CARIBBEAN REGULATORY SYSTEM VIGICARIB NEWS 18TH AUGUST, 2021 OVERVIEW This issue includes: . Case Safety Reports to VigiCarib Network . CARICOM COVID-19 Vaccine Safety Reports in VigiBase . Summary of Case Safety Reports from CARICOM to WHO Programme for International Drug Monitoring (PIDM) . Global Alerts of Substandard / Falsified Medical Products . COVID-19 Vaccines and Therapeutics: Regulatory Updates . COVID-19 Resources for Regulation and Vigilance Image from Microsoft: https://blogs.microsoft.com/blog/2020/12/11/successful-covid-19-vaccine-delivery-requires-strong-tech- partnerships/ CASE SAFETY REPORTS TO VIGICARIB NETWORK Between 16th July and 16th August, 2021, the VigiCarib network received five (5) case reports of suspected adverse drug reactions (ADRs) and adverse events following immunization (AEFIs): Three (3) ADR reports from Saint Vincent and the Grenadines; Two (2) AEFI reports from Saint Vincent and the Grenadines; One (1) AEFI report from Trinidad and Tobago. In all, 374 case reports have been submitted to the VigiCarib network since its inception in November 2017, consisting of suspected adverse drug reactions (273 – 73%), substandard / falsified medical products (92 – 24.6%), and adverse events following immunization (9 – 2.4%) – Table A1 (See Appendix I in separate document – not publicly available). CARICOM COVID-19 VACCINE SAFETY REPORTS IN GLOBAL DATABASE The following summary presents data on case reports of adverse events following immunization (AEFIs) with COVID- 19 vaccines, based on Individual Case Safety Reports (ICRSs) in VigiBase, the WHO global database. The ICSRs have been submitted by national pharmacovigilance centres in CARPHA Member States with membership in the WHO Programme for International Drug Monitoring (PIDM). The information provided is for descriptive purposes only, e.g. reporting trends. Some of the ICSRs may not have been clinically reviewed or may be pending investigation. Any assessment of an association between COVID-19 vaccines and an increased risk of a given outcome requires additional investigation to get full information. As of 16th August, there were 522 case reports of AEFIs involving COVID-19 vaccines in VigiBase from Barbados (51.9%), Jamaica (46.7%) and St Vincent and the Grenadines (1.3%), primarily involving persons under 65 years (88.7%), and females (397 reports, 76.1%) – Table 1. Most reports were submitted in April – Figure 1. Thirty-four (34) additional reports were submitted in the past month, and the most commonly reported reactions were headache, fever, chills, fatigue, and myalgia – Table 2. 1 Figure 1: Case reports of adverse events following immunization (AEFIs) with COVID-19 vaccines from 1st March to 31st July, 2021. 244 62 Number of AEFI of ReportsAEFI NumberCase 34 60 18 30 6 14 20 21 MAR APR MAY JUN JUL 2021 Serious- Yes Serious- No Ninety-three (93) reports (17.8%) were classified as Serious – Figure 2, Table 3. The individual case safety reports (ICSRs) involved the following vaccines: • COVID-19 vaccine NRVV Ad (ChAdOx1-S recombinant), • COVID-19 vaccine NRVV Ad26 (Gam-Covid-Vac – Sputnik V) and • Covid-19 Vaccine (unspecified). 2 CARIBBEAN REGULATORY SYSTEM Table 1: Patient Age Groups Reported (n=522) Table 2: Top Reported Reaction Terms (n=522) Patient age Count Percentage Top Reported Count Percent 18 - 44 years 225 43.1% preferred terms 45 - 64 years 198 37.9% (MedDRA) 65 - 74 years 40 7.7% PT: Headache 195 37.4% ≥ 75 years 38 7.3% PT: Pyrexia 157 30.1% Unknown 21 4.0% PT: Chills 129 24.7% PT: Fatigue 113 21.6% PT: Myalgia 112 21.5% PT: Arthralgia 99 19.0% PT: Vaccination site 78 14.9% reaction PT: Malaise 78 14.9% PT: Dizziness 77 14.8% PT: Nausea 69 13.2% Figure 2 : Reported AEFI Reactions by Table 3: Seriousness Criteria of Classified Seriousness (n=522) Cases (n=93) Seriousness criteria Count Percent Death 20 3.8% Life threatening 7 1.3% Caused/ prolonged 26 5.0% hospitalization Disabling/ incapacitating 9 1.7% Other medically important 43 8.2% condition Note: Total exceeds 93 due to selection of multiple criteria in individual case reports 3 SUMMARY OF CASE SAFETY REPORTS FROM CARICOM TO WHO PIDM A review of the Uppsala Monitoring Centre’s VigiLyze identified 2,925 case reports from CARICOM countries with membership in the WHO Programme for International Drug Monitoring (PIDM): 522 AEFI case reports, and 2,403 reports of suspected adverse drug reactions (ADRs). Table 4 presents the number of case reports of suspected ADRs and AEFIs submitted to the global monitoring system by Member States between 2007 and August 16th, 2021, inclusive of reports submitted by the CRS on behalf of Member States. Most of the case reports involved adults – Table 5. Between 16th July to 16th August, 2021, 78 case reports were submitted to VigiBase from CARICOM: 34 AEFI reports, 44 ADR reports - Appendix I. Table 4: All VigiBase Reports from CARICOM: Table 5: ICSR Patient Ages Reported suspected ADRs/AEFIs Patient age Count Percent Count Percentage Countries 0 - 27 days 8 0.3% Barbados 1,011 34.6% 104 3.6% Dominica 14 0.5% 28 days to 23 months Guyana 12 0.4% 2 - 11 years 88 3.0% Haiti 16 0.5% 12 - 17 years 42 1.4% Jamaica 1,204 41.2% 18 - 44 years 802 27.4% Saint Vincent and the Grenadines 443 15.1% 45 - 64 years 837 28.6% Suriname 221 7.6% 65 - 74 years 329 11.2% Virgin Islands (British) 4 0.1% ≥ 75 years 245 8.4% Unknown 470 16.1% GLOBAL ALERTS OF SUBSTANDARD / FALSIFIED VACCINES AND MEDICINES In August, the World Health Organization’s Rapid Alert team issued medical product alerts for falsified COVID-19 medical products, including one falsified vaccine identified in Uganda – Table 6. WHO advises regulatory authorities and the public to increase vigilance within the supply chains of countries and regions likely to be affected by these falsified products. Increased vigilance should include hospitals, clinics, health centres, wholesalers, distributors, pharmacies, and any other suppliers of medical products. All medical products for COVID-19 should be obtained from authorized or licensed suppliers, and the product’s authenticity and physical condition should be carefully checked. Patients should be guided to seek advice from a healthcare professional in case of doubt. Additional medical product alerts for non- COVID-19 products are shown in Table 7. 4 Table 6: WHO COVID-19 Medical Product Alerts 2021 Alert number Product Manufacturer Alert summary and date N° 5/2021 COVISHIELD, ChAdOx1 Serum Institute of Batch 4121Z040 - the expiry date (10.08.2021) on this nCoV-19 Corona Virus India Pvt. Ltd. product is falsified [Uganda] August 2021 Vaccine (Recombinant) COVISHIELD 2ml - the genuine manufacturer does not produce COVISHIELD in 2ml (4 doses) N°4 2021 Remdesivir GILEAD Batch EN2005A2-B: the batch number and the expiry date injection100mg/20ml (06/2023) do not correspond to any remdesivir manufactured August 2021 (5mg/ml) by GILEAD. Batch EN2009D7-Q: the batch number does not correspond to any remdesivir manufactured by GILEAD. N°2.2021 COVID-19 Vaccine Pfizer BIONTECH The genuine manufacturer of COVID-19 Vaccine BNT162b2 BNT162b2 confirmed they did not manufacture the product. 26 March 2021 The batch number and expiry dates are falsified. The glass vials and label are different from genuine COVID-19 Vaccine BNT162b2 vials. Table 7: WHO Medical Product Alerts 2021 (Non-COVID-19 products) Alert number Product Manufacturer Alert summary and date N° 3/2021 CYTOTEC 200 microgram Pfizer Batch B16519 – batch number does not correspond to tablets genuine manufactured CYTOTEC. Laboratory analysis of August 2021 samples has also confirmed the product does not contain any active ingredient and does not comply with specifications. Batch 14660 – the expiry date (12/2021) on this product is falsified. N°1.2021 VITAMIN A (RETINOL) -Accucaps The variable data (batch number and expiry dates) of Industries Limited these products do not correspond to genuine 05 March 2021 manufacturing records; -Banner The manufacturing and expiry dates of these products Pharmacaps have been deliberately altered to extend their shelf life; (Canada) Ltd laboratory analysis of both products have confirmed both are underdosed, severely degraded and do not comply with specifications. 5 Identifying a Substandard or Falsified Medical Product (WHO SF products) Some falsified medical products are almost visually identical to the genuine product and very difficult to detect. However, many can be identified by: Examining the packaging for condition, spelling mistakes or grammatical errors; Checking the manufacture and expiry dates and ensuring any details on the outer packaging match the dates shown on the inner packaging; and Ensuring the medicine looks correct, is not discoloured, degraded or has an unusual smell. Patients or consumers should be advised to: Discuss anomalies with a doctor or pharmacist as soon as possible if he or she suspects the product is not working properly or he or she has suffered an adverse reaction; Refrain from buying, receiving or using medicines or vaccines from unauthorized or unregulated sources; and Report suspicious medical products to the National Medicines Regulatory Authority. COVID-19 VACCINES AND THERAPEUTICS: REGULATORY UPDATES Overview of COVID-19 Vaccine Development and Approvals: 110 candidate vaccines are in clinical development: 19 in Phase 3 trials, and 8 in Phase 4 trials. Figure in COVID-19 Vaccines and Therapeutics Regulatory Tracker (Phases tab). Several vaccines have received regulatory approvals in various countries, and 21 vaccine