Behind the Scenes of Drug Development

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Behind the Scenes of Drug Development

• Benjamin P. Lewis, PhD, RPh, RAC
• Vice President, Regulatory Affairs
• Prestwick Pharmaceuticals, Inc.

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New Drug Development Process

• History
• Pre-Clinical Research
• Clinical Studies
• Investigational New Drug (IND)
• Phase 1
• Phase 2
• Phase 3
• New Drug Application (NDA)
• Phase 4

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New Drug Development Process History

• FDA100 years (Centennial, 2006)
• 1906The First Federal Drug Law
• Pure Foods Drug Act
• Prohibited misbranded and adulterated foods, and
  drugs being shipped in interstate commerce
• Law required only that drugs meet standards of
  strength and purity

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New Drug Development ProcessHistory

• 1938Food, Drug, and Cosmetic Act
• Mfg required to show that a drug is safe before
  marketing
• Mfg required to submit application to FDA
• Required certain drugs labeled as Rx only

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New Drug Development ProcessHistory

• 1962Kefauver-Harris Amendments to the FDC Act
  (Frances O. Kelsey, MD,PhD Thalidomide)
• In addition to safety, Mfg required to provide
  substantial evidence of effectiveness for the
  products intended use
• Establish rules for investigation of new drugs
  (IND)
• Established requirement for Informed Consent of
  study subjects

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New Drug Development ProcessHistory

• 1983Orphan Drug Act
• Treat rare diseases
• Patient pop. 200,000 or less US
• Patent exclusivity 7 yr
• Tax incentives
• Waiver PDUFA fees
• 1992Prescription Drug User Fee Act (PDUFA)
• Established timeline for FDA review period
• Established fees for NDA

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New Drug Development ProcessStages

• Sponsor (Manufacturer)
• Pre-Clinical Research (Animal)
• Clinical Studies
• Investigational New Drug (IND)
• New Drug Application (NDA)
• FDA
• Who Reviews?
• Establishes PDUFA Time Clock

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Assignment of Drug Review
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New Drug Development ProcessPre-Clinical Research

• Making the drug
• Synthesis and Purification
• Complicated, time-consuming, costly
• Animal Testing
• 2 or more species 1 rodent, 1 non-rodent
• Short-term Testing 2 weeks to 3 months
• Long-term Testing Few weeks several years

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New Drug Development ProcessIND

• Pre-IND Meeting
• Sponsor/FDA Meeting
• Early stage meetings provides opportunity to
  discuss data requirements and resolve any
  scientific issues prior to IND submission

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New Drug Development ProcessIND

• Institutional Review Board (IRB)
• Protection of human subjects in clinical trials
• Written informed consent (signed) before study
  begins

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New Drug Development ProcessIND

• Phase 1 Clinical Studies
• Initial introduction of drug into humans
• Usually conducted in healthy volunteers
• Typical range, 20 to 80 subjects
• Primary purpose is Safety
• Drug side effects, metabolism and excretion

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New Drug Development ProcessIND

• Phase 2 Clinical Studies
• Emphasis is on effectiveness (50-300)
• Obtain preliminary data on whether drug works in
  people with disease or condition
• Controlled trials active drug vs. inactive
  substance (placebo) or different drug
• Safety continues to be evaluated
• Sponsor/FDA Meeting (End of Phase 2)

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New Drug Development ProcessIND

• Phase 3 Clinical Studies
• Phase 3 begins if evidence of effectiveness is
  present in Phase 2 generally 2 adequate
  well-controlled studies
• No. of subjects
• Few hundred to 3000
• Orphan pop. rare disease
• Study different dosages
• Studies gather more information on safety and
  effectiveness

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New Drug Development ProcessNDA

• File New Drug Application
• Formal step that a sponsor takes to ask that the
  FDA consider approving a new drug for marketing
  in the US
• NDA includes all animal and human data and
  analyses of the data, as well as information
  about how the drug behaves in the body and how it
  is manufactured
• FDA Review Period Std 10 mo Fast Track 6 mo
  (priority)

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New Drug Development ProcessNDA

• Bumps in the Road
• If FDA decides that the benefits of a drug
  outweigh the risks, the drug will receive
  approval and can be marketed in the US.
• But, if FDA decides there are problems with the
  NDA or if more information in necessary to make a
  determination, the FDA may decide that a drug is
  approvable or not approvable.

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New Drug Development ProcessNDA

• Phase 4 Studies
• Post-marketing study commitments are studies
  required of or agreed to by a sponsor that are
  conducted after FDA has approved a product for
  marketing. Additional data on a products
  safety, efficacy, or optimal use.

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Conclusion

• Historical Aspects of Law
• Brief Overview of Regulatory Process
• IND
• NDA
• Complex