Primary Vaccine Container Decisions
Defining the Evidence and Framework for Decision Making
How many doses should go in a vaccine vial? It seems like a pretty mundane question, but it’s actually one with a potentially major impact on vaccine systems in low and middle-income countries. What’s more, its a question that, until recently, has gotten far less attention than it deserves. In recognition of the growing importance of this issue, and the need for the viewpoints of many stakeholders to be considered, a roundtable of worldwide experts was convened in Washington, DC on May 9th and 10th to review the available evidence and develop a framework for improving decision-making.
Decisions related to number of doses per vial or container are an obviously important one because they impact on the price of the vaccine, on the amount of cold-chain required to store and transport the vaccine, and on the wastage rate when unused doses from multi-dose vials are discarded. But this issue is really about the “primary vaccine container,” and not just the vial size. Other important aspects of the decision on primary vaccine container include whether to fill the doses in pre-filled syringes or other containers that can deliver the vaccine like the Uniject device and what type of packaging should be used.
The decisions on which vaccines to buy have traditionally be pretty simple. Buyers in low-income countries tended to prefer the least expensive vaccines and ones that required the least cold-chain equipment. As a result, traditional EPI vaccines (e.g, BCG, measles, DTP and polio) have generally come in multi-dose vials (e.g., 10 and 20 doses to a vial) to minimize cost per dose and the immunization logistics impact, including cold chain space and delivery costs. These vaccines typically cost less than $0.20 per dose, and as such the resulting wastage of vaccines had relatively negligible costs. As a consequence, vaccine manufacturers have tended to supply vaccines that respond to the demand for these primary container characteristics.
This balance, however, is rapidly changing. More and more vaccines are being added to the routine immunization schedule in low and middle income countries. By 2015, the GAVI Alliance forecasts that up to 58 of the world’s poorest countries will be using pneumococcal conjugate vaccines at a price to the countries of $3.50 per dose or lower. Because these vaccines are higher priced than the traditional EPI vaccines, wastage becomes a more significant concern.
In this changing environment, data becomes more important and this is really an area where the roundtable will focus a lot of its effort. While wastage data is needed, accurate documentation of wastage rates in developing countries remains limited. One analysis by IVAC researchers of vaccine wastage rates showed a range of 4 to 44% for 10 dose vials and 1 to 10% for single dose vials in 19 GAVI eligible countries (Parmar, 2010). In Bangladesh, wastage rates in selected districts were shown to be an average of 44% (range 16%-77%) for DTP vaccines and even higher for lyophilized vaccines such as BGG and measles (85% and 70%, respectively) (Guichard, 2008).
A recent assessment in India showed an average wastage rate of 27% (with a wide range, from 19% to 58%) for DTP at the service delivery level (UNICEF, 2010). Selection of a vial size (and type of primary container, e.g., vial vs. pre-filled injection device) has important implications that can influence many stakeholders including the vaccine recipient, the vaccine program in a country, the vaccine manufacturer, and the governments or organizations that pay for vaccines. With an emerging need for data, and a framework for organizing and coordinating this data, the time is right for this roundtable of primary vaccine containers.
Primary Container Decisions: Framework
Stakeholders Impacted by Vaccine Vial Size
Presumed Stakeholder Preferences
- Vaccine Manufacturers: Maximize accessibility; profitability preferably, and not to lose money at least; simplicity in terms of supply; clarity on demand from purchasers
- Vaccine Purchasers: Low prices per child vaccinated; low wastage; suitability with country systems; minimal impact on cold chain, transportation and acceptability
- MoH and/or EPI Managers: Low cost per child vaccinated; simple delivery; high client acceptability; low wastage; easy disposal; little impact on cold chain and/or supply chain; improved impact on coverage
- Supply Chain Managers: minimal changes in supply chain needed to accommodate; simple changes where changes needed; reduce wastage
- Health Workers: Easy to handle, transport and administer; low wastage; steady supply; easy to dispose
- Clients (Parents and Children): easy to deliver; less pain
Issues Related to Primary Containers
Previous analyses of vial size have largely focused on cost and volume considerations and have not fully considered the implications of all issues on each of the stakeholders. A systematic analysis of all of the factors impacted by primary container decisions and the tradeoffs to be considered may lead to better decisions that may ultimately improve access to and use of vaccines to prevent death and illness in populations most at risk. There may be different scenarios requiring different solutions, but going through this exercise and identifying the available evidence and gaps can help establish a framework for better decision-making.
Co-chaired by Orin Levine (IVAC) and and Robert Steinglass (John Snow, Inc.)
- To review and synthesize the evidence supporting decisions regarding vaccine container size and type and describe the potential impact on the decision-making process middle and low income countries.
- To develop a putative framework that can be discussed to:
- Identify the key stakeholders who are impacted by a decision and each stakeholders preferences
- Identify the key characteristics of the final product that need to be considered
- Identify the information needed to weigh trade-offs in the decision
- Identify data gaps based on synthesis of evidence and potential framework for evaluation.
IVAC held a 2-day roundtable meeting with about 40 experts and observers. Participants received a packet of materials prior to the meeting to ensure the focus is on new data and discussion. Brief presentations were made at the beginning of the session and followed by moderated discussions about the limitations or gaps in the data and framework for considering primary container decisions.
A summary of evidence and evidence gaps for considering vaccine vial size and additional data needs in the form of a report that could be presented to WHO/SAGE or other policy-making bodies to support their decision-making processes. Meeting minutes and manuscript for a peer-reviewed publication will be developed.
The intent of the meeting was to build on current recommendations and guidelines, identifying where trade-offs must be made to provide more comprehensive generic guidance to all stakeholders regarding in which situations certain primary container presentations would be preferred. Specific evaluations for each product would still be needed, but a better understanding of data gaps and the process for issuing guidance is expected to improve primary container decision making.
Approximately 40 participants who have programmatic experience and/or have conducted studies in the areas of wastage, vaccine safety as it relates to vial size, vaccine policy and economics of various vaccine choice were invited. Experts were a mix of US and European academics and health systems experts, WHO, UNICEF and other partners and MOH/supply chain experts from developing and middle income countries, covering each region. A small number of observers were also present.
Presentation Summaries and Documents
Primary Container Considerations for Prequalification
Andrew Meek, World Health Organization [ View PDF ]
Outlines mandatory, critical, and preferred vaccine characteristics concerning programmatic suitability for WHO prequalification. Addresses removal of preservative thiomersal, including lack of alternatives and consequences of removal on immunization programs. Also describes prequalification and future challenges for Synflorix 2-dose presentation.
Considerations for Primary Vaccine Containers. IFPMA Perspectives: What are the Issues?
Jules Millogo, International Federation of Pharmaceutical Manufacturers and Associations [ View PDF ]
Introduces IFPMA, a nonprofit representing the research-based pharmaceutical industry worldwide. Discusses details of manufacturing, technical, financial, patient and practitioner considerations, and secondary packaging considerations. Concludes stating that parameters for primary container selection are complex and multiple, and patient and provider considerations drive decision-making.
Primary Vaccine Container Selection in Developing Countries Safety
Neal Halsey, Johns Hopkins Bloomberg School of Public Health [ View PDF ]
Addresses surveillance systems for adverse events following immunization, vaccine presentations, preservatives, and contamination and needlesticks. Errors in vaccine administration occur everywhere, although no true rate data exist. Surveillance systems and staff training and supervision are also inadequate. Simpler vaccine administration methods reduce errors. Prefilled single-use syringes are easiest and safest, but also expensive and bulky, and may not be practical. Contamination of multi-dose vials has resulted in outbreaks and deaths globally. Preservatives are effective but have several manufacturing and delivery vulnerabilities.
Primary Vaccine Container Selection Bangladesh Perspectives
Tajul Islam Abdul Bari, Ministry of Health Bangladesh [ View PDF ]
Covers Bangladesh’s vaccine schedule, delivery system, cold chain, multidose vial policy, vaccine wastage, and plans for new vaccine introduction. Bangladesh has no major administration safety problems, although cost, cold chain management, vaccine supply, and vaccine wastage are all important issues for the country.
Primary Vaccine Container Roundtable: Modeling
Bruce Y. Lee, University of Pittsburg [ View PDF ]
Presents the Vaccine Modeling Initiative’s HERMES, a computational tool to design, plan, and manage vaccine supply chains. Discusses impact of rotavirus and pneumococcal vaccine introduction in Niger and Thailand. Other important vaccine supply factors considered are cost, vial size, capacity utilization, and vaccine availability.
Cold Chain, Disposal Volumes, Current Status and Future Trends
S. Kone, WHO/IVB [ View PDF ] [ View PDF - Vaccine Presentations ]
This presentation provides an overview of major elements in immunization systems, along with information about the operations impact of vaccine characteristics such as price, presentation, and formulation. Data from the Democratic Republic of Congo and Chad demonstrate the challenges of vaccine volume changes and increased workload.
Considerations for Primary Container Decisions: DCVMN Perspective
Suresh S. Jadhav, Serum Institute of India / DCVMN [ View PDF ]
Introduces the DCVMN, an alliance of vaccine manufacturers from developing countries that aims to ensure a consistent supply of quality vaccines for developing countries. Presents manufacturers perspectives on cost, vial size, and preservatives. Discusses implications for transition from multidose vials to single dose presentations.
Immunization Session Attendance, Vaccine Wastage and Coverage
Philippe Jaillard, Agence de Médecine Préventive [ View PDF ]
Presents a study conducted by AMP to measure session attendance and calculate wastage in urban and rural areas of Burkina Faso (2009). Main conclusions were: session organization differed by setting, successful strategies exist to limit wastage without reducing coverage, and vial size may be impact quality. Lists areas for further research.
For further questions on the roundtable or framework, please contact Lois Privor-Dumm, Director of Policy, Advocacy & Communications at IVAC.
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