Presentation on drug development and the 2018 pipeline

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/