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

PA

TH/D

ou

ne

Po

rter

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.

Page 3

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

Page 4

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

Page 5

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

Page 6

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.

P

ATH

/Ste

ven

P. D

iesb

urg

PA

TH/J

ames

Bau

er

Abbreviation: R&D, research and development.

Page 7

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

Page 8

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

PA

TH/L

e Th

anh

Hai

Status: Defensive publication precludes blocking patents; prototypes pass all thermal requirements

PA

TH/S

teve

n P

. Die

sbu

rg

Abbreviations: PCM, phase-change material; R&D, research and development.

Page 9

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

Page 10

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.

Page 11

Analysis of other technology solutions

To support broad coverage with freeze-preventive cold chain equipment, we remain impartial to our or others’ potential solutions.

PA

TH/D

ebra

Kri

sten

sen

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

Page 12

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.