Developing and advancing freeze-preventive vaccine carriers
Third WHO Global Forum on Medical Devices
Steven P. Diesburg
Product Development Engineer
May 12, 2017 Photo here
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Po
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Rubella
Typhoid PS
JE live
Temperature sensitivity of vaccines
Freeze dried
Liquid, no adjuvant
Liquid, with alum
adjuvant
Vaccine formulation
Rotavirus
Rotavirus
HPV
Pneumo PS-PCV
JE inactivated
Measles
OPV
BCG
Hib
HepB
DTwP
Penta- valent
T, DT, dT
Rabies
Yellow fever
MenA PS-PCV*
Hib
Least sensitive
Most sensitive
Vaccines to the left of the line are not damaged by freezing
Most sensitive
Least sensitive
Heat sensitivity
Freeze sensitivity
HepA
Influenza inactivated IPV
MMR
Varicella- zoster virus
DTaP Hexa- valent
MenC PS-PCV
*The diluent for MenA PS-PCV contains alum adjuvant and is freeze sensitive.
Cholera inactivated
Not sensitive
This slide and information are taken directly from a 2014
presentation available at http://www.who.int/immunization/programmes_systems/supply_chain/resources/Vaccin
eStability_EN.pdf adapted by Julie Milstein and John Lloyd from earlier WHO and PATH
publications.
Abbreviations: BCG, bacillus Calmette-Guérin; dT, diphtheria (low-dose), tetanus; DT, diphtheria, tetanus; DTaP, diphtheria, tetanus, acellular pertussis; DTwP, diphtheria, tetanus, whole-cell pertussis; HepA, hepatitis A; HepB, hepatitis B; Hexavalent, DTaP-HepB-Hib-IPV; Hib, Haemophilus influenzae type b; HPV, human papillomavirus; Influenza, influenza (inactivated, split vaccine); IPV, inactivated poliovirus vaccine; JE, Japanese encephalitis; Men A, meningitis A; Men C, meningitis C; MMR, measles, mumps, rubella; OPV, oral poliovirus vaccine; Pentavalent, DTwP-HepB-Hib; Pneumo, pneumococcal; PS, polysaccharide; PS-PCV, PS-protein conjugate vaccine; T, tetanus.
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Freezing is prevalent in the cold chain
Abbreviations: BCG, bacillus Calmette-Guérin; PCV, pneumococcal conjugate vaccine; UNICEF, United Nations Children’s Fund.
In studies that examined all segments of distribution, 75% to 100% of vaccine shipments were exposed to freezing temperatures
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1. Raise global awareness.
2. In-house research and development (open access).
3. Assist manufacturers; de-risk technologies.
4. Support device specifications and requirements.
5. Analyze other technology solutions.
PATH’s multilevel approach
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PATH’s efforts to raise global awareness
• Helped develop WHO’s cold chain temperature monitoring protocol.
• Assisting countries in conducting temperature monitoring studies to identify cold chain issues.
• Creating training materials and job aids.
• Publishing and distributing research.
Video is available at: http://www.path.org/media/above-zero.php
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In-house R&D, open access
• Research and development of a freeze-
preventive liner for existing, low-cost vaccine
carriers
• PATH developed a method to formulate
vaccines so they are not freeze-sensitive.
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Abbreviation: R&D, research and development.
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Tem
per
atu
re (
°C)
Abbreviations: Amb, ambient; Int., internal; Mid, middle. R&D, research and development.
Minimum rate ambient temperature test with freeze-preventive vaccine carrier prototype
Confirmatory laboratory test at PATH of freezing in a currently available vaccine carrier with
non-conditioned ice packs (thermal “worst case”)
Lowest measured temperature probe in the vaccine storage compartment of the carrier
Tem
per
atu
re (
°C)
Ambient
Time (hours)
Time (hours)
In-house R&D, open access
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In-house R&D, open access
1. In 2012, PATH field tested a removable, freeze-preventive liner in Vietnam using a PCM. • Successful proof-of-concept.
• However, there are issues with PCMs and removable components.
2. By 2015, PATH had redeveloped an integrated, freeze-preventive design using only foam and water (testing with -25°C ice packs at +10°C ambient).
3. In early 2016, a solution (including PCM or water) was defensively published through Research Disclosure to ensure open access to the technology.
Water and foam liner with housing
PCM-filled liner
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Status: Defensive publication precludes blocking patents; prototypes pass all thermal requirements
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Abbreviations: PCM, phase-change material; R&D, research and development.
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Assisting manufacturers; de-risking
Continued design, engineering, and market support of multiple manufacturers to accelerate introduction
Status: Risk analysis testing recently completed with one manufacturer; hard-tooling is moving forward
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The E004 section on WHO’s PQS website contains detailed specifications for both current vaccine carriers and freeze-preventive vaccine carriers (draft specifications).
PATH has been providing technical support and participating in a working group to support the creation of the new freeze-preventive vaccine carrier specification and verification protocol.
WHO PQS specifications documents are available at: http://apps.who.int/immunization_standards/vaccine_quality/pqs_catalogue/catdocumentation.aspx?id_cat=18.
Supporting device specifications and requirements
Status: Freeze-preventive vaccine carrier documents are finalized and near release
Abbreviation: PQS, Performance, Quality and Safety.
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Analysis of other technology solutions
To support broad coverage with freeze-preventive cold chain equipment, we remain impartial to our or others’ potential solutions.
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PATH:
• Often receives and responds to external
requests for partnership, quick analysis,
and expert opinions.
• Is part of a multi-agency working group for
which we provide analysis and access to
laboratory testing.
• Avoids favoring particular manufacturers
or the technologies we help introduce.
Status: Non-partnering entities have alternate
product designs; we continue to provide feedback
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For more information
• PATH Vaccine and Pharmaceutical Technologies site. Available at http://sites.path.org/vpt/
• Report on the Freeze-Preventive Passive Container Meeting. Available at http://www.path.org/publications/detail.php?i=2570
• Special Issue of Vaccine on Building Next Generation Immunization Supply Chains. Available at http://www.sciencedirect.com/science/journal/0264410X/35/17
• Freezing temperatures in the vaccine cold chain: A systematic literature review. Available at http://www.sciencedirect.com/science/article/pii/S0264410X07002289
• Effects of freezing on vaccine potency: Literature review. Available at http://www.path.org/vaccineresources/details.php?i=1158
• Forecast Report: Freeze-Safe Vaccine Carriers—Modeling the Potential Global Market. Available at http://www.path.org/vaccineresources/details.php?i=2133
• Research Disclosure: Freeze-prevention design for vaccine carriers, cold boxes and other passive cold chain equipment to prevent freezing of vaccines, drugs or pharmaceuticals in the cold chain. Available at https://rd.orbit.com/OrderForm/PublicationPreview.aspx?disNum=622008
• Development of a freeze-stable formulation for vaccines containing aluminum salt adjuvants. Available at http://ac.els-cdn.com/S0264410X08014163/1-s2.0-S0264410X08014163-main.pdf?_tid=4529a0b8-3038-11e7-b8ea-00000aacb35d&acdnat=1493840569_958e4f3072dd957a55544403b1664624
Disclosure: This work was written by PATH and supported in whole or part by a grant from the Bill & Melinda Gates Foundation. The views expressed herein are solely those of the authors and do not necessarily reflect the views of the Foundation.