Vaccine101, Dynport Vaccine Company LLC


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This slideshow was created by April Finnen of Dynport Vaccine Company LLC of Frederick, Maryland and was shared with me for the purposes of my column on

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  • Dear Mrs April,
    Good Day

    We are a pharma consultancy agency working with many pharma companies in all over the world specially in Middle east and North African Countries (MENA Countries).
    Currently we are very interested to source a high reputed vaccine manufacturing company as a business partner for one of our clients in MENA markets whom they are very interested and immediately ready to establish a manufacturing facility for vaccines in their home country.
    I kindly introduce to you our business understanding and preview for this cooperation with your respected company.

    1- Our Client is ready to bring all needed finance to the facility and to do all needed legal and regulatory steps with local authorities to have all necessary licenses and approvals to start this project.
    2- The candidate partner ( Looking to be your company) will be giving the needed technical support and technical know how and to have share in the management of this facility, and will be taking agreed percentage share from the ownership of this facility.
    3- Markets will be mainly Middle East and North African countries i.e: S. Arabia, Gulf countries, Jordan, Iraq, Lebanon, Syria, Egypt, Libya, Tunisia, Sudan Algeria, Morocco, and other African countries.
    4- We will be ready to expose to you our client details and to sign our NDA agreement.

    In case you are interested to go in further details, please reply to me so we can go for more discussions and to agree on action plan that will be implemented to materialize this project with agreed time lines frames.

    I am ready to travel immediately to meet you and all related management in your esteemed company and discuss all details.

    I am looking for your kind feedback and reply.

    Note: I have attached to you short profile about our activities.
    Best Regards

    Dr. Ayman Abu Ghunaim
    Managing Director
    Erada Pharma Consultancy
    Jordan - Amman

    Mobile: 00962796246773

    Skype: dr.ayman.abu.ghunaim
    Are you sure you want to  Yes  No
    Your message goes here
  • This presentation was condensed from a series of Vaccine 101 presentations designed for employees at DynPort Vaccine Company (
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Vaccine101, Dynport Vaccine Company LLC

  1. 1. Vaccine 101 July 22, 2009 DynPort Vaccine Company LLC, A CSC Company
  2. 2. Overview <ul><li>Vaccines and how they work </li></ul><ul><li>Making a vaccine </li></ul><ul><li>Vaccine manufacturing </li></ul><ul><li>Putting things together </li></ul><ul><li>Biodefense and vaccines </li></ul>
  3. 3. Vaccine 101 Vaccines and How They Work
  4. 4. What is a Vaccine? <ul><li>A vaccine is a biological material intended to induce a specific immune response in humans or animals. </li></ul><ul><li>Vaccines work because the body’s immune system “remembers” how to protect itself from microbes it has previously encountered. </li></ul><ul><li>Vaccines are one of the greatest success stories in public health. </li></ul><ul><ul><li>Vaccines have ended smallpox, and lowered the incidence rates of serious illnesses including diphtheria, tetanus, measles and polio by more than 95% since the beginning of the 20 th century. </li></ul></ul>DVC has experience with many kinds of vaccines.
  5. 5. Some Types of Vaccines <ul><li>“ Live” vaccines include a live variant of the target pathogen. </li></ul><ul><ul><li>Live attenuated vaccines: recombinant DNA technology removes critical pieces of the virus or bacteria genome to make it less virulent. </li></ul></ul><ul><ul><li>Subunit vaccines: made using only part of the virus or bacteria. </li></ul></ul><ul><li>Recombinant vaccines – proteins expressed in various mediums including E. coli and yeast, likely to be a heterogenous mixture of strains </li></ul><ul><li>DNA vaccines – employ the genes that code for specific antigens (antigen = a substance that stimulates immune response, particularly production of antibodies) </li></ul><ul><ul><li>No DNA vaccines have been licensed, though several are in clinical testing </li></ul></ul><ul><li>Combination vaccines – combine protection against several diseases (e.g., MMR  measles, mumps and rubella) </li></ul>
  6. 6. Vaccine 101 Making a Vaccine
  7. 7. From Test Tube to FDA Review Source: CDER Handbook, FDA 3/16/98,
  8. 8. Advanced Development <ul><li>All DVC products are transitioned from research labs after early research and development, including proof-of-concept. </li></ul><ul><li>DVC specializes in “advanced development” of vaccines. </li></ul><ul><ul><li>Encompasses nonclinical and clinical research, and all activities up to and including licensure by the U.S. Food and Drug Administration (FDA). </li></ul></ul><ul><li>Biopharmaceutical development is lengthy and expensive. </li></ul><ul><ul><li>On average, 10 to 15 years and nearly $600 million.* </li></ul></ul>Advanced Development *Source:
  9. 9. Animal Studies in Vaccine Development - Terminology <ul><li>Nonclinical research </li></ul><ul><ul><li>Proof-of-concept animal models (does it work?) </li></ul></ul><ul><ul><li>Toxicology, including acute/repeat-dose, and reproductive (is it safe?) </li></ul></ul><ul><ul><li>Efficacy/immunogenicity (will it protect against disease?) </li></ul></ul><ul><ul><li>Product testing using animals (is it potent and stable?) </li></ul></ul><ul><li>Preclinical research </li></ul><ul><ul><li>Any nonclinical study conducted prior to use of the product in humans </li></ul></ul>
  10. 10. Why Can’t Computers and Cell Cultures Replace Animal Research? <ul><li>Animal and non-animal models both used to answer biological questions. </li></ul><ul><li>Animal studies may pave way for computer models. Computer models and cell culture may extend what is learned in animals. </li></ul><ul><li>Computer models and cell culture still don’t reflect the complexity and dynamics of a living organism. </li></ul><ul><li>A complete answer currently requires animal studies. </li></ul>DVC ensures that no animal will suffer needlessly, and that the fewest animals are used to obtain scientifically defensible data.
  11. 11. Types of Animal Studies <ul><li>Dose and schedule requirements </li></ul><ul><ul><li>Animal data supports effective dose in humans </li></ul></ul><ul><li>Toxicology – is it safe? </li></ul><ul><ul><li>Includes reproductive toxicology </li></ul></ul><ul><li>Efficacy – does it work? </li></ul><ul><ul><li>Demonstrate that the vaccine actually works under its intended conditions of use (dose and regimen) </li></ul></ul><ul><ul><li>Demonstrates that the vaccine </li></ul></ul><ul><ul><ul><li>Protects against what it was designed to protect against </li></ul></ul></ul><ul><ul><ul><li>Protects against a certain level of challenge </li></ul></ul></ul><ul><ul><ul><li>Protects for a certain period of time </li></ul></ul></ul>
  12. 12. Human Clinical Trials <ul><li>Human clinical trials are required by the FDA to test drugs and biologics (including vaccines) in humans. </li></ul><ul><li>The Food, Drug and Cosmetic Act requires drug manufacturers to prove that products are safe for human consumption and effective for a specific indication before licensure and marketing in the U.S. </li></ul><ul><li>After (years of) successful nonclinical research, the Sponsor submits an Investigational New Drug (IND) application to the FDA, which within 30 days either: </li></ul><ul><ul><li>Notifies the Sponsor of deficiencies and places a clinical hold, or </li></ul></ul><ul><ul><li>Does not notify the Sponsor, which means it is OK to start the clinical trial. </li></ul></ul>
  13. 13. Phases of Clinical Trials <ul><li>Phase 1 </li></ul><ul><ul><li>Evaluate safety and tolerability of the investigational product in humans </li></ul></ul><ul><ul><li>Involves 20 to 80 normal, healthy volunteers </li></ul></ul><ul><ul><li>Typically closely monitored </li></ul></ul><ul><ul><li>Designed to determine the metabolism and pharmacologic actions or drugs, side effects associated with increasing doses, and (if possible) gain early evidence on efficacy </li></ul></ul><ul><li>DVC has successfully advanced 8 products into clinical trials in the last 10 years. Phase 1 trials completed include: </li></ul><ul><ul><li>Anthrax vaccine </li></ul></ul><ul><ul><li>Botulinum neurotoxin vaccine </li></ul></ul><ul><ul><li>Butyrylcholinesterase (chemical defense therapeutic) </li></ul></ul><ul><ul><li>Influenza vaccines (seasonal and pandemic) </li></ul></ul><ul><ul><li>Tularemia vaccine </li></ul></ul><ul><ul><li>Smallpox vaccine </li></ul></ul>
  14. 14. Phases of Clinical Trials (continued) <ul><li>Phase 2 </li></ul><ul><ul><li>Evaluate safety and effectiveness for a particular indication </li></ul></ul><ul><ul><li>Typically involves several hundred subjects at multiple sites </li></ul></ul><ul><ul><li>Controlled study </li></ul></ul><ul><ul><li>DVC products in Phase 2: botulinum, plague and tularemia vaccines </li></ul></ul><ul><li>Phase 3 </li></ul><ul><ul><li>Expanded controlled trial </li></ul></ul><ul><ul><li>Involves several hundred to thousands of subjects, multiple sites </li></ul></ul><ul><ul><li>Long-term safety and efficacy </li></ul></ul><ul><ul><li>DVC product in Phase 3: seasonal influenza vaccine (Baxter) </li></ul></ul><ul><li>Phase 4 – clinical evaluation is ongoing, even after FDA licensure </li></ul><ul><ul><li>Post-marketing studies </li></ul></ul><ul><ul><li>Ongoing safety evaluation </li></ul></ul>
  15. 15. Proving Safety and Efficacy in Humans <ul><li>Safety </li></ul><ul><ul><li>Safety assessments in study volunteers include: </li></ul></ul><ul><ul><ul><li>Physical exam, vital signs, blood pressure </li></ul></ul></ul><ul><ul><ul><li>Clinical laboratory assessments: hematology, serum chemistry, urinalysis, pregnancy test for females </li></ul></ul></ul><ul><ul><ul><li>EKG </li></ul></ul></ul><ul><ul><ul><li>Monitoring adverse events </li></ul></ul></ul><ul><ul><li>Supporting pharmacology/toxicology data in animal models </li></ul></ul><ul><li>Efficacy </li></ul><ul><ul><li>Immunogenicity testing in volunteers includes: </li></ul></ul><ul><ul><ul><li>Measurement of humoral immune responses (specific antibody measurement) </li></ul></ul></ul><ul><ul><ul><li>Cell-mediated immune responses (T cell proliferation, cytotoxicity assay) </li></ul></ul></ul><ul><ul><li>Challenge data from animal models to support efficacy </li></ul></ul>
  16. 16. Regulations <ul><li>Good Clinical Practices (GCP) </li></ul><ul><ul><li>GCP is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects. </li></ul></ul><ul><ul><li>Clinical trials must be conducted following GCPs. </li></ul></ul><ul><li>Good Laboratory Practices (GLP) </li></ul><ul><ul><li>Govern protocol and conduct of nonclinical (animal) studies. </li></ul></ul><ul><li>Current Good Manufacturing Practices (CGMP) </li></ul><ul><ul><li>Requires manufacturers to document production, inspect and release quality drug products. </li></ul></ul><ul><ul><li>Covers all vaccine manufacturing and post-production (shipping, storage, etc.). </li></ul></ul>
  17. 17. Additional DoD Regulations <ul><li>In addition to all applicable ICH/FDA regulations for human clinical trials, the DoD requires a second level of review and approval for DoD-sponsored research. </li></ul><ul><ul><li>Human Subjects Research Review Board (HSRRB) </li></ul></ul><ul><ul><li>Approval must be obtained prior to initiation of research protocol </li></ul></ul><ul><ul><li>HSRRB policies: </li></ul></ul><ul><ul><ul><li>Format of clinical protocol </li></ul></ul></ul><ul><ul><ul><li>Volunteer database </li></ul></ul></ul><ul><ul><ul><li>Informed consent </li></ul></ul></ul><ul><ul><ul><li>Reporting of adverse events </li></ul></ul></ul><ul><ul><li>13 more required clauses for additional protection of study volunteers </li></ul></ul>
  18. 18. Clinical Trials at DVC <ul><li>DVC outsources conduct of clinical trials to contract research organizations (CROs) </li></ul><ul><ul><li>DVC remains responsible for trial design, oversight and documentation/deliverables </li></ul></ul><ul><li>Clinical trial deliverables </li></ul><ul><ul><li>Investigator’s brochure (IB) and trial protocols </li></ul></ul><ul><ul><li>Final clinical study reports (CSRs) </li></ul></ul><ul><ul><li>IND safety reports at various intervals </li></ul></ul><ul><ul><li>Serious adverse event reporting </li></ul></ul>
  19. 19. Adverse Events <ul><li>An adverse event (AE) is any adverse change in health or side effect that occurs while a subject is taking part in a clinical trial. </li></ul><ul><ul><li>May be related or unrelated to the investigational product. </li></ul></ul><ul><ul><li>AEs happen in every clinical trial. </li></ul></ul><ul><li>A serious adverse event (SAE) is any adverse experience that results in death, is life-threatening or requires hospitalization. </li></ul>
  20. 20. Biologics License Application (BLA) <ul><li>If products are successful in proving safety and efficacy through nonclinical and clinical testing, the Sponsor may apply for FDA licensure through the BLA process. </li></ul><ul><li>DVC received FDA licensure of the first biodefense product in 2005 </li></ul><ul><ul><li>Vaccinia Immune Globulin, a smallpox vaccine antiserum </li></ul></ul><ul><ul><li>Many biopharmaceutical companies never reach this milestone </li></ul></ul>
  21. 21. Launch and Post-Marketing <ul><li>Post-licensure activities may be required by licensing authority (FDA) </li></ul><ul><ul><li>Further safety database </li></ul></ul><ul><ul><li>Special populations (pediatric, elderly, high-risk) </li></ul></ul><ul><ul><li>Pregnancy registry </li></ul></ul>
  22. 22. 2005: DVC receives first-ever FDA licensure for a biodefense product (VIGIV) 2008: DVC and Quintiles win $32M NIAID Phase 1 clinical trial unit contract DVC biodefense milestone Emerging diseases / services milestone 2003-2009: DVC completes six Phase 1 clinical trials for biological and chemical defense countermeasures 2008: DoD plague RAD allocates all future DoD plague vaccine funding to existing DVC contract 2005-ongoing: DVC initiates and manages Phase 2 clinical trials for botulinum neurotoxin and plague vaccines 2006: DVC and Baxter win $242 M HHS award to develop seasonal and pandemic influenza vaccines DVC Milestones Throughout the Product Development Life Cycle
  23. 23. Vaccine 101 Vaccine Manufacturing
  24. 24. Manufacturing: Getting There <ul><li>Research and development </li></ul><ul><ul><li>Provides material for early studies </li></ul></ul><ul><li>Process development </li></ul><ul><ul><li>Takes R&D process and develops a process for manufacturing </li></ul></ul><ul><ul><li>This is a complex endeavor, with many variables (i.e., opportunities for things to go wrong) </li></ul></ul><ul><li>Manufacturing </li></ul><ul><ul><li>Executes the process in an environment compliant with Current Good Manufacturing Practices (CGMPs), as required by FDA </li></ul></ul>
  25. 25. Product and Manufacturing Stages <ul><li>Product stages </li></ul><ul><ul><li>Cell banks </li></ul></ul><ul><ul><li>Bulk drug substance </li></ul></ul><ul><ul><li>Final drug product </li></ul></ul><ul><li>Stages of manufacturing </li></ul><ul><ul><li>Banking </li></ul></ul><ul><ul><li>Production </li></ul></ul><ul><ul><li>Recovery </li></ul></ul><ul><ul><li>Purification </li></ul></ul><ul><ul><li>Formulation and filling </li></ul></ul><ul><ul><li>Finish </li></ul></ul>Testing at all stages to demonstrate control Nunc TM cell factory
  26. 26. A Few More Notes on Manufacturing <ul><li>Manufacturing biopharmaceuticals is time-intensive. </li></ul><ul><ul><li>Facility: 2 to 3 years </li></ul></ul><ul><ul><li>Equipment: 6 to 12 months </li></ul></ul><ul><li>Manufacturing is expensive. </li></ul><ul><li>Changes in the process have huge cost/schedule implications. </li></ul><ul><ul><li>Careful subcontractor management and long-term relationships required for success. </li></ul></ul><ul><li>A manufacturing facility is part of the license requirement. </li></ul>
  27. 27. Vaccine 101 Putting Things Together
  28. 28. Regulatory Affairs <ul><li>Guides all DVC programs in areas of regulatory strategy and compliance. </li></ul><ul><ul><li>Recommends testing requirements at various stages of manufacturing (in-process, lot release, characterization, etc.). </li></ul></ul><ul><ul><li>Reviews plans for correlates of protective immunity. </li></ul></ul><ul><ul><li>Provides regulatory review and support strategies during product development. </li></ul></ul><ul><li>Regulatory strategies utilized by DVC include: </li></ul><ul><ul><li>Accelerated Approval </li></ul></ul><ul><ul><li>Fast Track Designation </li></ul></ul><ul><ul><ul><li>DVC maintains a 100% success rate for receiving Fast Track designation (four products) as compared to a 63% industry standard.* </li></ul></ul></ul><ul><ul><li>Orphan Drug Program </li></ul></ul><ul><ul><li>Priority Review </li></ul></ul><ul><ul><li>Rolling Submission </li></ul></ul><ul><ul><li>Emergency Use </li></ul></ul>*Source:
  29. 29. Regulatory Affairs (continued) <ul><li>Acts as the DVC representative in interactions with the U.S. FDA and foreign regulatory agencies. </li></ul><ul><ul><li>Prepares and assembles all required regulatory submissions, including Investigational New Drug and Biologics License Applications. </li></ul></ul><ul><li>Reviews all publicity materials (press releases, brochures, Web pages, etc.) to ensure that no unproven marketing claims are made regarding FDA-regulated products. </li></ul>
  30. 30. FDA Animal Rule <ul><li>Regulatory Affairs oversees DVC’s use of the FDA Animal Rule. </li></ul><ul><ul><li>Allows for FDA licensure of vaccines and other products in which efficacy testing in humans is unethical </li></ul></ul><ul><ul><li>At least two species (nonhuman primates and rodents) </li></ul></ul><ul><ul><li>Must understand pathophysiology of the disease </li></ul></ul><ul><ul><li>Well-controlled animal studies will provide data that are likely to predict a benefit in humans </li></ul></ul><ul><li>The Animal Rule is NOT a shortcut to licensure. </li></ul><ul><ul><li>So far, no vaccines have been licensed using the Animal Rule. </li></ul></ul>DVC is an industry leader in Animal Rule development.
  31. 31. Quality Assurance <ul><li>To ensure impartiality, the Quality Management Office (QMO) is independent of the product teams and functional departments. </li></ul><ul><li>The QMO performs audits, conducts quality reviews and initiates investigations to demonstrate that both DVC and its subcontractors are operating in a state-of-control to ensure compliance with Section 501(a)(2)(B) of the Food, Drug and Cosmetic Act . </li></ul><ul><ul><li>Compliance failures could affect the quality of the product, which could lead to death of the volunteer/patient. </li></ul></ul><ul><ul><li>Compliance failures could lead to lost credibility with the FDA and enforcement actions including product seizure, injunctions, criminal fines and imprisonment. </li></ul></ul><ul><li>Administers (federally required) Standard Operating Procedures (SOPs) and SOP training, and Document Control. </li></ul>
  32. 32. Quality Assurance (continued) <ul><li>QA is comprised of two arms: </li></ul><ul><ul><li>Product Quality Assurance (PQA) </li></ul></ul><ul><ul><ul><li>Ensures compliance of manufacturing, testing and storage subcontractors </li></ul></ul></ul><ul><ul><li>Clinical Quality Assurance (CQA) </li></ul></ul><ul><ul><ul><li>Primary responsibilities are to manage safety risk to clinical study volunteers and to assess data integrity </li></ul></ul></ul><ul><li>QA also monitors data integrity and oversees validation of computer systems. </li></ul>
  33. 33. Program Management <ul><li>Program managers of biopharmaceutical development programs must balance: </li></ul><ul><ul><li>Cost </li></ul></ul><ul><ul><li>Schedule </li></ul></ul><ul><ul><li>Risk </li></ul></ul><ul><ul><li>Technical requirements </li></ul></ul><ul><ul><li>Product life cycle </li></ul></ul><ul><ul><li>External influences (changes in regulatory guidance, client funding profiles, etc.) </li></ul></ul><ul><li>Good program management is often at odds with “good science.” </li></ul><ul><ul><li>Must curtail the “what-ifs” and stop at “good enough” </li></ul></ul>
  34. 34. Biosafety <ul><li>Biological surety </li></ul><ul><ul><li>New and evolving DoD requirements for personnel, subcontractors working with select agents </li></ul></ul><ul><ul><li>Narrows field of prospective subcontractors even further </li></ul></ul><ul><li>Shipping </li></ul><ul><ul><li>Shipping biological agents is complicated and highly regulated (much more so internationally) </li></ul></ul><ul><ul><li>Temperature control is crucial for vaccines (for now) </li></ul></ul><ul><ul><li>Test shipments must be conducted with vendors before actual product is put at risk </li></ul></ul>DVC is a pioneer in this new requirement.
  35. 35. Vaccine 101 Biodefense and Vaccines
  36. 36. Priority Pathogens <ul><li>Centers for Disease Control and Prevention (CDC) identifies three threat agent categories. </li></ul><ul><li>Category A* – The most severe threats, Category A agents pose a risk to national security and can be transmitted person-to-person or easily disseminated. These agents result in high mortality rates and would be most likely to cause public panic and social disruption: </li></ul><ul><ul><li>Anthrax </li></ul></ul><ul><ul><li>Botulinum neurotoxin </li></ul></ul><ul><ul><li>Plague </li></ul></ul><ul><ul><li>Smallpox </li></ul></ul><ul><ul><li>Tularemia </li></ul></ul><ul><ul><li>Viral hemorrhagic fevers </li></ul></ul><ul><ul><ul><li>Filoviruses (e.g., Ebola, Marburg) </li></ul></ul></ul><ul><ul><ul><li>Arenaviruses (e.g., Lassa) </li></ul></ul></ul>DVC has experience with nearly all of these. *Source:
  37. 37. Questions?