Terri Specht

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Terri Specht

• Summer Intern 2004
• Center for Veterinary Medicine
• US Food and Drug Administration
• June 7-Aug. 13

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FDAs Mission Statement

• The FDA is responsible for protecting the public
  health by assuring the safety, efficacy, and
  security of human and veterinary drugs,
  biological products, medical devices, our
  nations food supply, cosmetics, and products
  that emit radiation. The FDA is also responsible
  for advancing the public health by helping to
  speed innovations that make medicines and foods
  more effective, safer, and more affordable and
  helping the public get the accurate,
  science-based information they need to use
  medicines and foods to improve their health.

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CVMs Mission Statement

• The Center for Veterinary Medicine is a consumer
  protection organization. We foster public and
  animal health by approving safe and effective
  products for animals and by enforcing other
  applicable provisions of the Federal Food, Drug,
  and Cosmetic Act and other authorities.

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The People

• My mentor Michele McGuinness, PhD
• My officemate Christin Janczak
• Director of Division of Production Drugs Woodrow
  Knight, PhD
• Swine and Poultry Drugs Review Team
• Team Leader Charles Andres, PhD
• Michele McGuinness, PhD
• Tom Modric, DVM, PhD
• Pat Ryan, Consumer Safety Officer
• Tim Schell, PhD
• Administrative
• Traci Bailey
• Lesley Groves

• Ruminant Drugs Review Team
• Team Leader Eric Dubbin, DVM
• Amey Adams, PhD
• Dan Benz, PhD
• Harlan Howard, PhD
• Suzanne Sechen, PhD

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Governmental Structure
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CVMs Structure
Center Level Center for Veterinary
Medicine (CVM)
Office Level
Office of Management (OM)
Office of Research (OR)
Office of Surveillance and Compliance (OSC)
Office of New Animal Drug Evaluation (ONADE)
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About CVM

• Regulates
• Animal Drugs
• Animal Feed
• Medical Devices post market requirements only
• USDA regulates vaccines
• Animal Species Involved
• Cattle, Swine, Chickens, Turkeys, Horses, Cats,
  Dogs
• Minor Species such as Fish, Sheep, Goats, etc

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About CVM cont.

• Foster public health by approving safe and
  effective products for animals
• Regulatory authority under the Federal Food,
  Drug, and Cosmetic Act and Title 21 of the Code
  of Federal Regulation
• Safety of human and animal food supply
• Animal Health

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Internship Tasks

• Learn about Genomics, Proteomics, and
  Pharmacogenomics
• Attend meetings
• Animal Biotechnology Working Group and GP
  subcommittee
• Division and Team meetings
• Agency genomics and proteomics interest group
• FDA Workshop on Pharmacogenomics
• Literature searches, notebook, and electronic
  reference library
• Interviews of CVM scientists
• ONADE Review scientists with PG data in
  applications
• Office of Research scientists using GP
  technology
• Summarize CVM activities in GP

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Importance of Project

• Multiple government agencies are working
  together, along with industrial partners
• To prepare for the impact of new GP technologies
  on their regulatory functions
• To standardize the technology
• Agency level directive for each Center in FDA to
  explore the effects of the emerging technologies
• Understanding the potential impact of GP on the
  animal drug approval process and other regulatory
  functions at CVM

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What is Genomics and Proteomics?

• Genomics The study of how the genome,
  mutations, or alternate alleles of an individual,
  a population, or a species may affect growth and
  development, health, disease status, or response
  to a drug.
• Proteomics The set of expressed proteins
  affecting the current status of an individual, or
  a characteristic profile of proteins regulating a
  condition or response in an individual or
  species.
• Systems biology Integrated approach to
  understanding the physiological interactions of
  the whole organism, using GP technology.

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What is Pharmacogenomics?

• The pharmacologically-responsive genes of the
  individual drug recipient, or the gene
  interactions and metabolic pathways involved in
  the drug response
• The genes or sets of genes involved in the
  response to the drug, described in general terms
  for an entire population
• Discovery-type research and new biomarkers
• drug design
• Selection criteria for participants in clinical
  trials
• evaluation of effectiveness, safety, toxicity
• mechanism of action

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What is Pharmacogenetics?

• The effect of an individuals specific genotype
  on the effectiveness, safety, and metabolism of
  the drug, or on the drug mechanism of action
• An individual or a defined population, such as a
  family, ethnic group, or local population who may
  have an alternate allele or mutation for a
  drug-responsive protein
• Often included under the wider term of
  pharmacogenomics

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Ethical Challenges for GP Tests

• Tests reveal personal and sensitive information
  about an individual
• The information may be formerly unknown to the
  individual before testing, such as the potential
  for cancer or a genetic disease
• Patient confidentiality for results from genetic
  tests is of major concern worldwide
• DNA and tissue samples are stable and can be
  stored for many years, and may later be used for
  other purposes not originally intended
• Patient consent forms for clinical trials should
  be designed to include possible future uses of
  samples

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What is a Biomarker?

• Biomarker
• A characteristic that is objectively measured
  and evaluated as an indicator of normal
  biological processes, pathogenic processes, or
  pharmacologic responses to a therapeutic
  intervention.
• New types of PG biomarkers
• Gene mutation or alternate allele
• Characteristic cluster of genes from MA data
• Profile of plasma proteins

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Development of New PG Biomarkers

• MDR1 (Multidrug Resistance Gene)
• Responsible for making P-glycoprotein
• Functions as a drug pump within cells
• Plays a very important role in the blood-brain
  barrier
• 3 variations of genetics
• Wt/Wt normal, or those carrying the mutation
  (Wt/-) or (-/-)
• Deletion mutation results in a frame shift for
  protein translation, inserting a premature stop
  codon and creating a mutant protein.
• Mutant protein is a non-functional, truncated
  P-glycoprotein
• Even one copy of the mutant allele causes drug
  sensitivity
• Collies and other herding dogs carry the MDR1
  mutation
• Causes sensitivity to Ivermectin and other
  classes of drugs
• Excess drug levels at the brain lead to
  neurological effects
• Testing may now be done to determine genetic
  status and to modify the drug treatment plan

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Importance of New technology

• Humans or animals taking a drug may have an
  adverse affect, such that the drug may be either
  ineffective or toxic
• New genetic tests may be used before treatment to
  eliminate non-responders or those with increased
  chance of SAE
• Concept of personalized medicine
• Develop safer or more effective drugs through
  custom design or targeting of a cellular pathway
• Allow doctors to tailor a drug specifically for
  an individual or their medical condition, based
  on genetic information (cancer therapy)
• PG may help prevent SAE by identifying gene
  pathways or alleles involved in drug response or
  metabolism

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Abilities Learned

• Learned about FDA/CVM
• Role in government
• Role in public safety
• Role in veterinary medicine
• Learned about the New Animal Drug Evaluation
  Process
• Learned about many new technological advances

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Abilities Learned cont

• Career opportunities
• Computer skills
• Communication skills
• Research skills
• Teamwork skills

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Courses taken at OSU

• Biochemistry 511
• Molecular Genetics 500

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Acknowledgements

• My Mentor Dr. Michele McGuinness, PhD
• My officemate Christin Janczak
• Division of Production Drugs
• OR Scientists
• Dr. Mike Scott, PhD
• Dr. Haile Yancy, PhD
• ONADE Reviewers
• Dr. Lisa Troutman, DVM

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QUESTIONS??