Legal and regulatory framework facilitating vaccine deployment
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JANUARY 2021 Operational guidance:
Legal and regulatory
framework facilitating
vaccine deployment
This document is part of a series of operational guidance
modules developed to support WHO Member States in
the European Region in preparing for and implementing
COVID-19 vaccination. The modules were developed by a
working group convened by the WHO Regional Office for
Europe and consisting of experts from WHO, partner agen-
cies, academia, Member States and other stakeholders.Document number: WHO/EURO:2021-1940-41691-57047
© World Health Organization 2021
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CONTENT
Objectives 1
Rationale 1
Key actions 1
Supporting an efficient regulatory process for COVID-19 vaccines 2
Establishing pathways for emergency regulatory approval of COVID-19 vaccines 2
Facilitating import procedures 4
Expediting lot release of COVID-19 vaccines 4
Ensuring traceability of vaccines 4
References 5
Annex 8Objectives
• to support an efficient regulatory process for COVID-19 vaccines
• to establish pathways to for emergency approval of COVID-19 vaccines
• to expedite lot release procedures
• to ensure vaccine traceability.
Rationale
The number of COVID-19 vaccines receiving emergency use authorisation is expanding.
These are based, in general, on preliminary analyses of Phase III results. In addition, a num-
ber of vaccine candidates use new development platforms and the manufacturing has been
rapidly scaled up. There have been reports of substandard and falsified vaccines in circula-
tion.
A strong regulatory system builds public confidence in health-care professionals and the
quality of products planned for use and protects the population from exposure to substandard
and falsified products or products of limited clinical value. Enabling national regulatory deci-
sion-making in a time-efficient manner will speed up access to life-saving vaccines. It is critical
therefore to involve the national regulatory agency (NRA) or regulatory departments within the
Ministries of Health in COVID-19 vaccine deployment preparedness and implementation.
Emergency use authorization is a special procedure for vaccines granted in the case of a
public health emergency, when less certainty about the efficacy and safety of products is
tolerated, given the epidemiological situation of the disease and the absence of or shortfalls
in treatment and/or prevention options. An important part of emergency preparedness is to
have a plan for how to adapt regulatory pathways and procedures from a traditional, reactive
control system into a proactive, risk-based approach. This chapter reviews such practices
and options; the material presented is a summary of best practice recommendations that
have been drawn from other guidance documents with additional information related to
implementation. The document should be used as supplement to the regulatory guidance
provided in the WHO/United Nations Children’s Fund (UNICEF) interim guidance on devel-
oping national deployment plans for COVID-19 vaccines (1).
Key actions
Enabling decisions on COVID-19 vaccines by the national regulatory authorities in a time-effi-
cient manner should be based on available evidence and should not compromise the existing
processes of regulatory decision-making. National drug regulatory authorities (NRAs) should
conduct an appropriate review of the available data and information and should document the
extent of the evidence in support of the regulatory decision on whether to authorize or reject
the product. Regulatory alignment and collaboration are critical in facilitating rapid and equita-
ble access to safe and effective vaccines meeting international standards.
Predictability of regulatory requirements and early communication of expectations to manu-
facturers of COVID-19 vaccines informs and facilitates preparation of submissions; countries
may refer to considerations for evaluation of COVID-19 vaccines published by WHO (2,3),
the European Medicines Agency (EMA) (4) and stringent regulatory authorities (SRAs) such
as, the United States Food and Drug Administration (FDA) (5) and others as they become
available. In addition to these, WHO has issued a product-specific roadmap that is intended
to serve as a model for subsequent product-specific vaccine evaluations, provided there is
agreement from the manufacturers and the regulators concerned (6).
1New information, linked to development, authorization, use and safety monitoring on
COVID-19 vaccines is evolving. WHO publishes regulatory updates on COVID-19 diagnostics,
treatments and vaccines for NRAs, regional pharmaceutical advisors, regulatory networks
and associated stakeholders (7). Access of countries to product-specific information relat-
ed to WHO procedures of emergency use listing or prequalification (EUL/PQ) of COVID-19
products will be further facilitated; furthermore, documentation related to COVID-19 vaccine
evaluation is being published by some SRAs with the aim of increasing transparency of
regulatory decisions and maintaining public trust. A provisional list of sources of regulatory
information on COVID-19 vaccines is provided in the Annex.
Supporting an efficient regulatory process
for COVID-19 vaccines
The efficiency and effectiveness of the national regulatory process to authorize COVID-19
vaccines can be enhanced by the following general principles and approaches adapted from
WHO guidance (8) and modified to fit the national context:
Target group estimation: ensuring a sound legal basis for regulatory decisions related
to COVID-19 vaccines;
Regulatory alignment and consistency: aligning national regulatory requirements for
COVID-19 vaccine submissions with global best practice, such as WHO recommenda-
tions and/or recommendations of SRAs and applying them in a consistent and predicta-
ble manner;
Regulatory flexibility: reducing time for regulatory approval by defining emergency
pathways and modifying procedures, such as reviewing the submissions and other rele-
vant evidence on a rolling basis;
Regulatory cooperation: establishing links and cooperation agreements to support
the regulatory process by joint review and sharing the tasks with neighbouring NRAs
and/or supporting NRAs;
Regulatory reliance: applying principles of reliance and recognition to decisions and
evidence made available by WHO EUL/PQ procedures and by SRAs to allow efficient use
of resources;
Regulatory agility: adopting proactive search, review and use of the published evi-
dence on COVID-19 vaccines with the aim of supporting regulatory decisions, in particu-
lar decisions based on reliance and recognition;
Regulatory transparency: ensuring transparency of regulatory decisions and of the
available supporting evidence to maintain public trust in the regulatory process and in
the quality and safety of vaccines.
Establishing pathways for emergency regulatory
approval of COVID-19 vaccines
Pathways for emergency regulatory approval should be in place and should have been test-
ed in advance to check that they function properly when needed. An assessment should be
undertaken of the additional human, financial and infrastructure resources required and such
2 resources mobilized promptly.To protect patients and ensure no substandard or falsified products enter the country, it is
critical that existing national legislation relating to importation covers all products including
donations (6). This legislation should be enforced by the NRA as well as customs and other
relevant authorities.
Figure 1 outlines options for pathways for emergency regulatory approval of COVID-19
vaccines depending on prior received authorization by WHO EUL/PQ (9) or by an SRA or
WHO-Listed Authority (WLA) (10).
Figure 1.
Pathways for emergency regulatory approval of COVID-19 vaccines in
non-vaccine-producing countries
COVID-19 VACCINE WAS AUTHORIZED COVID-19 VACCINE
NOT APPROVED
BY WHO EUL/PQ BY WHO EUL/PQ
OR SRA/WLA EUA/CMA DECISIONS OR SRA/WLA
WHO facilitated
Vaccine donations Supporting National NRA
process: collaborative
(no submission of SRA/WLA facilitated owned process
procedure, regional
dossier to NRA) process
joint assessments
Basic requirements: Basic requirements: Basic requirements: Basic requirements:
• product assessment • submission to NRAs • submission to NRAs • submission to NRAs
report of dossiers of dossiers of dossiers and
• lot release docu- • assessment reports • assessment reports product assessment
mentation • MAHs responsible • MAHs responsible reports
• partner commitment for RMP for RMP • manufacturers/
to support the RMP MAHs responsible
(vigillance, traceabil- for RMP
ity, recall) • scientific assessment
by NRA
Procedure: Procedure: Procedure:
Procedure: recognition recognition fast-track
recognition or reliance or reliance / full review
Decision(s): Basic requirements: Basic requirements: Basic requirements:
• import authorization • market authorization • market authorization • market authorization
• lot release or emergency use or emergency use or emergency use
authorization authorization authorization
• import authorization • import authorization • import authorization
• lot release • lot release • lot release
EUA/CMA = emergency use authorization/conditional market authorization;
MAH = market authorization holder; RMP = risk management plan.
3The options draw upon the WHO Guidelines on regulatory preparedness for provision of
the marketing authorization of human pandemic influenza vaccines in non-vaccine-produc-
ing countries (11) and the WHO-UNICEF Joint statement on vaccine donations (12) as well
as the principles of regulatory effectiveness and efficiency outlined above and the basic
requirements of the regulatory process for COVID-19 vaccines (3).
Box 1: Required documentation
As a prerequisite for border and customs clearance, the importing agency or
agent should be equipped to furnish the customs authority with the following
documentation in respect of each consignment.
• documents issued by the NRA in the importing country, attesting that: the
importer is duly authorized to import the medical products; the products are
duly authorized to be marketed or permitted to be imported into the impor-
ting country;
• a batch-release certificate issued by the manufacturer;
• a safety data sheet, where applicable;
• a relevant invoice, bill or delivery slip for the batch, including the product
name, batch number, quantity and expiry date;
• lot/batch release certificate issued by the NRA in the country of origin;
• any other documentation required by national or regional legislation for cust-
oms clearance.
Facilitating import procedures
The WHO Guidelines on import procedures for medical products provide details on legal
responsibility, the legal basis of control, required documentation, and implementation by
national authorities (14).
Expediting lot release of COVID-19 vaccines
The lot release of vaccines by regulatory authorities is part of the regulation of vaccines and
involves the independent assessment of each lot of a licensed vaccine before it is released
for use. This assessment is based, at a minimum, on the review of the manufacturer’s sum-
mary protocol; it may be supplemented by other documents, such as the release certificate
from the responsible NRA or national control laboratory in the country of origin and, in some
circumstances, by independent testing. WHO advises that vaccines procured from assured
sources, for example WHO prequalified vaccines, vaccines listed as EUL, or vaccines ap-
proved by SRAs/WLAs, need not be tested again by receiving countries, as they have been
tested and released already by NRAs with stable, formal approaches for vaccine approval
(13). The WHO operational tool for efficient and effective lot release of COVID-19 vaccines
provides detailed guidance on lot release options (14).
Lot release of COVID-19 vaccines during the pandemic can be based on reliance and recog-
nition and should be done quickly (ideally within two days) through review of the minimum
set of documents (15).
4Ensuring traceability of vaccines
Traceability of COVID-19 vaccines is important for managing distribution of vaccine batches/
lots, individual vaccine administration schedules and safety monitoring. Core data elements
include the name of the product, batch number and the expiry date. Making available stick-
ers, containing printed batch/lot information may facilitate further documentation of tracea-
bility data.
Traceability data elements should be integrated into:
• logistics management documents and information systems to trace vaccine distribution
and manage potential product recalls;
• patient vaccination records, information leaflets, and vaccination reminders to inform
patients of the vaccine received so that a series is completed with the same product;
• adverse event reporting and investigation forms;
• vaccination uptake and coverage monitoring systems;
• COVID-19 disease notification/investigation forms.
Two-dimensional bar codes are already included on the secondary packaging of vaccines
and medicines in many markets to facilitate traceability, and WHO recommends that this
use case be applied for COVID-19 vaccines. Attempt to extend traceability technology to
the vial level would only be optional (and support future operational research) if it does not
compromise statutory information on the vial label. A WHO model label for vials and pack-
aging for Covid 19 vaccines is available in the public domaion (16).
References
1. Guidance on developing a national deployment and vaccination plan for COVID-19
vaccines. Geneva: World Health Organization; 2020
https://www.who.int/publications/i/item/WHO-2019-nCoV-Vaccine_
deployment-2020.1, accessed 11 January 2021
2. Emergency use listing procedure. Geneva: World Health Organization; 2020
https://www.who.int/medicines/publications/EULprocedure.pdf, accessed 11 January
2021
3. Considerations for evaluation of COVID19 vaccines. Points to consider for
manufacturers of COVID19 vaccines. Geneva: World Health Organization; 2020
https://www.who.int/publications/m/item/considerations-for-the-assessment-of-covid-
19-vaccines-for-listing-by-who, accessed 11 January 2021
4. The European Medicines Agency updates on COVID-19.
https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/
coronavirus-disease-covid-19/covid-19-latest-updates
5. U.S. Food and Drug Administration regulatory processes in place to facilitate the devel-
opment of COVID-19 vaccines.
https://www.fda.gov/emergency-preparedness-and-response/coronavirus-dis-
ease-2019-covid-19/covid-19-vaccines
6. Roadmap for evaluation of AstraZeneca AZD1222 Vaccine against Covid-19. Geneva:
World Health Organization; 2020
5https://www.who.int/publications/m/item/roadmap-for-evaluation-of-astrazeneca-
azd1222-vaccine-against-covid-19, accessed 11 January 2021
7. Regulatory updates on COVID-19. Geneva: World Health Organization; 2020
https://www.who.int/teams/regulation-prequalification/covid-19, accessed 11 January
2021
8. Good regulatory practices for regulatory oversight of medical products. Draft working
document for comments. Geneva: World Health Organization; 2020
https://www.who.int/medicines/areas/quality_safety/quality_assurance/QAS16_686_
rev_3_good_regulatory_practices_medical_products.pdf, accessed 11 January 2021
9. Use of Emergency Use Listing procedure for vaccines against Covid-19 Q&A. Geneva:
World Health Organization; 2020
https://www.who.int/medicines/regulation/prequalification/prequal-vaccines/
resources/QA_EUL_Covid-19_July2020.pdf?ua=1, accessed 11 January 2021
10. List of stringent regulatory authorities (SRAs). Geneva: World Health Organization; 2020
https://www.who.int/medicines/regulation/sras/en/, accessed 11 January 2021
11. Guidelines on regulatory preparedness for provision of the marketing authorization
of human pandemic influenza vaccines in non-vaccine-producing countries. Geneva:
World Health Organization; 2016
https://www.who.int/biologicals/expert_committee/PIP_Non-producer_guide_BS_final-
working_version-19102016-clean.pdf, accessed 20 December 2020
12. Vaccine donations. WHO-UNICEF Joint Statement. Geneva: World Health
Organization/United Nations Children’s Fund; 2010
https://www.who.int/immunization/documents/WHO_IVB_10.09/en/, accessed 11
January 2021
13. WHO. Annex 5: Guidelines on import procedures for medical products. In: WHO
Expert Committee on Specifications for Pharmaceutical Preparations. Fifty-third report.
Geneva: World Health Organization; 2019
https://www.who.int/medicines/areas/quality_safety/quality_assurance/WHO_
TRS_1019_Annex5.pdf, accessed 11 January 2021
14. Annex 2: Guidelines for independent lot release of vaccines by regulatory
authorities. WHO Expert Committee on Biological Standardization. Sixty-first report.
Geneva: World Health Organization; 2013
https://www.who.int/biologicals/TRS_978_Annex_2.pdf, accessed 11 January 2021
15. WHO operational tool for efficient and effective lot release of COVID-19 vaccines
https://extranet.who.int/pqweb/sites/default/files/documents/WHO_OperationalTool_
EfficientLotRelease_v20Jan2021.pdf , accessed 25 January 2021)
16. Model packaging for label for vials for Covid 19 vaccines.
https://www.who.int/publications/m/item/model-packaging-for-label-for-vials-for-
covid-19-vaccines, accessed 19 January 2021
6Annex:
Provisional list of sources of regulatory information
1. European Medicines Agency.
a. COVID-19 mRNA vaccine Comirnaty:
Product assessment report; Summary of product characteristics; Risk management plan.
https://www.ema.europa.eu/en/medicines/human/EPAR/comirnaty
b. COVID-19 Vaccine Moderna
CHMP summary of positive opinion for COVID-19 Vaccine Moderna; Product
information; Risk management plan.
https://www.ema.europa.eu/en/medicines/human/summaries-opinion/covid-19-
vaccine-moderna
2. United Kingdom Medicines and Healthcare products Regulatory Agency.
a. Decision on Regulatory approval of Pfizer/BioNTech vaccine for COVID-19:
Conditions of authorization for the Pfizer/BioNTech COVID-19 vaccine; Public
Assessment Report; Information for health-care professionals; Information for
recipients)
https://www.gov.uk/government/publications/regulatory-approval-of-pfizer-biontech-
vaccine-for-covid-19
b. Decision on Regulatory approval of COVID-19 Vaccine Moderna
Conditions of Authorisation for COVID-19 Vaccine Moderna; Information for health-
care professionals; Information for recipients)
https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-
moderna
c. Decision on Regulatory approval of COVID-19 Vaccine AstraZeneca
Conditions of authorization for the Pfizer/BioNTech COVID-19 vaccine; Public
Assessment Report; Information for health-care professionals; Information for
recipients)
https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-
astrazeneca
3. Government of Canada/Health Canada*
a. Pfizer-BioNTech COVID-19 Vaccine
Regulatory Decision Summary
https://covid-vaccine.canada.ca/info/regulatory-decision-summary-detailTwo.
html?linkID=RDS00730
Information for consumers, health care professionals and researchers:
https://covid-vaccine.canada.ca/pfizer-biontech-covid-19-vaccine/product-details
b. Moderna COVID-19 Vaccine:
Regulatory Decision Summary
https://covid-vaccine.canada.ca/info/regulatory-decision-summary-detailTwo.
7
html?linkID=RDS00736Information for consumers, health care professionals and researchers:
https://covid-vaccine.canada.ca/moderna-covid-19-vaccine/product-details
* Other documents, such as “Summary basis of decision”, “Risk management plan”,
“Clinical information” are planned to be made available in the coming weeks or
months.
4. United States Food and Drugs Administration (US FDA)
a. Emergency Use Authorization (EUA) of the Pfizer-BioNTech COVID-19 Vaccine
EUA letter of authorization; Fact sheet for health-care providers; Fact sheet for patients
https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-
2019-covid-19/pfizer-biontech-covid-19-vaccine
Vaccines and Related Biological Products Advisory Committee (VRBPAC), US FDA,
“Pfizer-BioNTech COVID-19 Vaccine” https://www.fda.gov/media/144246/download
b. Emergency Use Authorization (EUA) of the Moderna COVID-19 Vaccine
EUA letter of authorization; Fact sheet for health-care providers; Fact sheet for patients
https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-
2019-covid-19/moderna-covid-19-vaccine
8The WHO Regional Office for Europe
The World Health Organization (WHO) is a spe-
cialized agency of the United Nations created in
1948 with the primary responsibility for internati-
onal health matters and public health. The WHO
Regional Office for Europe is one of six regional
offices throughout the world, each with its own
programme geared to the particular health condi-
tions of the countries it serves.
Member States
Albania
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Azerbaijan
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Bulgaria
Croatia
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Finland
France
Georgia
Germany
Greece
Hungary
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Ireland
Israel
Italy
Kazakhstan
Kyrgyzstan
Latvia
Lithuania
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Malta
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Montenegro
Netherlands
North Macedonia
Norway
Poland
Portugal
Republic of Moldova
Romania
Russian Federation
San Marino
Serbia
Slovakia
Slovenia
Spain WHO/EURO:2021-1940-41691-57047
Sweden
Switzerland World Health Organization
Tajikistan Regional Office for Europe
Turkey UN City, Marmorvej 51,
Turkmenistan DK-2100 Copenhagen Ø, Denmark
Ukraine Tel.: +45 45 33 70 00 Fax: +45 45 33 70 01
United Kingdom Email: eurocontact@who.int
Uzbekistan Website: www.euro.who.int
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