CARIBBEAN REGULATORY SYSTEM

VIGICARIB NEWS

18TH AUGUST, 2021

OVERVIEW This issue includes:

. Case Safety Reports to VigiCarib Network . CARICOM COVID-19 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 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 (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: 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 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 (different nodes) are at various stages of engagement with WHO for emergency use listing (EUL) – Table 8.

 COVID-19 vaccines by 7 emergency authorization holders (sponsors) have been approved by the WHO for Emergency Use Listing (EUL):

• Pfizer-BioNTech: Tozinameran - COMIRNATY™ (EU node); Pfizer-BioNTech COVID-19 vaccine (US node)

• Serum Institute of India: Covishield™ (with technology transfer from AstraZeneca)

• AstraZeneca-Oxford: COVID-19 vaccine AstraZeneca with nodes in South Korea, Europe (Vaxzevria™), Australia, and Japan

• Janssen Biologics B.V: COVID-19 vaccine Janssen

• : COVID-19 vaccine Moderna mRNA-1273

• Beijing Institute of Biologic Products and Sinopharm: COVID-19 vaccine BIBP

• Sinovac Life Sciences: CoronaVac

 CARPHA-CRS has issued recommendations for all the WHO EUL vaccines to Member States to facilitate national regulatory approvals, where needed, with updates including newly

6 approved manufacturing sites and post-listing changes. The most recent recommendation was issued for CoronaVac by Sinovac Life Sciences – Table 8.

 The WHO Strategic Advisory Group of Experts for Immunization has issues interim statements for 3 areas related to the use of COVID-19 vaccines on 10th August, 2021:

• COVID-19 Vaccine Booster Doses: The evidence remains limited and inconclusive on any widespread need for booster doses following a primary vaccination series.

• Fractionated Doses (smaller volumes): There is currently insufficient evidence to recommend the use of fractional doses and at present constitutes this as an off- label use of the vaccine.

• Heterologous priming (different vaccine product used for 2nd dose) for COVID-19 vaccines: WHO recommends that the same vaccine product should be used for both doses, and includes notes for countries that are considering mixing of vaccines (AstraZeneca and mRNA vaccines). If different COVID-19 vaccine products are inadvertently administered in the two doses, no additional doses of either vaccine are recommended. Heterologous priming should only be used if benefits outweigh the risks such as in situations of interrupted vaccine supply. WHO notes that while studies of immune responses are encouraging, they require cautious interpretation given the limited sample sizes and lack of follow up, especially related to safety data, and the uncertain relevance of immunological readouts in relation to clinical impact.

 An overview of COVID-19 vaccines performance against variants of concern (VOC) is provided based on WHO’s Weekly Update: Table 9.

 CARPHA’s COVID-19 vaccine regulatory tracker has been updated to provide an overview of profiles and regulatory approvals for various candidate vaccines and therapeutics. This sheet includes information on the efficacy of the vaccines considering current variants of concern, as per WHO updates.

7 CARIBBEAN REGULATORY SYSTEM

Table 8: COVID-19 Vaccines with Regulatory Approvals by WHO EUL Consideration (15th July, 2021)

Dosing and WHO EUL status WHO Approved Drug Product site(s) Developers (Vaccine name) Vaccine Platform Storage ¥ Authorized by and anticipated

decision date: Recommended by CRS Pfizer-BioNTech mRNA 2 doses I.M. WHO EUL + CRS Baxter Oncology GmbH, Kantstraße 2, 33790 Halle/Westfalen, Germany Approved: 31st INN: tozinameran; BNT162b2 + 97 countries December 2020 -90⁰C to -60⁰C BioNTech Manufacturing GmbH, Kupferbergterrasse 17 - 19, 55116 Mainz, Commercial names: (6 mo.); Germany Additional sites COMIRNATY™; -25°C to -15°C approved: 16th Pfizer-BioNTech COVID-19 (2 wks.) Pfizer Manufacturing Belgium NV, Rijksweg 12, 2870 Puurs, Belgium July, 2021 vaccine 2⁰C to 8⁰C (31 Pharma Stein AG, Schaffhauserstrasse, 4332 Stein, Switzerland days); 30°C (2 hrs) Mibe GmbH Arzneimittel, Münchener Straβe 15, 06796 Brehna, Germany

Pharmacia & Company LLC, 7000 Portage Road Kalamazoo, MI 49001, USA

Hospira Inc., a Pfizer company, 1776 Centennial Drive, McPherson, Kansas 67460, USA AstraZeneca-Oxford + SK Recombinant 2 doses I.M. WHO EUL + CRS SK Bioscience Approved: 15th Bioscience (supplier) ChAdOx1-S 2°C to 8°C (6 + South Korea 150, Saneopdanji-gil, Pungsan-eup, Andong-si, Gyeongsangbuk-do, Republic of February (AZD1222) adenoviral vector mo.) for COVAX / Korea PAHO Serum Institute of India + Recombinant 2 doses I.M. WHO EUL + CRS Serum Institute of India Pvt. Ltd Approved: 15th AstraZeneca-Oxford ChAdOx1-S + 45 countries 212/2, Off. Soli Poonawalla Road, Hadapsar Pune, Maharashtra, (India) - 411028 February University adenoviral vector 2°C to 8°C (6 (AZD1222; Covishield™ mo.) Janssen-Cilag (Johnson & Viral vector (non- 1 dose I.M. WHO EUL + CRS Janssen Biologics B.V., Einsteinweg 101, 2333 CB Leiden, The Netherlands Approved: 12th Johnson) (JNJ-78436735) replicating) + 59 countries March; -25°C to -15°C Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium (24 mo.) Aspen SVP., 8B Gibaud Road, Korsten, Port Elizabeth 6020, South Africa

2-8°C (4.5 mo. Catalent Indiana LLC., 1300 S Patterson Drive, Bloomington. Indiana (IN) 47403, within shelf- USA. life) Grand River Aseptic Manufacturing Inc. 140 Front Ave. SW. Grand Rapids, Michigan (MI) 49504, USA.

Catalent Anagni S.R.L., Fontana del Ceraso SNC, Strada Provinciale 12, Casilina 41, 03012 Anagni, Italy. AstraZeneca-Oxford Recombinant 2 doses I.M. WHO EUL + CRS Catalent Anagni, Località Fontana del Ceraso, S.P. Casilina, 41 03012, Anagni (FR), Approved: 16th University (AZD1222) ChAdOx1-S + 121 countries Italy April Commercial name: adenoviral vector 2°C to 8°C (6 VAXZEVRIA™ mo.)

8

Dosing and WHO EUL status WHO Approved Drug Product site(s) Developers (Vaccine name) Vaccine Platform Storage ¥ Authorized by and anticipated

decision date: CP Pharmaceuticals, Ash Road North, Wrexham Industrial Estate, Wrexham LL13 9UF, United Kingdom

IDT Biologika, Am Pharmapark, Dessau-Rosslau 06861, Germany

SK Bioscience, 150, Saneopdanji-gil, Pungsan-eup, Andong-si, Gyeongsangbuk-do, Republic of Korea

Universal Farma, S.L. (“Chemo”), C/Del Tejido, 2, Azugueca de Henares, Guadalajara, 19200, Spain

Amylin Ohio LLC (AZ), 8814 Trade Port Drive, West Chester, OH 45071, USA Moderna & NIAID mNRA-based in 2 doses I.M. WHO EUL + CRS Rovi Pharma Industrial Services, S.A., San Sebastián de los Reyes, Paseo de Europa, Approved: 30th (mRNA-1273) lipid nanoparticle + 68 countries 50, 28703. San Sebastián de los Reyes, Madrid, Spain April INN: Elasomeran (LNP) -25°C to -15°C (7 mo.); Baxter Pharmaceutical Solutions, LLC, 927 S. Curry Pike, Bloomington, IN 47403, Additional sites ModernaTX, Inc/ USFDA USA. approved: 6th COVID-19 mRNA vaccine 2-8°C (30d) or August, 2021 9-25°C (12h) Catalent Indiana, LLC, 1300 South Patterson Drive, Bloomington, IN 47403, USA Sinopharm + China National Inactivated virus 2 doses I.M. WHO EUL + CRS Beijing Institute of Biological Products Co., Ltd. Approved: 7th May Pharmaceutical Group + + 60 countries No. 6 (East Part) and No. 9 (West Part), Boxing 2nd Road, Beijing Economic and Beijing Institute of Biological 2°C to 8°C (24 Technological Development Area, Beijing, the People's Republic of China, 100176. Products (BBIBP-CorV) mo.) Sinovac COVID-19 vaccine Inactivated virus 2 doses I.M. WHO EUL + CRS Sinovac Life Sciences Co., Ltd., No. 21, Tianfu Street, Daxing Biomedicine Industrial Approved: 1st June (Vero Cell [Inactivated]) – 2°C to 8°C (12 + 39 countries Base of Zhongguancun Science Park, Daxing District, Beijing, P.R.China. Commercial name: CoronaVac mo.) AstraZeneca-Oxford Recombinant 2 doses I.M. WHO EUL + CRS Catalent Anagni S.R.L., Località Fontana del Ceraso S.P. Casilina, 41 03012 Anagni Approved: 9th July University (AZD1222)/ TGA, ChAdOx1-S + 121 countries (FR) Italy. Australia adenoviral vector 2°C to 8°C (6 mo.) IDT Biologika GmbH, Am Pharmapark, Dessau-Rosslau 06861 Sachsen-Anhalt, Germany.

Seqirus Pty Ltd., 39-79 Poplar Road Parkville, Vic, 3052 Australia.

CP Pharmaceuticals Limited, Ash Road North, Wrexham Industrial Estate. Wrexham LL13 9UF, UK. AstraZeneca-Oxford Recombinant 2 doses I.M. WHO EUL + CRS Catalent Anagni S.R.L., Contrada Fontana del Ceraso 03012. Anagni, Italy. Approved: 9th July University (AZD1222)/ MHLW, ChAdOx1-S + 121 countries Japan adenoviral vector 2°C to 8°C (6 Daiichi Sankyo Biotech Co., LTD., Kitamoto Site. 6-111, Arai, Kitamoto City, mo.) Saitama, Japan.

KM Biologics Co. Ltd., Koshi Production Center. 3766-1, Sakae, Koshi-shi, Kumamoto, Japan.

9 Dosing and WHO EUL status WHO Approved Drug Product site(s) Developers (Vaccine name) Vaccine Platform Storage ¥ Authorized by and anticipated

decision date: WHO EUL status – Pending/Not under review yet (Not eligible for CRS review)

Gamaleya Research Institute Adenovirus Viral 2 doses I.M. 71 countries Not applicable Anticipated date to & Russian Health Ministry vector (non- be set (Sputnik V) replicating) 2°C to 8°C CanSino Biological Inc + Adenovirus; Viral 1 dose I.M. 8 countries Not applicable Rolling data Beijing Institute of Biological vector (non- starting August Products (Convidicea (Ad5- replicating) 2°C to 8°C 2021 nCoV)) NOVAVAX (NVX-CoV2373) Protein subunit 2 doses I.M. None to date Not applicable Pre-submission 2°C to 8°C meeting held Sinopharm + China National Inactivated virus 2 doses I.M. 2 countries Not applicable Pre-submission Pharma. Group + Wuhan meeting held Institute of Biol. Products 2°C to 8°C CureVac (Zorecimeran: mRNA-based in 2 doses I.M. None to date Not applicable Planned for Q4 of CVnCoV/CV07050101) lipid nanoparticle 2°C to 8°C 2021 Vector State Research Ctre of 2 doses I.M. 2 countries Not applicable Pending expression Virology and Biotech. of interest (EpiVacCorona) 2°C to 8°C Anhui Zhifei Longcom Recombinant 2 or 3 Doses 2 countries Not applicable Additional Biopharmaceutical, China + (protein subunit) I.M. information IMBCAMS (ZF2001) 2°C to 8°C requested Bharat Biotech + Indian Whole virion 2 Doses I.M. 9 countries Not applicable Rolling data Council of Medical Research inactivated 2°C to 8°C started 06 July (ICMR) () 2021 Pasteur CoV2 preS Recombinant, 2 Doses I.M. None to date Not applicable Planned for 9 July dTM-AS03 vaccine adjuvanted 2°C to 8°C 2021 Clover Biopharmaceuticals Protein subunit 2 doses I.M. None to date Not applicable In discussion on Inc. + GSK + Dynavax (SCB- 2°C to 8°C submission 2019) strategy and timelines BioCubaFarma – SARS-CoV-2 spike 2 doses None to date Not applicable In discussion on (Soberana 01, protein I.M. submission Soberana Plus, Abdala) 2°C to 8°C strategy ¥ - Storage information is provided primarily for sealed vials. See product information for additional details on storage and handling. References: McGill COVID19 Vaccine Tracker. COVID-19 Vaccines. Updated 13th August 2021. Available at: https://covid19.trackvaccines.org/. World Health Organization. Status of COVID-19 Vaccines within WHO EUL/PQ evaluation process. Updated 15th July 2021. WHO, Geneva, 2020. Available at: https://www.who.int/teams/regulation- prequalification/eul/covid-19. World Health Organization. Draft landscape of COVID-19 candidate vaccines. WHO, Geneva, 13th August 2021. Available at: Draft landscape of COVID-19 candidate vaccines (who.int).

10 Table 9: Summary of vaccine performance against variants of concern (VOC) relative to ancestral stains- 10th August, 2021

-

-

-

Cova

-

-

-

-

-

CorV

-

1273

-

Covishield

Developers Developers (Vaccine name) ZL Anhui Recombinant AstraZeneca Vaxzevria CNPG Beijing BBIBP Bharat Covaxin Gamaleya V Sputnik Janssen 2.5 Ad26.COV Moderna mRNA Novavax vax Pfizer BioNTech Comirnaty SII – Sinovac CoronaVac Alpha (B.1.1.7) Summary of VE* Protection retained against all outcomes Severe disease ↓1 ↔1 ↔3 Symptomatic disease ↔ to ↓3 ↔1 ↓1 ↔3 ↔ to ↓2 ↔1 ↔2 Neutralization ↔2 ↓3 ↔1 ↔1 ↔1 ↔2 ↔10 ↔1 ↔ to ↓28 ↔ to ↓5 Beta (B.1.351) Summary of VE* Protection retained against severe disease; reduced protection against symptomatic disease; limited evidence Severe disease ↔1 ↔1 Symptomatic disease ↓↓↓1 ↔1 ↓↓↓1 Infection ↔1 ↔ to ↓2 Neutralization ↔ to ↓3 ↓↓5 ↔ to ↓2 ↓1 ↓↓1 ↓ to ↓↓5 ↓ to ↓↓2 ↓↓↓1 ↓ to ↓↓28 ↓ to ↓↓4 Gamma (P.1) Summary of VE* Unclear impact; very limited evidence Severe disease Symptomatic disease Infection ↔1 Neutralization ↔1 ↓1 ↓2 ↓4 ↔ to ↓3 ↔ to ↓3 Delta (B.1.617.2) Summary of VE* Protection retained against severe disease; possible reduced protection against symptomatic disease and infection; limited evidence Severe disease ↔1 ↔1 Symptomatic disease ↓↓2 ↓1 ↔ to ↓3 Infection ↓1 ↓1 Neutralization ↔ to ↓2 ↓ to ↓↓3 ↔ to ↓2 ↓3 ↓3 ↓7 ↓1 ↓ to ↓↓2 Extracted from WHO Weekly Epidemiological Update: Edition 52 and 10th August 2021. Available at: https://www.who.int/publications/m

Arrows generalize the magnitude of reduction in VE or neutralization: “↔” <10% reduction in VE, or VE >90% with no comparator, or that there was a <2-fold reduction in neutralization; “↓” 10 to <20% reduction in VE, or 2 to <5-fold reduction in neutralization; “↓↓” 20 to <30% reduction in VE, or 5 to <10-fold reduction in neutralization; “↓↓↓” ≥30% reduction in VE, or ≥10-fold reduction in neutralization. When more than one neutralization study is available, the interquartile range (25th and 75th percentiles) of fold-reductions across all studies for specific vaccine/variant was used. The number of studies is shown in parentheses.

11 CARIBBEAN REGULATORY SYSTEM

Additional notes on VOC impacts on vaccines table • Studies presenting VOC specific VE estimates are assessed against a comparator VE estimate to determine level of reduction in VE. For symptomatic disease, VOC VE is compared against phase 3 randomised RCT results from non-VOC settings. For severe disease and infection, VOC VE is compared to non-VOC VE estimates from the same study when available (or to Alpha VE from same study when assessing Beta, Gamma, or Delta); with an exception for AstraZeneca Vaxzevria for severe disease (phase 3 RCT efficacy estimates against severe disease are used as comparator since within study comparator is unavailable) and for infection (phase 3 estimate of VE against infection due to non-VOC is available and used as comparator). In some instances, a study may be included for severe disease or infection even without a comparator if very high VE estimate against a VOC is reported (i.e., >90%).

• It is also important to note that studies vary in population, outcome definitions, study design and other methodological considerations, which may in part explain differences when comparing VE estimates between different studies. In addition, the reductions presented consider VE point estimates only and do not take into account the uncertainty around these estimates. The reductions in VE noted should be interpreted with these limitations in mind.

Extracted from WHO Weekly Epidemiological Update: Edition 52 and 10th August 2021. Available at: https://www.who.int/publications/m.

COVID-19 RESOURCES FOR REGULATION, CAPACITY-BUILDING AND VIGILANCE

Technical Resources for Regulation, Capacity-Building and Vigilance of COVID-19 Vaccines and Therapeutics

Resource Description and Link CARPHA COVID-19 This page provides media releases on regional responses to COVID-19, CARPHA Situation Webpage Reports, and Technical Guidance: https://www.carpha.org/What-We-Do/Public- Health/Novel-Coronavirus. CARPHA CRS VigiCarib Adverse Events Following Immunization: VigiCarib Vaccine Reporting Form Online Reporting Forms Adverse Drug Reactions, and Substandard / Falsified / Unregistered Medical Products: VigiCarib Reporting Form

PAHO COVID-19 Webpage The interactive graphic on this page will lead you to technical guidance, systematic reviews of candidate therapies, COVID-19 vaccine updates on development URL: https://www.paho.org/en/topics/coronavirus-infections/coronavirus-disease- covid- 19-pandemic PAHO Technical URL: https://www.paho.org/en/technical-documents-coronavirus-disease-covid-19. Documents

PAHO Ongoing Living This is a summary of evidence on potential therapeutic options for COVID-19, examines Update of Potential 129 therapeutic options. COVID-19 Therapeutics URL: https://iris.paho.org/handle/10665.2/52719?locale-attribute=pt 24th Edition (6th August)

WHO Technical WHO guidance documents published in Technical Report Series (TRS) for the Guidance documents for development, production and evaluation of candidate COVID-19 vaccines. evaluation of COVID-19 URL: https://www.who.int/teams/health-product-and-policy-standards/standards- Vaccines and- specifications/vaccine-standardization/

12

WHO Strategic Advisory COVID-19 Vaccine Technical Documents Group of Experts on URL: https://www.who.int/groups/strategic-advisory-group-of-experts-on- Immunization (SAGE) immunization/covid-19-materials

WHO Technical Relevant WHO documents for SARS-CoV-2 vaccines and other biologicals Documents for Vaccines URL: https://www.who.int/biologicals/Relevant_WHO_documents_for_SARS-CoV- and Biologicals 2_vaccines_and_other_biologicals.TZ.IK.7_Apr_2020.pdf

WHO COVID-19 Vaccines The COVID-19 vaccine safety guidance manual of Global Advisory Committee on Vaccine Safety Surveillance Safety (GACVS). Manual. URL: https://www.who.int/publications/i/item/10665338400

WHO Regulatory Updates General page URL: https://www.who.int/teams/regulation-prequalification/eul/covid- on COVID-19 19

WHO Guidelines for URL: Medicine Donations https://www.who.int/selection_medicines/emergencies/guidelines_medicine_donations/ (Emergencies) en/ WHO Lot Release of URL: https://www.who.int/biologicals/areas/vaccines/lot_release/en/ Vaccines by NRAs WHO Model packaging for URL: https://www.who.int/teams/regulation-prequalification/eul/covid-19/covid-19- COVID-19 vaccines – WHO model- packaging working position

INFORMATION

This newsletter is produced by the technical team of the CARPHA Caribbean Regulatory System for the focal points of CARPHA Member States, drug safety officers, immunization programme managers, public health administrators and CARPHA staff with an interest in the safety and quality of medicines and vaccines. A public version may be posted, however not all content shared with focal points will be publicized.

Technical Officer: Kerrine Ottley

Editor: Dr. Rian Marie Extavour

Email: [email protected]

Website: https://carpha.org/What-We-Do/CRS/VigiCarib

13