COVID-19 VACCINES AROUND THE WORLD - DEVELOPING AND DELIVERING - An information note
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DEVELOPING AND DELIVERING
COVID-19 VACCINES
AROUND THE WORLD
An information note
about issues with trade impact
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
1This information note explores how trade policy can play its part in ensuring the rapid roll-out of vaccine against COVID-19. This document has been prepared under the WTO Secretariat’s own responsibility as a factual overview and is without prejudice to the positions of WTO members or to their rights and obligations under the WTO. Section A Section A provides background information on immunization and the urgent search for vaccines against COVID-19. Section B Section B provides an overview of the development and delivery of vaccines in the form of an infographic. Section C Section C identifies where key decisions with trade impact may need to be made along the vaccine value chain and provides a non- exhaustive list of useful resources to help inform decision-making. This information note was published on 22 December 2020.
SECTION A: Background information
Immunization is a key
component of primary health care
REDUCING GLOBAL
VACCINE IMMUNIZATION MORTALITY IMMUNIZATION
Vaccines are critical Immunization averts Vaccination is The G20 Leaders’
to the prevention and 2-3 million deaths indispensable to end Declaration, issued on
control of outbreaks every year (WHO). preventable deaths 21-22 November 2020,
of infectious diseases of newborns and states: “We recognize
(World Health children under 5 the role of extensive
Organization WHO) years of age by 2030. immunization as a global
public good”.
World trade of vaccines for human
medicine (HS 300220), 2005-19
(Million dollars)
Source: WTO Secretariat
20Vaccination
35000 is currently used to
prevent 20 major
30000 diseases (WHO)
20000
15000
Trade in vaccines for human medicines has
10000 increased five-fold since 2005, according
5000 to the WTO. The WHO estimated global
0 demand for vaccines at 3.5 billion doses
in 2018. This figure excludes the oral polio
vaccine, seasonal influenza and vaccines for
Exports Imports the travel and military markets.
New vaccines typically take more than 10 years to be developed and
Shortages occur regularly. Sixty-nine
approved. COVID-19 vaccines had already been approved for emergency
countries reported vaccine stockouts (i.e. a
use and registered domestically some eight months after this new disease
shortage of at least a one-month duration)
was notified to the WHO. The development of COVID-19 vaccines is
in 2018. Vaccines particularly affected were
following a “pandemic paradigm”, i.e. a compressed timeframe and with
those for yellow fever, measles and polio.
many steps executed in parallel rather than sequentially, according to
the Coalition for Epidemic Preparedness Innovation (CEPI). A first vaccine
candidate was in clinical testing just two months after the publication of
the genetic sequence of SARS-CoV-2, the virus that causes COVID-19
(Nature). To increase the likelihood of finding and approving a safe, effective 12 JANUARY
vaccine a “portfolio approach is being used, i.e. investing in multiple
2020
vaccine candidates for testing. To ensure swift roll-out of an approved
vaccine, manufacturing capacity is being scaled up and production had
commenced even before regulatory approvals were received. According to
CEPI’s manufacturing survey, published in August 2020, there is capacity to On 12 January 2020, the genetic
manufacture at least 2-4 billion doses of COVID-19 vaccines before the end sequence of SARS-CoV-2, the
of 2021. (CEPI manufacturing survey) coronavirus that causes COVID-19,
was published. (WHO)
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
4Ambitious national and global targets have been set for
COVID-19 vaccines. These include, amongst others:
1 BILLION 5 MILLION
doses doses
321
Annual COVID-19 vaccine COVID-19 vaccine
production capacity is production capacity is to
expected to reach 610 reach 5 million doses per
million doses by end 2020 month by January 2021, COVID-19 vaccine
candidates were
and top 1 billion doses in according to the Ministry in development
2021, as per reports from of Health of the Russian according to CEPI as
China’s State Council and of 4 September
Federation (August 2020). 2020.
Xinhua News.
300 MILLION 2 BILLION
6
doses doses
The goal of the US
Government’s Operation According to the WHO and
Warp Speed is to produce Gavi, the Vaccine Alliance,
and deliver 300 million 2 billion COVID-19 vaccine
doses of safe and effective doses are to be distributed
vaccines with the initial by the end of 2021, with an
doses available by January allocation for every country “rights” of vaccine
2021, as part of a broader equal to 20 per cent of the supply-chain
population so as to cover
strategy to accelerate management,
the development, prioritized target groups.
according to
manufacturing, and
distribution of COVID-19 the (WHO)
vaccines, therapeutics,
and diagnostics. Right product
Right quantity
An evaluation by the WTO of the distribution of the vaccine against the 2009 pandemic
influenza A(H1N1) virus (also known as swine flu) highlighted that “specific challenges Right condition
included managing high volumes with limited transportation options, addressing trade
Right place
restrictions and dealing with the impact of national registration processes”. This evaluation
also highlighted difficulties due to a lack of handling facilities to repackage large volumes Right time
of cold-chain deliveries at transit points, such as regional cargo hubs.
Right cost
Vaccines are biological products that are sensitive to environmental conditions. They
can be damaged by conditions such as high or freezing temperatures or by excessive
light, and are effective only for a limited time period at room temperature. Inappropriate
transportation or improper storage reduces their effectiveness. Any break in the chain
of quality would result in weakened or ineffective vaccine and a reduction in the impact
of immunization efforts and of health services as a whole (WHO Vaccine and Biologicals
Guidance).
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
5Successful immunization programmes
“Vaccines are in are built on functional, end-to-end supply
development, but
chain and logistics systems. The role of the
supply chain is to ensure effective vaccine
their ability to end this development, manufacturing, storage,
handling, and stock management; rigorous
pandemic depends on temperature control in the supply chain;
an effective supply chain
and maintenance of adequate logistics
management information systems. The goal
that can connect diverse is to ensure the uninterrupted availability of
quality vaccines from manufacture to delivery,
production locations so that opportunities to vaccinate are not
to the public”. missed due to the unavailability of vaccines
(see WHO).
Frank Appel, CEO, Deutsche Post DHL Group
Declarations and statements made by a
wide range of WTO members have, among
APPROXIMATELY other things, underscored the importance
15k
of well-functioning supply chains and the
need to facilitate cross-border flows of vital
medical supplies and services. According
to the WTO, the World Intellectual Property
Organization (WIPO) and the WTO, the cross-
FLIGHTS, AND
dimensional coverage of various declarations
and statements indicates the importance of a
200k
coherent approach to measures to address
the pandemic.
While recognizing that governments may
take emergency measures to address public
MOVEMENTS BY PALLET health challenges, including shortages of
SHIPPERS, AND COVID-19 technologies, G20 trade ministers
have called upon countries to ensure that any
trade-restrictive measure taken to promote
15m
public health be “targeted, proportionate,
transparent, [and] temporary”.
DELIVERIES IN COOLING BOXES
WOULD BE REQUIRED TO SHIP
10 billion 58
DOSES IN THE STRINGENT AND
CONVENTIONAL SCENARIO. export prohibitions and restrictions enacted
by 43 WTO members and six non-WTO
Source: DHL, McKinsey
members on COVID-19-related medical
Source: DHL White Paper, September 2020. goods or devices remained in force in early
December 2020.
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
6SECTION B:
Overview of the vaccine chain
Infographic
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
7DEVELOPING & DELIVERING
COVID-19 VACCINES AROUND THE WORLD
Universities & NGOs
Institutes Private sector Governments (e.g. corporate
foundations)
Vaccine
development
1
Intellectual
Patents Property (IP*) Exchange of data
& samples
Trademarks
Industrial designs Good laboratory
IP status practice
Trade secrets
& test data
Copyright Vaccine Medical
devices
QUALITY ASSURANCE
IP sharing
(including licensing)
Environmental
risk assessment?
2 Domestic
approval
(Manufacture)
Pharmaceutical
quality
small scale studies
Non-clinical
in vitro in vivo
Clinical trials
I
phase
II III
Evaluation
& decision
safety efficacy
WHO Approval
(including UN by regulator
procurement)
Emergency Emergency use Standard
use listing Pre-qualification authorization approval
3
Domestic
& global Intellectual
Vaccine sourcing Property Quality control
representing up
to 70% of
manufacture manufacturing
time
Export Raw
materials Vaccine
procedures
Several hundred
quality control tests
COVID-19
TRADE
CONTROLS Packaging Packaging Inspection by
materials and labelling regulatory authority
(exporter +
importer)
Import
procedures Approval
by domestic
authority Good
Lot release (Exporter)
manufacturing
practice4
Domestic Domestic approval OR Use step 2 approval
approval
(repeat step 2) (WHO or foreign regulator)
QUALITY ASSURANCE
(Importer) Approved by
regulator
Approval of
manufacture facility
COVAX Approved for market
Public Private (labelling, packaging)
International Transit
5
distribution Cold chain
integrity
A vaccine typically
travels through
Customs IP border several different
measures sites before being
ready for shipment
Shipment
COVID-19
TRADE Good distribution
CONTROLS
practice
Border clearance
QUALITY ASSURANCE
6
Customs & other Inspections
border agency & controls
approval Cold chain
integrity
IP border
measures
Tariffs, other duties Customs release
& charges, decision
internal taxes
Metrology
Distribution
7 Domestic distribution Last-mile
delivery
& surveillance
SUB- Action by health
STANDARD and regulatory
& FALSI-
FIED surveillance Testing
authorities
Action by market
Waste COUNTER-
surveillance &
management FEIT
TRANSPARENCY
enforcement
authorities ESSENTIAL
AT EVERY STEP
Source: WTO, based on EMEA, IFPMA. For clarity of presentation, the different steps in the vaccine value chain are presented sequentially.
To expedite access, in practice, different steps are being undertaken in parallel. *IP may be generated at multiple steps in the vaccine trade value chain.SECTION C:
A checklist of trade issues to consider
along the COVID-19 vaccine value chain
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
10STEP 1
Vaccine development
COVID-19 vaccine candidates are emerging from a global web Enabling these welfare outcomes entails taking into account
of research and development (R&D) partnerships that bring public policy concerns, including the interests of a wide range
together universities and research institutes, non-government of stakeholders, such as start-ups, R&D institutions (both public
organizations, governments, the private sector and international and private), universities and corporations, as well as the
organizations. The diversity and geographic spread of parties interests of funders, whether public or private, and of the public
engaged in R&D is a defining feature of the supply chains that at large, including, in the case of public health, those of patients,
support each step in the vaccine value chain. International who benefit from equitable access to innovation that meets
standards and guidelines support R&D and reflect the current their needs. Each country can tailor its domestic IP system to
state of medical technology and scientific knowledge. its particular needs and circumstances with a view to the public
interest, using the TRIPS Agreement and the flexibilities that it
The International Chamber of Commerce (ICC) emphasized provides (WHO, WIPO and WTO). Some WTO members and
in April 2020 that the COVID-19 pandemic demonstrated the groups of members have made proposals regarding the role of
importance of cross-border scientific collaborations within and the TRIPS Agreement to address the pandemic.
between the public and private sector, and of the effective and
timely global exchange of scientific information, samples and Public and private actors have launched collaborative global
materials. efforts to develop and manufacture therapeutics, vaccines and
diagnostics with the aim of guaranteeing equitable access.
Also in April 2020, the WHO issued a public statement calling Actions include committing to non-exclusive and royalty-free
for collaboration on the development of a COVID-19 vaccine. licensing, or issuing non-enforcement declarations of patent
An R&D blueprint was issued by WHO with the objective of rights in some or all jurisdictions, publishing scientific data on
accelerating COVID-19 diagnostics, vaccines and therapeutics a free-to-use basis, publishing technical specifications of vital
by improving coordination and accelerating the R&D process. equipment (e.g. ventilators) and sharing knowledge.
The WHO also released a concept paper in October 2020
titled “Operationalising the COVID-19 Technology Access Pool
(C-TAP)”. More than
Gavi, the vaccine alliance, is using a so-called “market-shaping” 6,000 registered scientific
approach that seeks to secure a sufficient and uninterrupted studies on COVID-19
vaccine supply, minimize vaccine costs, and ensure appropriate
and quality products. Also noteworthy is the portfolio
approach being taken to vaccine development (WHO). Public
2,262 clinical trials of
COVID-19 treatments
procurement can also be used strategically to foster innovation
in vaccine development. Source: COVID-19 - living NMA
initiative (9 December 2020)
Intellectual property (IP) is created through R&D activities
and may also be generated at multiple steps in the vaccine
trade value chain. Well-functioning and balanced IP systems
42 candidate vaccines
in clinical evaluation
give effect to the WTO Agreement on Trade-Related Aspects
of Intellectual Property Rights’ (TRIPS) objective that the
protection and enforcement of intellectual property rights
should be “conducive to social and economic welfare”.
162 candidate vaccines in
preclinical evaluation
WHO landscape of COVID-19 candidate
vaccines (10 December 2020).
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
11WE, THA, TUR, TWN, UKR,
F
World Map of Clinical Trials
and Partnerships on COVID-19 treatments
JPN: 29
CAN: 70
USA: 439
23
MEX: 61
5
CHN: 211
6
7 6
7
SWE: 4
25 RUS: 37
1 1 2
11 DNK:
GBR:
36
10339 1 1 2
2 NLD: 8
3 DEU:
BEL: 34 69 6 9
41 12
COL: 27 21 1 7 8 2
FRA: 137 14 7
2 1 11 2
6 164 ITA: 70 2
ESP: 18 10
9 20 IRN: 233 10 AUS: 45 4
2 4 IND: 141
PER: 25 1 6 3
ISR: 629 46 3
EGY: 66 1
10
1
2
2 1 2
BRA: 105
2
13 2 6 1 2
ARG: 31 11
1 8
3 2
1
2 1
1
4
ZAF: 26
Source: COVID-19 - living NMA initiative (9 December 2020)STEP
1 Vaccine development
Non-exhaustive list
Possible issues with trade impact to consider of WTO resources1
• Are there policies and regulations in place that promote an effective, timely Agreement on Trade-Related
cross-border exchange of scientific information, data and physical samples Aspects of Intellectual Property
both at the research and development stage and at other steps of the Rights (TRIPS Agreement)
vaccine trade value chain?
Technical Barriers to Trade
(TBT) Agreement
• What actions can be taken to encourage the exchange of data about
COVID-19 vaccines (e.g. studies, clinical trial data, database access) in order WHO, WIPO and WTO (2020),
to facilitate international R&D collaboration? For example, do domestic laws Promoting access to medical
include public interest clauses that allow clinical trial data to be disclosed? technologies and Geneva:
How are “legitimate commercial interests” protected with respect to any Intersections between public
confidential information submitted to regulators? health, intellectual property
and trade (second edition),
• How can access to investigational products (e.g. drugs, plasma and other WHO, WIPO and WTO. See in
medical supplies) needed in COVID-19 vaccine research be facilitated, and particular Chapters II and III
how can the quality and safety of these products be assessed promptly?
WTO information note:
• How can access to the technical know-how (including as embodied in “The TRIPS Agreement and
COVID-19”
international standards) needed in COVID-19 research be facilitated?
• What information exists about the IP, data and knowledge relative to the
development of vaccines, and how can this information be accessed? What
mechanisms are available to incentivize development and support IP-
sharing? Do IP laws provide for research exceptions? What policies apply to
IP ensuing from publicly funded research? What forms of intervention may
be needed to curb or limit IP rights to ensure necessary access and use?
What, if any, access and benefit-sharing regimes for pathogen materials
apply?
• Is there a focal point within the national administration that can answer
requests in relation to establishments licensed to conduct COVID-19- Non-exhaustive list
related vaccine R&D? of other resources
• Are the results of inspections for quality assurance (e.g. good laboratory
practices/good clinical practices and other relevant standards or guidelines) WHO Solidarity Call to Action
shared?
WIPO COVID-19 Policy Tracker
• How can joint ventures and cross-border cooperation in R&D best World Health Assembly
be facilitated so as to contribute to effective vaccine development? resolution WHA73.1
What measures can be taken to promote further investment in vaccine
development, particularly in developing and least-developed countries? WHO Access to COVID-19
Tools (ACT) Accelerator
• How can government procurement best be used as a tool to stimulate
innovation in health care systems, including in the development and supply Medicines Patent Pool
of new or improved vaccines?
Nagoya Protocol on Access
and Benefit-Sharing
WHO PIP Framework
1: This document has been prepared under the Secretariat’s own responsibility and the non-
exhaustive list of resources is reproduced without prejudice to the positions of Members
or to their rights and obligations under the WTO or any of the institutions, agreements or
mechanisms cited.
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
13STEP 2
Domestic approval (Manufacture)
A vaccine usually takes more than
10 years to come to market.
(World Economic Forum) 10
Vaccines are given to healthy individuals, notably infants, as a Regulatory Agency on 2 December 2020, the emergency use
prophylaxis against a subsequent infection. The quality, safety authorization decisions of the US Food and Drug Administration
and efficacy of the vaccine are paramount. According to the taken on 11 and 18 December 2020 and the conditional
COVID-19 Vaccine Global Access Facility (COVAX), a global marketing authorisation given by European Medicines Agency
pooled procurement mechanism for COVID-19 vaccines, on 21 December 2020. Emergency approvals are subject to
managed by Gavi, the Vaccine Alliance, CEPI and WHO, new specific conditions applying to the manufacturer and product
vaccines have an approximately 7 per cent chance of succeeding (e.g. labelling, provision of testing data, lot release procedures)
at the preclinical trial stage. Vaccines are assessed for harmful as determined by the national regulatory authority to ensure
effects not only on humans, but also on the environment. quality, safety and efficacy. An example of a standard approval
decision is the official registration by the UAE Ministry of Health
Vaccines are a diverse class of medical products, so quality/ and Prevention of an inactivated COVID-19 vaccine.
safety evaluation and approval are typically needed on
a product-specific basis. Regulatory requirements vary Vaccine developers may also apply to the WHO Emergency
depending on the type of vaccine, the manufacturing process, Use Listing Procedure (EUL). The EUL is a risk-based procedure
its mechanism of action and the nature of the disease to be for assessing and listing unlicensed vaccines. The process aims
prevented, as well as the target population. In addition to the to assist UN procurement agencies to evaluate available data
preparation itself, for some of the potential COVID-19 vaccine on the quality, safety, efficacy and performance of vaccines.
candidates, approval may also be required for the medical The EUL provides a time-limited listing for unlicensed products
devices used to store and deliver the vaccine (e.g. needle-free in an emergency context when limited data are available and
jet injectors, vials, vaccine storage units, etc.). products are not yet ready to apply for the WHO Vaccine
Prequalification Programme.
Vaccines are approved by the relevant national regulatory
authority in charge of assuring the quality, safety, and efficacy Regulatory measures to limit liability for unexplained adverse
of medical products. Due to the complexity of biotherapeutic reactions may also provide confidence to commercialize
products, their authorization in general requires more and R&D discoveries. A report by the UK’s National Audit Office
larger clinical studies as compared with “small-molecule explains how protection against liabilities and legal action
products”. The WHO has developed specific guidelines for that could arise from any adverse events have been used in
biotherapeutic products and some regulatory authorities also procurement contracts. Similar protections have been agreed
apply specific rules (see WHO, WIPO and WTO). These rules in other procurement contracts (see WEF article)
have been further supplemented with technical guidance
for COVID-19 vaccine developers (e.g. that provided by the Transparency of approval data and decisions is an important
WHO). Once approved for quality, safety, efficacy and the consideration. It is fundamental to ensuring the safety of
appropriateness of the product information (e.g. instructions patients and to ensuring that no product with an unacceptable
for storage and usage), COVID-19 vaccines may also require benefit-to-risk balance will be made available to the public.
a separate marketing authorization distinct from regulatory As described in more detail at Step 4, the national regulatory
approval. The national or regional vaccine approval process authority of an importing country may decide to base its
will in turn be guided by relevant international standards and approval decision on evaluation reports prepared by other
guidelines, including those of the WHO. The TBT Committee’s national or regional authorities, or on those of the WHO
Indicative List of Approaches to Facilitate the Acceptance of the through the EUL or Prequalification Programme.
Results of Conformity Assessment may also be helpful in this
regard. Clinical trial data is generally protected against unfair
commercial use and unauthorised disclosure, and WTO
Two main forms of COVID-19 vaccine regulatory approval members have used policy space within the TRIPS Agreement
are available to developers: authorizations for emergency to apply diverse approaches to data protection. For example,
use, and standard approval by national regulatory authorities. some allow a period of data exclusivity, while others
Emergency use is an accelerated process to grant approval allow regulatory authorities to refer to such data when
for a limited time period (e.g. the duration of the public approving follow-on products. Members have in certain cases
health emergency), based on available scientific information. required the disclosure of clinical trial data in the public interest.
Examples include the authorization for temporary supply
granted by the UK Medicines and Healthcare Products
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
14STEP
2 Domestic approval (Manufacture)
WTO resources
Possible issues with trade impact to consider (non-exhaustive)
• What national legislation is applicable for vaccine approval? Is Agreement on Trade-Related Aspects
there a focal point within the national administration that can of Intellectual Property Rights (TRIPS
answer requests in relation to relevant legislation? Agreement)
• Can emergency-use authorizations be issued? If so, under Technical Barriers to Trade (TBT)
Agreement
what circumstances and conditions? What is the duration of
emergency-use approvals? What liability does the supplier WHO, WIPO and WTO (2020), Promoting
incur? access to medical technologies and
innovation: Intersections between public
• Can emergency-use authorizations be issued for medical health, intellectual property and trade
devices used in conjunction with the COVID-19 vaccine? To the (second edition), Geneva: WHO, WIPO
extent necessary, are liability and compensation schemes in and WTO. See in particular Chapter II.
place?
WTO information note: “The TRIPS
• Does the regulatory authority conduct its own assessment (e.g. Agreement and COVID-19”
health and environmental assessments)? If so, does national law
provide for the possibility of sharing assessments and approval
decisions? What, if any, domestic confidentiality rules apply?
Can information from foreign regulators be used to accelerate
the process?
• Does the regulatory authority conduct its own assessment (e.g.
health and environmental assessments)? If so, does national
law provide for the possibility of expediting assessments,
and sharing both assessments and approval decisions with
regulators in other jurisdictions? What, if any, domestic
confidentiality rules apply? Can information from foreign
regulators be used to accelerate the process?
• What IP access rules apply to clinical trial data? Do IP access
rules for clinical trial data include an exception that allows for
the disclosure of such data if this is in the public interest? What
arrangements are in place for regulatory approval of follow-on
or similar biotherapeutic products manufacturers?
Other resources
(non-exhaustive)
WHO (2020), “Use of Emergency Use
Listing procedure for vaccines against
Covid-19 Q&A”.
Gavi, the Vaccine Alliance (2020), “How
emergency use authorisations could
accelerate access to COVID-19 vaccines”.
Gavi, the Vaccine Alliance (2020), “The
Gavi COVAX AMC: An investment
opportunity”.
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
15STEP 3
Vaccine manufacture
Vaccine manufacture is supported by complex upstream The vaccine market is not a free and open market and is, in fact,
raw material and component value chains. A typical very different from typical pharmaceutical markets, according to
vaccine manufacturing plant will use in the region of 9,000 a 2017 UNIDO and WHO white paper. Vaccines are biological
different materials sourced from some 300 suppliers across products made from living organisms; their development cycle
approximately 30 different countries (estimate from the is quite different from that of a chemical product. Another
International Federation of Pharmaceutical Manufacturers and 2017 report by UNIDO, AVMI and WHO highlights that the risk
Associations). WTO trade statistics suggest that global exports of failure in vaccine product development and production is
of some particularly critical raw materials for vaccine production high. Each stage of the vaccine manufacturing process requires
(including nucleic acids, amino acid phenols, acyclic amides, significant investment and know-how, with packaging and
lecithins and sterols) grew by 49 per cent in the first six months distribution needing the least and bulk antigen production
of 2020 to reach some US$ 15.5 billion in value. the most. In general, the manufacturing process for vaccines is
much more complex than for pharmaceuticals and necessitates
Pharmaceutical companies increasingly rely on third parties for the use of highly specialized facilities and equipment (UNIDO
the timely supply of goods, such as components of medical and WHO).
equipment (e.g. vials, syringes, stoppers) and raw materials (e.g.
active pharmaceutical ingredients), machinery and equipment, The complexity of biotherapeutic products means that it takes
formulated drugs and packaging materials, critical product time for similar biotherapeutic products (SBPs) of approved
components and services. As discussed in AstraZeneca’s vaccines to emerge. A further delaying factor is that proving
2019 Annual Report, all of these raw material inputs are key the safety and efficacy of a vaccine, even if it is a “copy” (i.e.
to operations and are difficult to substitute in a timely manner, an SBP) of an existing one, requires a full regulatory dossier
or at all, and biologics drug substance production (i.e. drugs containing data on pre-clinical and clinical trials. This adds
made made from a living organism or its products) represents time and complexity to the process of making and copying
a particular constraint. Some raw materials are also subject to existing vaccines. As explained by WHO, WIPO and WTO, the
seasonal availability (see the 2015 GlaxoSmithKline plc. article biotherapeutic market is dominated by originator products (i.e.
“Turbocharging the effect of vaccines”) or to other ecological the product that was first authorized – see WHO glossary of
supply constraints (e.g. tachypleus amebocyte lysate). terms).
In view of the complexity of upstream raw material and In 2018, 17 vaccine manufacturers produced vaccines for Gavi,
component value chains, export controls, border clearance and the Vaccine Alliance, with 11 based in Africa, Asia and Latin
transit issues affecting the sourcing of imported raw materials America. Sixteen (38 per cent) of the 42 candidate vaccines
and other essential components could pose difficulties for in clinical evaluation identified in WHO’s draft landscape of
scaling up vaccine manufacturing operations (see Step 5). COVID-19 candidate vaccine in mid-October 2020 involved
Components, raw materials and technology required to (sole or partnered) contributions from non-Organisation for
manufacture vaccines may also be subject to intellectual Economic Co-operation and Development (OECD)-based
property rights (IPRs). Easy access to information about the entities (i.e. China, Cuba, India, Kazakhstan and the Russian
IPR status is essential for manufacturers. It is rare that a single Federation). Forty-five (29 per cent) of the 156 candidate
entity owns all of the IPRs for the components, raw materials vaccines in pre-clinical evaluation involve non-OECD entity
and technology required to manufacture vaccines. Therefore, participation (i.e. Argentina, Bangladesh, Brazil, China, Egypt,
licensing is key to accessing the supplies and technologies India, Kazakhstan, Nigeria, Peru, Romania, Russia, Slovenia,
needed for local production and export. Voluntary licensing Thailand and Viet Nam). The Asian Development Bank (ADB)’s
may facilitate collaboration, partnership arrangements and supply chain map for vaccine manufacturing lists 112 suppliers
technology transfer. Compulsory licensing also remains a policy in 24 countries. (ADB). CEPI’s June 2020 survey of COVID-19
option, (see WHO, WIPO and WTO for more information). vaccine manufacturing capacity identifies capacity in 41
countries.
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
16Since the outbreak of the COVID-19 pandemic, a broad range Public procurement plays an essential role in achieving
of other national and regional measures has been taken to immunization and other public health objectives. The inputs
support investment in COVID-19 relevant production capacity. needed for immunization programmes are limited in range
Measures taken are beginning to appear among the COVID-19 (e.g. vaccines, injection devices, safe disposal containers, cold
support measures communicated by WTO members as part of chain equipment), but have specific characteristics that make
reporting on trade-related developments. their procurement challenging, as already outlined by UNICEF
in 2019. Ensuring that financing and regulatory processes and
Licensing agreements between companies seeking regulatory procurement activities work together to secure timely access
approval for originator products seek to scale up production to products requires the close coordination of stakeholders’
for vaccines when they are approved. Market-shaping actions efforts. The choice of procurement approach can have an
by the Gavi’s COVAX Advance Market Commitment (AMC) important influence on market development.
have facilitated licensing agreements by providing upfront
capital to increase manufacturing capacity (see Gavi’s article of
29 September 2020)
Advance market commitments (AMCs) are a commonly used
measure. These are legally binding contracts whereby one
79
party, such as a national government or Gavi, the Vaccine
Alliance, commits to purchasing from a vaccine manufacturer
a specific number or percentage of doses of a potential
vaccine at a negotiated price, on condition that this vaccine
is developed and licensed and proceeds to manufacture.
These bilateral agreements often secure priority access to
vaccine and manufacturing capacity. AMCs negotiated by
national governments have been criticized on ethical and
medical effectiveness grounds for skewing distribution of
In 2017, low and middle-income
vaccines on the basis of the ability to pay, rather than medical
countries represented 20 per cent of
need. It has also been argued that AMCs support a vaccine
the global vaccine market by value, but
portfolio development approach since governments that enter
79 per cent by volume.
into AMCs for candidate vaccines that do not demonstrate WHO, WIPO, WTO
evidence of safety and efficacy also risk not getting immediate
or sufficient access to successful vaccine candidates. These
concerns have been reflected in declarations and statements
made by some WTO members and groups of members.
A series of initiatives to address local supply-side constraints in
pharmaceutical production have also been given new impetus
by the COVID-19 pandemic. These include the African Union’s
Pharmaceutical Manufacturing Plan which, through the Africa
Medical Supplies Platform, seeks to ensure equitable and
efficient access to critical supplies for African governments
and expand COVID-19-related medical supplies from local
manufacturers. The platform uses pooled procurement – an
approach pioneered by the Pan-American Health Organization
(PAHO) Revolving Fund (RF) in vaccination procurement. Since
1977, the 41 countries and territories participating in the
PAHO RF have pooled their resources to procure high-quality
vaccines, syringes and related supplies for their populations
at the lowest price. The PAHO RF is one of the procurement
channels for the COVAX Facility, which applies the lessons
learned from the PAHO RF by pooling the purchasing power
of its more than 180 participating countries and territories to
leverage access to safe and effective vaccines as soon as they
receive regulatory approval.
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
17STEP
3 Vaccine manufacture
WTO resources
Possible issues with trade impact to consider (non-exhaustive)
• How can access to raw materials, components and other inputs Trade Facilitation Agreement (TFA)
needed to manufacture COVID-19 vaccines be expedited and
costs reduced? Where might export, import and transit controls Agreement on Trade-Related Aspects
hamper the timely sourcing of such inputs and the operation of of Intellectual Property Rights (TRIPS
vaccine manufacturing? Agreement)
Technical Barriers to Trade (TBT)
• What vaccine-related IP rights exist domestically and in export
Agreement
markets? If local capacity exists to manufacture vaccines or
other essential products, how can information about relevant IP WTO information note: “Export
be accessed? What actions or interventions may be needed to prohibitions and restrictions”
facilitate or enable access to and use of necessary IP-protected
technologies? Import Licensing Agreement
• How can governments facilitate technology transfer and local WHO, WIPO and WTO (2020), Promoting
access to medical technologies and
production capacity? How can governments support firms that
innovation: Intersections between public
seek to enter into licensing agreements? health, intellectual property and trade
(second edition), Geneva WHO, WIPO
• Is public sector investment in manufacturing taking place/
and WTO. See in particular Chapter IV.
needed? Is the sourcing of raw materials in inputs by public
sector manufacturers covered by public procurement rules? WTO information note: “The TRIPS
Agreement and COVID-19”
• How can investment be drawn into vaccine manufacturing,
particularly in developing and least-developed countries?
Other resources
(non-exhaustive)
Coalition for Epidemic Preparedness
Innovations (CEPI)
CEPI manufacturing survey (June 2020)
COVAX Facility
Gavi, the Vaccine Alliance: Financing
mechanisms
World Bank: “World Bank Approves $12
Billion for COVID-19 Vaccines”
UNCTAD Tool Box for Policy Coherence
in Access to Medicines and Local
Pharmaceutical Production
WHO: Increasing access to vaccines
through technology transfer and local
production
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
18Quality assurance - a continuous step
Quality assurance is integral to producing safe, efficacious
vaccines. Quality is a broad concept referring to the extent to
which a vaccine fulfils requirements, and safety and efficacy
are attributes of quality.
According to the Innovation Partnership for a Roadmap on Vaccine manufacturers meet quality assurance regulations not
Vaccines in Europe (IPROVE), some 70 per cent of manufacturing only in the “domestic market” (i.e. one in which a regulatory
time is consumed by control testing. Quality infrastructure approval has been given) but also in other countries in which
processes (i.e. accreditation, metrology, standards and these vaccines are licensed, manufactured or sold. Quality
conformity assessment procedures – see technical explanation assurance rules and the processes required to demonstrate
of terms) underpin trade in medical products, providing the compliance can differ from one WTO member to another.
confidence needed between trading partners for commerce Promoting coherence and compatibility of regulations on
to happen. Quality assurance and its supporting processes are vaccines, including by aligning with international standards
based upon relevant international standards and guidelines. and guidelines, is therefore important. For example, more than
100 countries have incorporated WHO good manufacturing
The vaccine trade value chain is highly regulated. Manufacturers, practice (GMP) guidelines into their national laws, but both the
distributors, wholesalers, importers, exporters and other specific provisions of GMP requirements and the compliance
entities are licensed by the relevant national (and regional) procedures are often country-specific. GMP approval in one
authority (or authorities). The issuance of a licence is based country does not confer automatic recognition in another.
on compliance with national (and regional) quality and safety Regulatory divergence further extends across other elements of
regulations (e.g. technical regulations and standards). These conformity assessment, such as sampling methods, inspection
national requirements, in turn, are based upon international protocols, testing results, etc. An additional challenge in
standards and guidance. On-going operational compliance the current COVID-19 pandemic is that sanitary restrictions
is ensured through inspections, testing protocols, certification have reduced the ability of regulatory authorities to conduct
and approval process. Quality assurance extends upstream inspections, both in-country and in manufacturing facilities in
to the raw materials and components needed for vaccine other countries.
production and downstream to post-market surveillance.
Quality assurance and testing of vaccines starts before, and With multiple COVID-19 vaccines on track to secure regulatory
continues well after, the factory gate. approval in various WTO members, but at different times, quality
assurance approval processes merit consideration if prompt
Vaccines are varied in their production processes and the distribution is to be ensured. As per a recent information note
technology they use, e.g. whether they are protein-based, published by the WTO on standards and regulations, various
non-replicating viral vectors or DNA vaccines. Hence the measures to enhance regulatory approval and cooperation
equipment and processes to produce each vaccine differs. on standards for COVID-19-related medical goods have been
Approval of manufacturing facilities is an essential part of the notified to the WTO. These include measures to expedite
regulatory approval process, notwithstanding the fact that regulatory assessments, accept (unilaterally or bilaterally as
a manufacturing facility may already be approved for (other) a result of a mutual recognition agreement) certification and
vaccine production. Regulatory agencies periodically inspect approval already given by other members, and allow for
manufacturing facilities to evaluate compliance with applicable certain flexibilities, such as remote or electronic conformity
regulations and identify potential deficiencies. assessment procedures. A range of options are elaborated in
the TBT Committee’s Indicative List of Approaches to Facilitate
the Acceptance of the Results of Conformity Assessment.
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
19Metrology (i.e. the science of weights and measures), together
SEVERAL
with others pillars of quality infrastructure, is indispensable for
the integrity of the “cold chain”. According to the United States
Center for Disease Control, “assuring vaccine quality and
HUNDRED
maintaining the cold chain is a shared responsibility among
manufacturers, distributors, public health staff, and health-care
providers”. Among the key elements of an effective cold chain
is reliable storage and temperature monitoring equipment. quality control tests are
Vaccine potency is reduced by exposure to improper
conditions, such as to heat, cold or light. Reliable temperature performed on a vaccine
measurements are therefore essential. Calibration testing is
done to ensure the accuracy of a temperature monitoring during its manufacturing
device’s readings against nationally accepted standards.
journey.
Labelling provides vital information related to quality (International Federation of Pharmaceutical
assurance of the vaccine. For instance, labelling traditionally Manufacturers & Associations – IFPMA)
conveys information about product usage, expiry, storage
recommendations, formulation and warnings. For COVID-19
vaccines which require ultra-cold conditions, “smart labels” are
expected to play an essential role in monitoring quality in real
time. A vaccine vial monitor is a special type of smart label which
is described by the WHO as a “label containing a heat‑sensitive
material which is placed on a vaccine vial to register cumulative
heat exposure over time”. According to Gavi, the Vaccine
Alliance, developing high-performance vaccine vial monitors
will be essential for monitoring and ensuring the efficacy of
COVID-19 vaccines that rely on cold chain conditions.
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
20Quality assurance
Possible issues with trade impact to consider
• How can processes to demonstrate compliance agencies that will approve the vaccine be involved in
with quality/safety requirements, such as good their formulation to avoid unexpected difficulties at the
manufacturing practice, be expedited without approval stage? Which procurement methods will be
compromising vaccine safety, quality and efficacy? used?
• How can cooperation between regulatory authorities on • Will customs and other border officials accept suppliers’
the inspection of COVID-19 vaccine production sites be declarations of conformity? If not, what other type
promoted? of certification (e.g. third-party certification) must be
produced for border clearance?
• How can test results, certification and vaccine lot
release systems be operated to meet both international • What measures need to be taken to ensure that local
standards and the requirements of importing countries? testing results and quality/safety assurance samples can
be transmitted back through the vaccine trade value
• What measures can be taken by exporting countries to chain to relevant actors (e.g. regulators and vaccine
promote quality assurance? developers or manufacturers)?
• Can standard labelling and packaging be accepted by • Does the national quality infrastructure ensure accurate
the importing country? and reliable measurements (and other services) to
ensure the integrity of the cold chain?
• How will technical specifications for government
procurement systems be formulated? How can the
WTO resources
(non-exhaustive)
Technical Barriers to Trade (TBT) Agreement
WTO information note: “Standards, regulations and COVID-19 – What actions taken by WTO members?”
WTO TBT Committee discussions on Quality infrastructure
Other resources
(non-exhaustive)
CEPI centralized laboratory network to standardize The Pharmaceutical Inspection Co-operation Scheme
COVID vaccine assessment is a non-binding, informal cooperative arrangement
that shares the results of good manufacturing practice
Gavi, the Vaccine Alliance – Smart labels inspections among its 53 participating authorities.
International Council for Harmonisation of Technical WHO quality assurance of essential medicines and health
Requirements for Pharmaceuticals for Human Use (ICH) products
guidelines on terminology and electronic standards for
the transfer of regulatory information. WHO Expert Committee on Biological Standardization
International Network on Quality Infrastructure (INetQI) WHO documents for SARS-CoV-2 vaccines and other
biologicals
ISO list of national resources to support the fight against
COVID-19 WHO regulatory authority lot release system
The Medical Device Single Audit Program (MDSAP) run WHO guidance for SARS-CoV-2 COVID-19 treatment –
by the International Medical Device Regulators Forum medicines (on quality assurance in general)
allows an MDSAP recognized Auditing Organization to
conduct a single regulatory audit of a medical device WHO vaccine vial monitor
manufacturer that satisfies the relevant requirements
of the regulatory authorities participating in this
international forum.
OECD regulatory quality and COVID-19
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
21STEP 4
Domestic approval
1 BILLION
UNICEF plans to procure 1 billion syringes by the end
of 2021 to guarantee a supply of COVID-19 vaccines.
UNICEF and the PAHO Revolving Fund are coordinating
procurement and supply of vaccine for the COVAX Facility.
(Importer)
35%
The WHO’s global vaccine report identified procurement
delays as being responsible for 35 per cent of vaccine
stockout incidents among middle-income countries in 2018.
Proper regulatory decision-making in a time-efficient manner • Emergency use approval. A regulatory authority can use
could have an important impact on saving lives and mitigating discretionary powers to waive certain product authorization
the COVID-19 pandemic, according to the WHO and UNICEF. requirements to allow importation and marketing on a
Regulatory alignment, collaboration and information-sharing temporary basis (see further discussion of this in Step 2).
will help to facilitate equitable access to safe and efficacious
vaccines that meet international quality and manufacturing • Recognition and/or reliance on the WHO prequalification/
standards. A high degree of cooperation will be required Emergency Use Listing (EUL) decisions. WHO determines
due to the large number of vaccines under development and the acceptability, in principle, of vaccines for UNICEF
countries which could benefit from such vaccines. and other UN agencies through its prequalification
programme. UNICEF procures more than 2 billion doses of
vaccines annually and is coordinating the procurement and
The list of official documents that vaccine manufacturers must
supply of COVID-19 vaccines for the COVAX Facility.
provide the regulatory authorities of importing countries when
seeking approval for a new vaccine, or related medical products,
can be long and includes clinical trial data, registration dossiers, Vaccine procurement decisions by public and private entities
operating licences, product marketing authorizations, quality are entwined with approval processes. Decisions on vaccine
assurance certification and environmental risk assessments. selection, the establishment of immunization schedules,
In addition, requirements are not uniform from one country to demand quantification, the preparation of procurement
another. Formats differ (e.g. electronic, paper and also the way specifications, contract awards and other functions depend
in which clinical trial data must be presented), translations can on approval procedures. With multiple COVID-19 vaccines
take time (e.g. documents will normally need to be completed potentially becoming available on the market, care may need
in the official language(s)), registration timeframes may vary in to be exercised to ensure that best international practices on
duration, and the governmental entities from which approvals government procurement, notably as embodied in the WTO
are required can differ significantly (e.g. the approval of sub- Government Procurement Agreement (GPA), are followed.
national authorities may be necessary). Information about The GPA sets binding minimum standards for transparent,
regulatory requirements may be unavailable, or out of date. fair and open public procurement procedures. The GPA also
includes procedural flexibilities (e.g. shorter time periods
to accelerate procurement and limited tendering) as well as
Regulatory adaptation is critical during public health
general exceptions that can be used to protect human life.
emergencies, and thus the WHO and UNICEF are encouraging
E-procurement and the publication of procurement decisions
national regulatory authorities to modify traditional, reactive
can be helpful in accelerating procurement and enhancing
control systems and to take a proactive, risk-based approach
transparency. They are among the steps already taken by WTO
in order to speed up public access to life-saving medical
members according to information shared with the WTO. Patent
products. To facilitate regulatory alignment and cooperation,
databases may help to inform the procurement of COVID-19
the WHO has developed product-specific roadmaps to assess
vaccine and vaccine-related health products.
the safety, efficacy and quality of candidate vaccines (e.g. that
of Astra-Zeneca). A variety of options exist to speed up the
approval process, including: Knowledge about what intellectual property rights apply in the
importing member, including as determined by its intellectual
• Recognition of and/or reliance on the approval granted by property exhaustion regime, can help to inform the importer
stringent regulatory authorities or WHO-listed authorities about whether voluntary or compulsory licences are needed to
is among the regulatory options available for national ensure the smooth flow of vaccines across borders.
regulatory authorities. The TBT Committee’s Indicative List
of Approaches to Facilitate the Acceptance of the Results of
Conformity Assessment may also be relevant in this regard.
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
22STEP
4 Domestic approval (Importer)
WTO resources
Possible issues with trade impact to consider (non-exhaustive)
• What measures can be taken by importing countries to expedite General Agreement on Tariffs and Trade
(GATT) 1994
the domestic approval of COVID-19 vaccines while ensuring
safety and efficacy? Are domestic approval procedures Agreement on Trade-Related Aspects
published and available, e.g. on the internet? of Intellectual Property Rights (TRIPS
Agreement)
• Can the results of a domestic approval decision taken at Step
2 be accepted and used by the importing country’s regulatory Government Procurement Agreement
authority to approve COVID-19 vaccines and other related (GPA)
products?
Technical Barriers to Trade (TBT)
• Can import approval be based on WHO decisions, including Agreement
vaccine pre-qualification? If the importing country’s regulatory The TBT Committee’s Indicative List of
authority requires foreign-approved COVID-19 vaccines to pass Approaches to Facilitate the Acceptance
through a domestic approval process, can information from of the Results of Conformity Assessment
foreign regulators be used to accelerate this process? Can the (see page 60).
assessment and decision be shared with other countries? Can
emergency-use authorizations be issued for COVID-19 vaccines WHO, WIPO and WTO (2020), Promoting
and related medical devices? Access to Medical Technologies and
Innovation: Intersections between public
• How can intellectual property information related to the vaccine health, intellectual property and trade
be accessed? What intellectual property, if any, applies to the (second edition), Geneva: WHO, WIPO
and WTO. See in particular Chapters II
vaccine in the importing country? For least-developed countries,
and IV
has the temporary exemption from the requirement to protect
and enforce patents and clinical trial data for pharmaceutical
products been implemented domestically? Has a tailored
regime for the exhaustion of intellectual property rights been Other resources
implemented? (non-exhaustive)
• Which entity/entities (both public and private) will take
procurement decisions and how will they be coordinated,
The COVID-19 Vaccine Global Access
including with regard to contract management and the
Facility (COVAX Facility)
distribution of vaccines? How will contract management and
the distribution of vaccines be organized? How can domestic International Coalition of Medicines
approval and procurement decisions be synchronized so as to Regulatory Authorities (ICMRA) acts as a
avoid delays? forum to support strategic coordination
and international cooperation among
• Are appropriate procurement procedures and mechanisms in global medicine regulatory authorities
place to ensure efficient public purchasing of vaccines? How during the COVID-19 pandemic.
can procurement flexibilities in domestic legislation and trade
agreements be used to promote rapid access to an approved The Open Contracting Partnership
Guide collects, publishes and visualizes
COVID-19 vaccine? Which obligations in the WTO trade
COVID-19 procurement data.
agreements (e.g. the Government Procurement Agreement or in
regional trade agreements) continue to apply, if any? The Open Contracting Partnership
findings and recommendations for
• Which procurement methods will be used? Is safety and efficacy better emergency procurement from 12
ensured through use of appropriate technical specifications/ countries
supplier qualification requirements? How is quality control
ensured? Pan-American Health Organization
(PAHO) Revolving Fund
UNICEF vaccine procurement toolbox
UNICEF procurement and shipment
information for COVID-19 related goods
and services
DEVELOPING AND DELIVERING COVID-19 VACCINES AROUND THE WORLD
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