The document outlines the 5 step process for drug approval by the FDA: 1) discovery and development, 2) preclinical research, 3) clinical research consisting of 4 phases, 4) FDA review of the new drug application, and 5) post-marketing safety monitoring. It describes each step in detail. Upcoming trends in drug development include specialty drugs, gene therapy, opioids, ophthalmology drugs, and biosimilars. Questions are welcome.

1. The Prescription Drug
Pipeline
KRISTIN O’DONOVAN

2. M&S Projects:
 North Carolina:
 QUR
 PDP – monthly and annual CPT updates
 Radiopharmaceuticals
 Oregon:
 MCO/FFS PDL Audit
 Louisiana:
 NADAC vs. AAC Rate Comparison
 Training:
 Book Review
 Final Presentation (Pipeline & Drug Information)
 Training Survey Results

3. Overview
 FDA drug approval process
 Types of drug approvals
 Importance of drug development
 Up-and-coming trends
 Drug information resources

4. FDA Drug
Approval Process

5. Drug Development Process
Discovery &
Development
1
Preclinical Research
2
Clinical Research
(Phase 1 – 3)
3
FDA Review
4
FDA Post-
Marketing Safety
Monitoring
(Phase 4)
5

6. Step 1: Discovery & Development
Discovery
 New drugs can be discovered by:
 Tests of molecular compounds against diseases
 New technologies (i.e. targeting or gene therapy)
 Unexpected effects of existing treatments
 New disease process insights leading to drug design
 Thousands of compounds may be discovered, but after early testing a small number
move on to development

7. Step 1: Discovery & Development
Development
 Further experiments are conducted to gather information on:
 Absorption, distribution, metabolism, excretion (ADME)
 Benefits and mechanism of action (MOA)
 Dosage
 Side effects and toxicities
 Effects in different groups
 Drug interactions
 Efficacy compared to similar drugs

8. Step 2: Preclinical Research
 Occurs before drug can be tested in humans
 Objective: to determine drug’s potential to cause serious harm
 Two types:
 In vitro
 In vivo
 FDA requires good laboratory practices (GLP’S)
 Usually aren’t large studies
 Must provide detailed information on dosing and toxicity
 Findings determine whether drug can be tested in people

9. Step 3: Clinical Research
 Refers to studies done in people
 Researchers design each phase of the study based on what they want to discover
 Clinical Research Consists of:
 Trial design
 Phase studies
 Investigational New Drug (IND) process
 Asking for FDA assistance
 FDA IND Review
 Approval

10. Designing Clinical Trials
 Clinical trials are designed to answer specific questions related to the products
 Follow a protocol designed by researchers/manufacturers
 Before beginning trial, prior information about drug is reviewed
 Decisions to be made:
 Selection criteria
 Study size
 Study timeline
 Controls and bias limitations
 Administration/dosage
 Assessments and data collection
 Data analysis
Step 3: Clinical Research (continued)

11. Clinical Research Phase Studies:
 Typical series follows early, small-scale, Phase 1 to late, large-scale Phase 3
Step 3: Clinical Research (continued)
Phase 1: Safety and
Dosage
•20 to 100 Healthy
Volunteers
•Several months
70%
Phase 2: Efficacy and
Side Effects
•Up to several
hundred people
with
disease/condition
•Several months to
2 years
33%
Phase 3: Efficacy and
Adverse Effect
Monitoring
•300 to 3,000
volunteers who
have the disease or
condition
•1 to 4 years
25 – 30%
Phase 4: Post-Market
Safety and Efficacy
•Several thousand
volunteers who
have the disease or
condition

12. The Investigational New Drug Process:
 Drug developers (sponsors) must submit IND before beginning clinical research
 Included in the IND application:
 Animal study data and toxicity
 Manufacturing information
 Clinical protocols (phase study plans)
 Data from prior human research (if any)
 Investigator information
Step 3: Clinical Research (continued)

13. Asking for FDA Assistance:
 Developers are allowed to ask the FDA for help at any time:
 Pre-IND application to review document guidance
 After Phase 2 to gain advice on design of large Phase 3 studies
 Any time to obtain IND application assessment
 Developers not required to take FDA’s suggestions as long as federal standards
are met
Step 3: Clinical Research (continued)

14. FDA IND Review Team:
 Team consists of specialists from different fields, each with different responsibilities
 Project manager: Primary contact, coordinates team’s activities throughout review
 Medical officer: Reviews all clinical study data and information
 Statistician: Interprets trial design and data, helps medical officer evaluate protocols
 Pharmacologist: Reviews preclinical studies
 Pharmakineticist: Focuses on ADME processes, interprets blood-level data
 Chemist: evaluates drug’s chemical compounds for stability, purity, quality, etc.
 Microbiologist: Assesses response across different classes of microbes for antimicrobial
products
Step 3: Clinical Research (continued)

15. Approval:
 Review team has 30 days to review original IND submission
 Responds in 1 of 2 ways:
 Approval to begin clinical trials
 Clinical hold to delay or stop investigation for various reasons:
 Unreasonable or significant risk to participants
 Investigators not qualified
 Misleading materials for volunteer participants
 Not enough information about trial risks
 Clinical hold is rare, approval with comments more common
 Investigator responsible for updating review team
Step 3: Clinical Research (continued)

16. Step 4: FDA Review
 Once clinical and preclinical research supports drug safety and efficacy, developer can
apply to market the drug
 New Drug Application (NDA):
 Everything from preclinical data to Phase 3 trial data
 Proposed labeling
 Safety updates
 Abuse information
 Patent information
 Data from international studies
 IRB compliance information
 Directions for use

17. FDA Review:
 Once NDA is received, FDA will determine whether it is complete:
 Incomplete: Refuse to file
 Complete: Review for approval
 The review team has 6 – 10 months to decide on approval
 Each team member reviews his/her section of application
 FDA inspectors visit study sites and look for evidence of data fabrication, withholding, or
manipulation
 Project manager assembles all components into “action package”, team makes a
recommendation, and senior FDA official makes decision
Step 4: FDA Review (continued)

18. FDA Approval and Advisory Committees:
 Approval:
 Once drug is approved, FDA and manufacturer develop prescribing information (labeling)
 FDA can require developer to address questions or perform additional studies:
 Developer can decide whether or not to continue development
 Developer can formally appeal FDA decision
 Advisory committees:
 If safety and efficacy questions arise, FDA can organize Advisory Committee meeting of
independent experts (including patient representative) for advice and public comment
Step 4: FDA Review (continued)

19. Step 5: FDA Post-Marketing Safety
Monitoring
 FDA continues to monitor drugs and reviews reports of problems including:
 Supplemental applications (for significant changes)
 INDs for marketed drugs (further development)
 Manufacturer inspections
 Drug advertising
 Generic drugs (ANDA)
 Reporting problems (MedWatch and MedSun)
 Active surveillance
 Can decide to add cautions or measures for more serious issues

21. Types of Drug
Approvals

22. Application Types
- study of previously undiscovered compound
- Further development of marketed drug (indication, strength, form)
Investigational New Drug
(IND)
- marketing of studied new compound
- Supplemental applications for changes to NDA (dosage, labeling)
New Drug Application
(NDA)
- generic drug product
Abbreviated New Drug
Application (ANDA)
- drugs available without prescription
Over-the-Counter (OTC)
- monoclonal antibodies, cytokines, growth factors,
immunomodulators, thrombolytics, and proteins
Biologic License
Application (BLA)

23. Importance of Drug Development:
 Advancements in care
 Market competition and cost insights
 Therapeutic area insights
 Insights into company success
 Money (for further research)

24. Up-and-Coming

25. 2018 Pipeline Trends
 Specialty drugs
 Gene therapy
 Opioids
 Ophthalmology
 Biosimilars

27. Questions?

28. Thank you!

29. Sources:
 https://www.fda.gov/ForPatients/Approvals/Drugs/default.htm
 https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelope
dandApproved/ApprovalApplications/default.htm
 https://www.biopharmadive.com/news/biopharma-trends-to-watch-in-
2018/513714/