Advancing technologies to improve vaccine performance and delivery Darin Zehrung Developing Countries Vaccine Manufacturers Network Meeting Hyderabad India 16 September 2010 Presentation Overview ID: 934478
Download Presentation The PPT/PDF document "Vaccine Technologies at PATH" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Vaccine Technologies at PATHAdvancing technologies to improve vaccine performance and delivery.Darin Zehrung
Developing Countries Vaccine
Manufacturers’ Network Meeting
Hyderabad, India
16 September, 2010
Slide2Presentation OverviewPATH priority areas of focus.Our interdisciplinary approach.Value added vaccine technologies:
Ensure vaccine effectiveness
—
its performance, distribution, and storage.
Improve vaccine delivery safety and waste management.
Address issues of cost.
Opportunities for engagement.
Achieve mutually beneficial collaboration.
Slide3PATH
PATH is an international nonprofit organization that seeks to improve the health of people around the world by advancing technologies, strengthening systems, and encouraging healthy behaviors.
US$253 million annual budget for 2010.
PATH has 31 offices in 22 countries with programs in 70 countries.
Slide4Use of Funds by Areas of Focus*PATH programs in vaccines, vaccine technologies, and immunization account for about one-third of PATH’s annual budget.
Includes vaccine technologies
Vaccine development and access
* Figures are for 2009.
10.1%
13.2%
19.6%
25.0%
32.1%
Slide5Interdisciplinary Approach
Slide6Working together to meet the challenges of safely and effectively delivering vaccines to all who need them in developing countries.
Slide7Value Added Vaccine TechnologiesWe aim to:Ensure vaccine effectiveness.Vaccine performance, distribution, and storage.
Improve vaccine delivery safety and waste management.
Address issues of cost.
Slide8Value Added Vaccine TechnologiesEnsure vaccine effectiveness:Advancing novel vaccine formulations and processing methods.Evaluating the technical and commercial feasibility of improving vaccine
thermostability
.
Developing new equipment to transport, store, and monitor vaccines.
Improve vaccine delivery safety and waste management:
Reducing needle stick injuries and contamination by shielding or eliminating needles.
Assisting minimally trained health care workers with simple devices and user aids.
Lowering risks by enhancing reconstitution methods as well as waste management tools and practices.
Improving vaccine presentations and packaging to meet user needs and minimize environmental impact.
Address issues of cost:Developing and testing effective, low-cost devices that enable reduced dosage and reduce vaccine wastage.
Analyzing the cost-effectiveness of various interventions and strategies to facilitate decision-making, technology uptake, and full immunization.
Slide9Value Added Vaccine TechnologiesEnsure vaccine effectiveness—its performance, distribution, and storage:
Advancing novel vaccine formulations and processing methods.
Evaluating the technical and commercial feasibility of improving vaccine
thermostability
.
Developing new equipment to transport, store, and monitor vaccines.
Improve vaccine delivery safety and waste management:
Reducing needle stick injuries and contamination by shielding or eliminating needles.
Assisting minimally trained health care workers with simple devices and user aids.
Lowering risks by enhancing reconstitution methods as well as waste management tools and practices.Improving vaccine presentations and packaging to meet user needs and minimize environmental impact.
Address issues of cost:Developing and testing effective, low-cost devices that enable reduced dosage and reduce vaccine wastage.
Analyzing the cost-effectiveness of various interventions and strategies to facilitate decision-making, technology uptake, and full immunization.
Slide10Value Added Vaccine TechnologiesEnsure vaccine effectiveness—its performance, distribution, and storage:
Advancing novel vaccine formulations and processing methods.
Evaluating the technical and commercial feasibility of improving vaccine
thermostability
.
Developing new equipment to transport, store, and monitor vaccines.
Improve vaccine delivery safety and waste management:
Reducing needle stick injuries and contamination by shielding or eliminating needles.
Assisting minimally trained health care workers with simple devices and user aids.
Lowering risks by enhancing reconstitution methods as well as waste management tools and practices.Improving vaccine presentations and packaging to meet user needs and minimize environmental impact.
Address issues of cost:Developing and testing effective, low-cost devices that enable reduced dosage and reduce vaccine wastage.
Analyzing the cost-effectiveness of various interventions and strategies to facilitate decision-making, technology uptake, and full immunization.
Slide11Vaccine Technologies at PATHFormulation and Processing Methods.Delivery Technologies.
Packaging and Cold Chain Technologies.
Slide12Formulation and Processing Methods at PATHVaccines: ETEC, hepatitis B, Haemophilus
influenzae
type b, diphtheria-tetanus-
pertussis
(DTP), DTP-hepatitis B-
Hib
, measles, meningitis A,
Shigella. Formulation methods
: Vaccine freeze-protection technology, heat-stable liquid formulation technology, sugar glassification/spray drying, and high throughput screening.
Collaborations:
10 technology collaborators.11 vaccine producers/projects.
12 other organizations (contract labs, universities, etc).
Slide13Technology SpotlightPATH’s vaccine freeze-protection technology:Aluminum adjuvant-containing vaccines can be protected from freeze-damage by inclusion of GRAS
excipients
(propylene glycol, polyethylene glycol 300, or glycerin).
Validated in hepatitis B, DTP, and
pentavalent
(DTP-hepatitis B-
Hib
) vaccines.
Clinical trials with pentavalent vaccine are planned for 2011.Technology is in the public domain.PATH experts are available to provide limited technical assistance to interested manufacturers and researchers.
Slide14Heat- and Freeze-Stable Liquid Hepatitis B Vaccine: 12-Month Stability
Commercial Hep B vaccine
Stable Hep B vaccine formulation
Phosphate, saline
Phosphate, histidine, and propylene glycol
pH 7.0
pH 5.2
Jones Braun L,
Jezek
J, Petersen
S, et
al. Characterization of a
thermostable
hepatitis B vaccine formulation.
Vaccine
.
2009;27:4609
–
4614.
Slide15Improving the Stability of Hib VaccineThe stabilization method:Enhances the stability of
Hib
vaccine by slowing hydrolysis or preventing aggregation.
Improves the stability of
Hib
conjugate vaccine as a component of combination products
(e.g., DTP-hepatitis B-
Hib
).Could be applicable (with modification) to other conjugate vaccines, including those that prevent meningococcal and pneumococcal diseases.
Slide16Delivery Technologies at PATHThermoresponsive gels for sublingual delivery.Dissolvable tablets/wafers for oral vaccines.
Disposable-syringe jet injectors (
DSJIs
).
Prefilled,
autodisable
, and safety syringes.
Nasal and aerosol delivery devices.
Dose-sparing intradermal (ID) delivery devices:
Intradermal adapter for standard needles.Microneedles (hollow, solid, and dissolvable).
DSJIs for ID delivery.
Slide17Delivery Technologies: Our ApproachExploring device landscape (at market and in-development) and research environment.§
Conducting field evaluations to obtain input from end users in developing countries.
Coordinating preclinical and clinical research to demonstrate device performance.
Developing cost models.
Shepherding new devices through relevant regulatory processes.
Devices:
Intranasal delivery; aerosol delivery; transdermal/ID delivery; needle free reconstitution.
Assessments:
Disposable-syringe jet injectors (DSJI); ID delivery devices for rabies vaccine; integrated reconstitution devices.
Regulatory experiences:
US FDA 510(k) process; ANVISA (Brazil
); DCGI
(India); WHO PQS processes.
Research:
MMR; Rabies (ID PEP); IPV (
lD
);
yellow fever
(ID and standard);
DTP-
Hib
.
PATH works with collaborators to improve upon product design and/or advance products through development stages by:
Recent cost analyses:
Inactivated
polio vaccine.*
Three-country cost model on the introduction of DSJIs in routine immunization programs.
* “Improving
the affordability of inactivated poliovirus vaccines (IPV) for use in low- and middle-income countries.” April 2010. Available at
: http://
www.path.org/publications/detail.php?i=1809
.
§
“Intradermal delivery of vaccines: a review of the literature and the potential for development for use in low- and middle-income countries.” August 2009. Available at:
http://www.path.org/publications/detail.php?i=1746.
Slide18Technology Spotlight
Disposable-syringe jet injector (DSJI
):
Focused in Brazil, with activities in India and Oman, the
project aims
to evaluate the suitability and applicability of DSJIs for developing-country immunization programs
.
Working with partners around the world, PATH has:
Conducted user evaluations and pilot introductions.Sponsored
and spearhead clinical trials. Created economic analyses to assist countries with decision-making and uptake of novel devices.
Refined the DSJI value proposition for suppliers and purchasers.
Explored regulatory pathways and assisted in the creation of new specifications.
Slide19Packaging and Cold Chain Technologies at PATHAs new and more expensive vaccines become available, PATH and partners are working to bolster vaccine storage capacity in-country in order to:Protect temperature-sensitive products from damage.
Reduce vaccine wastage for immunization programs.
Help partners to achieve immunization coverage and impact.
Slide20Packaging and Cold Chain Technologies at PATHActivities focus on evaluating and improving vaccine distribution systems, practices, and technologies, for example:Refine vaccine presentations and packaging to meet user needs and minimize environmental impact.
Create forward-thinking strategies and policies for immunization logistics (e.g., Project Optimize—in collaboration with WHO).
Develop and facilitate access to low-cost equipment that appropriately stores, monitors, and transports vaccines.
Vaccine vial monitors (VVM).
Phase-change materials in vaccine storage containers and carrier cases.
Low-cost solar refrigerators (no batteries required).
“Smart” refrigerators that keep vaccines cold yet shield them from freezing.
Slide21Opportunities for EngagementResearch partnerships.Technology transfers.Product consultation and development assistance.Funding opportunities.
Slide22Darin ZehrungPortfolio Leader, Vaccine Delivery Technologies
PATH
dzehrung@path.org
Vaccine Technologies Group
vaccinetech@path.org
Thank you!
Slide23ReferencesPATH. “Improving the affordability of inactivated poliovirus vaccines (IPV) for use in low- and middle-income countries.” April 2010. Available at: http://www.path.org/publications/detail.php?i=1809.PATH. “Intradermal delivery of vaccines: a review of the literature and the potential for development for use in low- and middle-income countries.” August 2009. Available at:
http://www.path.org/publications/detail.php?i=1746
.
Jones Braun L,
Jezek
J, Petersen S, et al. Characterization of a
thermostable
hepatitis B vaccine formulation.
Vaccine. 2009;27:4609–4614.Kristensen D, Chen D. Stabilization of vaccines: lessons learned. Human Vaccines
. 2010;6(3):227–231.Braun LJ,
Tyagi A, Perkins S, et al. Development of a freeze-stable formulation for vaccines containing aluminum salt adjuvants
. Vaccine. 2009 Jan 1;27(1):72-9.Chen D, Kapre
S,
Goel
A, et al.
Thermostable
formulations of a hepatitis B vaccine and a meningitis A polysaccharide conjugate vaccine produced by a spray drying method.
Vaccine
. 2010 (in press).
Sangare
L,
Manhart
L, Zehrung D, Wang CC. Intradermal hepatitis B vaccination
:
a systematic
review and meta-analysis.
Vaccine
. 2009;27(12):1777–1786.
Chi RC, Rock MT, Neuzil KM. Immunogenicity and safety of
intradermal
influenza vaccination in healthy older adults.
Clinical Infectious Diseases
. 2010 May 15;50(10):1331–1338.
Mohammed AJ,
AlAwaidy
S,
Bawikar
S, et al. Fractional doses of inactivated poliovirus vaccine in Oman.
The New England Journal of Medicine.
2010;362(25):2351
–2359.
Slide24Freeze Sensitivity of VaccinesAluminum salt adjuvants—the most prevalent
adjuvants
in human vaccines—irreversibly agglomerate when frozen and then thawed, reducing vaccine potency.
The US Centers for Disease Control and Prevention (CDC) estimates that the federal Vaccines for Children program alone incurs more than
$20 million in vaccine waste annually
from accidental freezing.
Losses due to freeze damage can stress already underfunded vaccine programs in developing countries.
Welte
, M. Vaccines ruined by poor
refrigeration. USA Today. December 4, 2007. Available at
http://www.usatoday.com/news/health/2007-12-04-spoiled-vaccines_N.htm
(accessed 14 January 2010).
Slide25Underscoring Problem and Need
Meta-analysis
of vaccine exposure to freezing: 33 studies.
14%
–
35
% of vaccines exposed to freezing temperatures.
More
rigorous study designs detected more freeze damage (75%–100
%).