box. any of the following: ➢ After submitting, an acknowledgement is  Caused Hospitalisation-initial or sent by WHO-UMC to the email address prolonged used for reporting the case.  Disabling/or permanent damage ➢ THANK YOU FOR REPORTING  Congenital anomaly/birth defect, Medical devices for pain, other  Life threatening conditions have caused more than 80,000  Death, deaths since 2008  Require intervention to prevent https://www.statnews.com/2018/11/25/medic permanent impairment or disability  Other medically important condition.

9 | P a g e

Pharmacovigilance/Post Marketing Surveillance Newsletter VOL. 13 No.3 2020

al-devices-pain-other-conditions-more-than- 80000-deaths-since-2008/

References i Medical devices https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385 https://www.who.int/medical_devices/full_deffinition/ 582/ accessed 27/08/2020 en/ accessed 25/08/2020 vi https://www.mastercontrol.com/gxp-lifeline/post- ii National Agency for Food and Drug Administration market_monitoring_707/ accessed 27/08/2020 And Control Act Cap N.1 LFN 2004 https://www.nafdac.gov.ng/wp- vii https://www.fda.gov/medical-devices/overview- content/uploads/Files/Resources/Regulations/NAFD device-regulation/classify-your-medical-device AC_Acts/NAFDAC-ACT-Cap-N.-1-LFN-2004.pdf 29/09/2020 accessed 25/08/2020 viii https://www.statnews.com/2018/11/25/medical- iii Global Harmonization Task Force (GHTF) final devices-pain-other-conditions-more-than-80000- Document: Principles of Medical Device deaths-since-2008/ accessed 10/11/2020 Classification ixGeneral Information about Hip Implants http://www.imdrf.org/docs/ghtf/final/sg1/technical- https://www.fda.gov/medical-devices/metal-metal- docs/ghtf-sg1-n77-2012-principles-medical-devices- hip-implants/general-information-about-hip- classification-121102.pdf accessed 25/08/2020 implants#:~:text=There%20may%20be%20adverse %20events%20after%20surgery%2C%20regardless iv Medical Device Reporting (MDR): How to Report ,of%20its%20socket%20in%20the%20hip%20bone Medical Device Problems %20%28pelvis%29 https://www.fda.gov/medical-devices/medical- device-safety/medical-device-reporting-mdr-how- xAdverse events associated with medical devices in report-medical-device-problems#overview accessed patients at different clinics and hospitals in Colombia 29/09/20 https://journals.sagepub.com/doi/abs/10.1177/25160 43519878994?journalCode=cric v Medical Device Postapproval Safety Monitoring Where Does the United States Stand?

10 | P a g e