Vaccine Manufacturing

1
Vaccine Manufacturing

• Joe Bielitzki
• NanoScience Technology Center
• University of Central Florida
• Orlando, Florida
• jbielitz_at_mail.ucf.edu

2
Vaccine need

• Infectious diseases of public health interest
• Rotavirus
• Measles, mumps, rubella
• Diphtheria, pertussis, tetanus
• Polio
• Emerging diseases
• HIV
• SARS
• WNV
• Bio-threat agents
• Smallpox
• Anthrax
• Plague
• Infectious diseases of regional concern
• Tick borne encephalitis
• Japanese encephalitis
• Infectious diseases of concern to the military
• Dengue
• Malaria

And some live in all categories
3
Current status

• For the usual products-supply and demand
• For the others wait and see
• Discovery through Commercialization
• Not linked
• Production is limited
• Single or limited methodology
• cGMP
• Little innovation
• Market forces restrict change
• Intellectual property law
• Regulatory process

4
Whats needed

• New technology?
• New science?
• Incorporation of existing methods?
• Flexibility?
• Modularity?
• Surge capacity?
• Interdisciplinary approach?
• Research?

5
Vaccine shortages 2000-2002

• DTaP
• Two producers stop
• Thimerosal removal
• Td
• One producer stops
• MMR
• Sole producer has GMP issues
• Varicella
• Alteration to production facilities
• Pneumococcus
• Demand exceeds supply
• Influenza
• Difficulty growing virus
• Increased demand due to change in target
  population age -65 to 50
• QC issues at one producer

6
Barriers to vaccine supplies

• Exit and concentration (multinationals)
• Loss of current producers
• mergers
• Research and development
• Return on investment
• IP
• Barriers to entry
• Cost of trials
• Discovery firms are small
• Regulation
• Need updating
• Cost benefit is questioned
• Undervaluation of vaccines
• Return on investment
• Capacity prior to license
• Prophylaxis vs therapy

7
Vaccine productionan interdisciplinary problem

• Bringing new science to the table
• Adjuvants
• Protein stability
• Linked development schemes
• Pathways to immunity
• Looking at production
• Immunogen production
• Permissive cells
• Contamination/cross contamination
• Protein stabilization
• A systems problem without a systems approach
• Entrenched production methods
• Shelf life wet vs dry refrigerated vs ambient
• Benefits for the future
• Improved immunity
• Increased surge capacity
• Ability to deal with novel and new threats
• Changing paradigms for an uncertain future

8
Engineering and Sciencejoin forces

• Science needs in vaccine production
• Pathways to immunity
• Rapid id of immunogenic areas
• Adjuvants (MyD88, IMD, RIP/FADD)
• Selective T and B cell responses
• Rate limiting factors in vaccine utility
• New production tools and methods
• Immunogen production
• Protein stability
• Shelf life
• Storage requirements

9
The problem

• Vaccine production is slow
• Vaccine manufacturing facilities deal with one
  familiar agent
• Lack modularity and flexibility
• Methods are validated and approved
• Economics limits new methodology

10
A systems approach

• Identify rate limiting steps in process
• Technology bottlenecks
• Science bottlenecks
• Define an ideal vaccine response
• Reverse engineer the process
• Immunology
• Host and agent needs
• Manufacturing needs
• Storage and shelf life
• Time to product
• What do we know and what do we need to know
• Who knows what now

11
A team of scientistsa fresh look

• Immunologist
• Microbiologist
• Vaccinologist
• Systems engineer
• Bio Process engineer
• Generalist

12
Study concepts

• Report on the status of research for advancing
  the vaccine manufacturing
• Current production methods and needs
• Innovative concepts
• Research needs to facilitate flexibility
• Research needs to increase surge capacity
• Research needs for modularity (plug and play)
• Vaccine short comings (as a Product)

       The Pharmaceutical JournalVol 275 No 7373
p543-54429 October 2005
13
Recent IOM Publications

• Financing Vaccines in the 21st Century (2003)
• Assuring Access and Availability
• Orphans and Incentives (1997)
• Developing Technologies to Address Emerging
  Infections
• Biological Threats and Terrorism (2002)
• Assessing the Science and Response Capabilities
• there are more

Recent Non-IOM publication Vaccines Frontiers in
Design and Development (2005) Moingeon, P.