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Progress in Stabilizing Vaccines

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Lyophilization. Spray drying. Liquid formulation. Expectations for future products ... Lyophilization. Progress: ... Lyophilized. 1 2 months. Formulation ... – PowerPoint PPT presentation

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Title: Progress in Stabilizing Vaccines


1
Progress in Stabilizing Vaccines
  • Debra Kristensen
  • PATH
  • TECHNET Consultation Tunis, Tunisia
  • 3 December, 2008

2
Presentation overview
  • Background on PATHs project
  • Progress in vaccine stabilization efforts
  • Lyophilization
  • Spray drying
  • Liquid formulation
  • Expectations for future products

3
PATHs Vaccine Stabilization Project
  • Supported by the Bill Melinda Gates Foundation
  • September 2003December 2010
  • Goal Assess the technical and commercial
    feasibility of converting vaccines used in
    developing-country health programs to
    thermostable formats

4
Project Team
  • Dexiang Chen, Technical lead
  • Hugh Chang, Business
  • Birute Curran, Clinical trials coordinator
  • Abra Greene, Program assistant
  • Mark Guy, Program associate
  • Jeff Huentelman, Administrator
  • Debra Kristensen, Team leader
  • Manjari Lal, Technical officer
  • Emily Lindsay, Project administrator
  • Carol Levin, Economic analyses
  • Heidi Plzak, Laboratory research
  • Scott Priddy, Laboratory research
  • Amy Wales, Communications

PATH Seattle Lab
PATH
5
Project Collaborators
  • Technology companies
  • Ace BioSciences (Denmark)
  • Arecor Ltd. (UK)
  • Aridis (US)
  • Aktiv-Dry (US)
  • BD (US)
  • Cambridge Biostability Ltd (UK)
  • Glide Pharma (UK)
  • HTD Biosystems (US)
  • Nektar Therapeutics (US)
  • Stabilitech (UK)
  • University of Colorado (US)
  • Contract services
  • PPD Development (US)
  • Niro A/S (Denmark)
  • Spring Valley Laboratories (US)
  • Statens Seruminstitut (Denmark)
  • Vaccine producers/projects
  • Crucell (S.Korea, Switzerland)
  • Enterics Vaccine Initiative (US)
  • Indian Immunologicals Ltd (India)
  • Meningitis Vaccine Project (France)
  • Novartis Vaccines (Italy)
  • Panacea Biotech (India)
  • Serum Institute of India (India)
  • Shantha Biotechnics (India)

Current collaborators
6
Reference document
7
Lyophilization
  • Efforts by
  • Celldex, formerly Avant Immunotherapeutics (US)
  • Sapporo University (Japan)
  • Stabilitech (UK)
  • University of Groningen (Netherlands)
  • Vaccine producers
  • Progress
  • Influenza vaccine stable for 26 weeks at room
    temperature1 (University of Groningen)
  • Typhoid vaccine (Ty800) stable for 12 months at
    25C2 (Celldex)
  • Amorij JP, et al. Rational design of an influenza
    subunit vaccine powder with sugar glass
    technology preventing conformational changes of
    haemagglutinin during freezing and freeze-drying.
    Vaccine. 2007 Aug 2925(35)6447-6457.
  • Avant Immunotherapeutics. VitriLife - a long
    term preservation method for biological samples.
    Company
  • information release.

8
Lyophilization
  • Benefits
  • Well established readily available process and
    equipment
  • Often best method for unstable antigens,
    especially bacterial and viral vaccines
  • Challenges
  • Not appropriate for vaccines containing aluminum
    adjuvant
  • Batch limited, process takes days
  • No flexibility, final product is dried cake or
    foam
  • Require storage in the cold chain
  • Reconstitution required

9
Spray-drying
  • Efforts by
  • Aktiv-Dry (US)
  • Aridis Pharmaceuticals (US)
  • BD Technologies (US)
  • Cambridge Biostability Limited (UK)
  • MEND (US)
  • PATH (US) internal research and collaboration
    with all groups listed above except MEND

Laboratory-scale spray drier at PATH
  • Progress
  • Hepatitis B vaccine stable for greater than 24
    months at 37C1
  • Meningitis A vaccine stable for gt 16 weeks at
    40C1
  • 1) PATH unpublished data.

10
Spray-dried hepatitis B vaccine
11
Spray-dried meningitis A vaccine
12
Spray-drying
  • Benefits
  • Works with vaccines containing aluminum adjuvant
  • Possibility of blending spray-dried components to
    make a multivalent vaccine
  • Free flowing powder
  • Flexibility with regard to doses per container
  • Amenable for new delivery technologies
  • Capsule/tablet for oral delivery
  • Inhalation
  • Skin patch
  • Single dose reconstitution devices

Spray dried hepatitis B vaccine
13
Spray-drying
  • Challenges
  • Difficulties applying technology to viral
    vaccines (e.g. years of work with measles vaccine
    have not yielded results superior to
    lyophilization)
  • No commercial products yet produced by aseptic
    spray-drying
  • Vaccine producers reluctant to adopt new
    production methods

Niro A/S
14
Liquid formulations
  • Efforts by
  • Arecor (in collaboration with PATH)
  • Havana University
  • PATH
  • Vaccine producers
  • Progress
  • Synthetic Hib vaccine stable for 3 months at
    37C1 (Havana University)
  • Hepatitis B vaccine stable for gt 6 months at 37C
    and 45C2
  • Freeze protection technology developed by PATH3
  • Verez-Bencomo V, et al. A synthetic conjugate
    polysaccharide vaccine against Haemophilus
    influenzae type b. Science. 2004 Jul
    23305(5683)522-525.
  • Jezek J et al. A heat stable hepatitis B vaccine
    formulation. Vaccine. In press.
  • Jones Braun L, et al. Vaccine. 2008. E-pub ahead
    of print.

15
Freeze protection technology overview
  • Benefits
  • Straightforward formulation Addition of a freeze
    stabilizer.
  • Safe excipients Stabilizers are already widely
    used in licensed products, including parenteral
    medications and vaccines for infants.
  • Broadly applicable All vaccines and diluents
    containing aluminum adjuvant.
  • Low cost excipients The cost of stabilizers is
    negligible US0.0001 per dose of vaccine.
  • Challenges
  • Introduction into existing vaccines requires
    reformulation, clinical trials and regulatory
    approvals.
  • Status
  • Clinical trials planned for two existing vaccines
    (hepatitis B and DTP-HepB-Hib) for registration
    purposes.

16
Freeze- and heat-protected hepatitis B vaccine
(liquid) 12-month stability
FT Three cycles of freezing (-20C, 24 hrs) and
thawing (24C, 4 hrs)
17
Freeze-protection technology placed in the public
domain
18
Vaccines with potential for high temperature
storage
Illustrative estimates based on best stability
data for each vaccine.
19
Maximizing the availability and benefits of
thermostable vaccines
  • Industry and vaccine development projects
  • Incorporate stabilization methods during vaccine
    development
  • Obtain stability and other data required to
    support vaccine storage temperatures other than 2
    to 8C.
  • Public sector
  • Develop out of cold chain procedures, policy and
    equipment (WHO, Technology and Logistics Advisory
    Committee)
  • Provide input to industry with regard to
    desirable target product profiles (VPPAG, vaccine
    introduction projects
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