Vaccine ManufacturingVaccine Manufacturing

Joe BielitzkiJoe BielitzkiNanoScience Technology CenterNanoScience Technology CenterUniversity of Central FloridaUniversity of Central FloridaOrlando, FloridaOrlando, Floridajbielitz@mail.ucf.edujbielitz@mail.ucf.edu

Vaccine needVaccine 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 Adenovirus

Agriculture (animal vaccines)And some live in all categories

Current statusCurrent 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

What’s neededWhat’s needed

New technology? New science? Incorporation of existing

methods? Flexibility? Modularity? Surge capacity? Interdisciplinary approach? Research?

Vaccine shortages Vaccine shortages 2000-20022000-2002

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

Barriers to vaccine suppliesBarriers 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

Vaccine production:Vaccine production:an interdisciplinary probleman 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

Engineering and ScienceEngineering and Sciencejoin forcesjoin forces

Science needs in vaccine productionScience needs in vaccine production Pathways to immunityPathways to immunity Rapid id of immunogenic areasRapid id of immunogenic areas Adjuvants (MyD88, IMD, RIP/FADD)Adjuvants (MyD88, IMD, RIP/FADD) Selective T and B cell responses Selective T and B cell responses

Rate limiting factors in vaccine utilityRate limiting factors in vaccine utility New production tools and methodsNew production tools and methods Immunogen productionImmunogen production Protein stabilityProtein stability Shelf lifeShelf life Storage requirementsStorage requirements

The problemThe problem Vaccine production is slowVaccine production is slow Vaccine manufacturing facilities deal Vaccine manufacturing facilities deal

with one familiar agentwith one familiar agent Lack modularity and flexibilityLack modularity and flexibility Methods are validated and approvedMethods are validated and approved Economics limits new methodologyEconomics limits new methodology

A systems approachA systems approach Identify rate limiting steps in process Identify rate limiting steps in process

Technology bottlenecksTechnology bottlenecks Science bottlenecksScience bottlenecks

Define an ideal vaccine responseDefine an ideal vaccine response Reverse engineer the processReverse engineer the process

ImmunologyImmunology Host and agent needsHost and agent needs Manufacturing needsManufacturing needs Storage and shelf lifeStorage and shelf life Time to productTime to product

What do we know and what do we need to What do we know and what do we need to knowknow

Who knows what nowWho knows what now

A team of scientistsA team of scientistsa fresh looka fresh look

ImmunologistImmunologist MicrobiologistMicrobiologist VaccinologistVaccinologist Systems engineerSystems engineer Bio Process engineer Bio Process engineer GeneralistGeneralist

Study conceptsStudy concepts Report on the status of research for Report on the status of research for

advancing the vaccine manufacturingadvancing the vaccine manufacturing Current production methods and needsCurrent production methods and needs Innovative conceptsInnovative concepts Research needs to facilitate flexibilityResearch needs to facilitate flexibility Research needs to increase surge Research needs to increase surge

capacitycapacity Research needs for modularity (plug and Research needs for modularity (plug and

play)play) Vaccine short comings (as a Product)Vaccine short comings (as a Product)

Race to find new vaccine production techniques in fight against influenza

       The Pharmaceutical JournalVol 275 No 7373 p543-54429 October 2005

Recent IOM Publications Recent IOM Publications Financing Vaccines in the 21Financing Vaccines in the 21stst Century Century

(2003)(2003) Assuring Access and AvailabilityAssuring Access and Availability

Orphans and Incentives (1997)Orphans and Incentives (1997) Developing Technologies to Address Emerging Developing Technologies to Address Emerging

InfectionsInfections

Biological Threats and Terrorism (2002)Biological Threats and Terrorism (2002) Assessing the Science and Response CapabilitiesAssessing the Science and Response Capabilities

there are morethere are more

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