1440 17 DECEMBER 2021 • VOL 374 ISSUE 6574 science.org SCIENCEINSIGHTS | POLICY FORUMcessing bags remain difficult to obtain. If
this leads to vaccine shortages, countries
may find it more difficult to close im-
munity gaps, increasing the potential for
outbreaks of measles and other vaccine-
preventable diseases ( 4 ).
Products in clinical development, such
as human immunodeficiency virus vac-
cines and next-generation human papillo-
mavirus, tuberculosis, and diphtheria- and
tetanus-containing vaccines, are currently
delayed or at risk of delay owing to disrup-
tions in the manufacture of clinical ma-
terials, the conduct of clinical studies, or
regulatory review.MITIGATION STRATEGIES
We propose these actions to reduce the im-
pact of current disruptions and minimize
the risks of future interruptions in vaccine
s u p p l y.Enabling access to input materials
Access to input materials can be improved
by reducing trade barriers to accelerate
the flow of goods. The COVID-19 Vaccines
Global Access (COVAX) Manufacturing
Taskforce has developed the first virtual
marketplace to match suppliers of critical
input materials with manufacturers of vac-
cines ( 5 ). Approaches to enabling the flowof these and other materials include using
market information to identify specific
materials that require expedited customs
processing; removing import and export
tariffs and other barriers to trade; imple-
menting harmonized coding on critical
consumables to expedite their cross-border
processing ; and eliminating export restric-
tions and prohibitions on critical input
materials, as called for by leaders of the
World Trade Organization and other inter-
national bodies. Such mechanisms are be-
ing used to facilitate access to COVID-19
vaccines. Extending them to the overall
flow of input materials would help ensure
supplies of other important vaccines.Enhancing regulatory capacity
and effi ciency
Regulators must ensure vaccine safety and
efficacy without loss of time. This will re-
quire a combination of greater resources
for regulatory authorities and more ef-
ficient regulatory processes. As dem-
onstrated in the response to COVID-19,
harmonizing processes and expectations
across different regulatory bodies, accep-
tance by one regulatory body of decisions
made by another (referred to as “reliance”),
and eliminating delays between successive
phases of review can drastically acceleratetimelines without sacrificing diligence and
rigor. These practices can be applied more
broadly for other essential vaccines.
In addition, streamlined regulatory pro-
cesses for allowing manufacturers to use
functionally equivalent input materials, such
as stoppers of different colors, would enable
more nimble procurement during shortages.Compiling and disseminating global demand
forecasts for essential non-COVID vaccines
Manufacturers rely on demand forecasts for
planning and to optimize their use of man-
ufacturing capacity. Through the efforts of
WHO, the Pan-American Health Organiza-
tion Revolving Fund, UNICEF, and Gavi,
the Vaccine Alliance, this kind of market
information has become more widely avail-
able in recent years (6–8). Now, as vaccine
supplies and health systems are stretched
thin and the context is evolving rapidly, it
is even more important to keep abreast of
sudden, large changes in demand. This is
especially true for vaccines at risk for dis-
ruptions (see the table); vaccines at risk of
shortages because supply and demand are
too closely matched; and for vaccines with a
potential for demand surges, such as those
used in outbreak response. We suggest
that comprehensive, global demand fore-
casts should be compiled more frequently(^1) Department of Immunization, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland. (^2) MMGH Consulting GmbH, Zurich, Switzerland. (^3) Coalition for Epidemic Preparedness
Innovations, London, UK.^4 Gavi, the Vaccine Alliance, Geneva, Switzerland.^5 Bill & Melinda Gates Foundation, Seattle, WA, USA.^6 Faculty of Medicine, Universidad Nacional Autonóma de México,
Mexico City, Mexico. Email: [email protected]
VACCINES
DISRUPTIONS AS OF
NOVEMBER 2021 RISKS OF FUTURE DISRUPTIONS
Pneumococcal
conjugate vaccines
Short-term disruptions Higher risk. Owing to similarities between conjugation steps and messenger RNA duplication steps, COVID-19
has competed for laboratories and workforce in the past, and this risk has persisted. In this highly segmented
market, delays in production, capacity scale-up, and availability of new products may trigger shortages in countries
that prefer specific products.
Measles-containing vaccines Short-term disruptions Higher risk. If not rapidly addressed, gaps in vaccine coverage are predicted to lead to an increase in measles
outbreaks. Owing to high reliance on one supplier that is also manufacturing COVID-19 vaccines , delays in
production and constrained surge capacity may limit supplies available to respond to these outbreaks, especially
for large countries.
Human papillomavirus vaccine None observed Moderate risk. Regulatory approval and clinical development of three products have been affected because of the
pandemic and travel restrictions, leading to increased risk of delays in availability of those new products.
Diphtheria and tetanus-
containing vaccines,
including pertussis vaccines
Reduced availability
or delays for tetanus-
diphtheria (Td) and
diphtheria-tetanus (DT)
Moderate risk for products containing acellular pertussis (aP) antigens. Owing to similarities in purification
steps, aP may compete with COVID-19 vaccines for materials and equipment. Because the supply of aP-containing
vaccines closely matches demand, any delays or decreases in production may lead to shortages.
Very low risk to supplies of other diphtheria- and tetanus-containing vaccines.
Bacille Calmette-Guérin
vaccine (for tuberculosis)
None observed Low to moderate risk due to increasing market concentration among a small number of prequalified products.
Variability in the manufacturing process may contribute to future shortages of prequalified products.
Rotavirus vaccines None observed Low risk. Because the supply of rotavirus vaccines is increasing, manufacturing delays are not expected
to lead to shortages.
Oral poliovirus vaccines (OPV) None observed Low risk. Risk of future supply delays due to COVID-19 impact in countries where OPV vaccines are manufactured.
Inactivated
poliovirus vaccines
Short-term disruptions Very low risk. Some manufacturers are at risk for supply interruptions, but given the number of different suppliers,
major impacts are not anticipated.
Current and anticipated vaccine supply disruptions
Anticipated disruptions reflect expert judgment informed by aggregated data collected from vaccine manufacturers. See supplementary materials for details.