U.S. Regulation of Drug Development and the Role of The Information Professional - PowerPoint PPT Presentation

Loading...

PPT – U.S. Regulation of Drug Development and the Role of The Information Professional PowerPoint presentation | free to download - id: 82514-ZDc1Z



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

U.S. Regulation of Drug Development and the Role of The Information Professional

Description:

Pre-Clinical. Clinical Testing. Marketing. IND. NDA. Lab. Market. SNDAs - 4 ... Type B Meeting: (1) pre-IND meetings (21 CFR 312.82), (2) certain end of Phase ... – PowerPoint PPT presentation

Number of Views:113
Avg rating:3.0/5.0
Slides: 51
Provided by: informat555
Learn more at: http://units.sla.org
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: U.S. Regulation of Drug Development and the Role of The Information Professional


1
U.S. Regulation of Drug Development and the
Role of The Information Professional
  • Alberto Grignolo, Ph.D.
  • Corporate VP and General Manager
  • PAREXEL Consulting
  • Alberto.Grignolo_at_PAREXEL.com

2
Think about it . . .
If you had to sign a letter authorizing the
availability of a new medicine to 250 million
Americans -- What kind of information (and how
much of it) would you want to have about the
drug?
3
What is Drug Development?
Development
Commercial
Discovery
Lab
Market
Basic Research
Pre-Clinical
Clinical Testing
Marketing
Product Launch
Sales
IND
NDA
SNDAs
4
The Purpose of Drug Development
P.I.
From Lab to Label The Outcome of Drug
Development is the Negotiated Language of the
Prescribing Information
5
What Disciplines Are Involved in Drug Development?
  • Drug Discovery Scientists
  • Pharmacologists
  • Toxicologists
  • Microbiologists
  • Biopharmaceuticists
  • Chemists (Process, Engineers, Organic,
    Analytical)
  • Clinicians
  • Biostatisticians
  • Information Professionals
  • Regulatory Affairs
  • Project Management
  • Financial Management
  • Executive Management
  • Regulatory Agencies
  • Volunteers
  • Patients
  • Advocacy Groups
  • Investors
  • The Media

6
Drug Development Begins with the End in Mind
Product Labeling
Development
Labeling
Lit Searches
Description Indication Precautions Warnings Contra
indications Dosage / Administration How Supplied
Pharmacology Toxicology Pharmacokinetics Drug
Metabolism Clinical Efficacy Clinical Safety
New Drug
VISION
7
Role of Regulatory Affairs in the Drug
Development Universe
FDA
Senior Management
Project Management
Regulatory Affairs
Biopharmaceutics
Clinical
Biostatistics
Pharmacology
Info Professionals
Toxicology
Basic Research
Regulatory Affairs is the Companys Ambassador to
FDA
8
The Regulation of Drug Development
  • In the United States, the entire process of drug
    development and commercialization is regulated
  • (except the price of the drug, but . . . just
    wait)

9
Functions of Regulation
  • To protect patients from harmful medical
    products
  • To facilitate the availability of beneficial
    medical products to patients

10
The legal framework for drug regulation in the
United States
LAWS
CONGRESS
REGULATIONS
FDA
GUIDELINES
INDUSTRY
11
Definitions
  • Laws legislation passed by the United States
    Congress and signed by the President
  • Examples
  • FDCA (Food Drug and Cosmetic Act, 1938)
  • PDUFA (Prescription Drugs User Fee Act, 1992,
    1997, 2002)
  • FDAMA (FDA Modernization Act, 1997)

12
NDA (NME) Approval Time Has Decreased Since PDUFA
1992
Source FDA
13
Definitions
  • Regulations rules issues by FDA consistently
    with Laws, published in the Federal Register and
    contained in Code of Federal Regulations (CFR)
  • Examples
  • INDs 21 CFR 312
  • NDAs 21 CFR 314
  • IRB and Informed Consent (21 CFR 50 and 56)

14
Definitions
  • Guidelines informal documents issued by FDA to
    clarify requirements often specific to
    therapeutic areas or technical disciplines
  • Examples
  • Guidelines on Drug Stability Testing
  • Guideline on How to Develop Anti-Inflammatory
    Drugs

15
The Difference
(Credit Steve Wilson, FDA)
GUIDELINES
REGULATIONS
16
Proactive Information Needs
  • New regulations (Federal Register)
  • Proposed, draft and final guidances (Federal
    Register, Whats New in CDER and CBER)
  • Advisory Committee meeting announcements (Federal
    Register)
  • Industry news (journals, newspapers)
  • Drug development process research (Tufts CSDD,
    IoM, etc.)

17
Fundamental Principle
  • No drug can be marketed in the United States
    until substantial evidence of its quality,
    safety and effectiveness has been provided to
    FDAs satisfaction.

18
Some Definitions
  • Quality the characteristics of the drug,
    including its manufacturing
  • Safety the relative risk of harm
  • Effectiveness the benefit provided to the
    patient
  • Risk/Benefit Ratio the degree to which risk is
    acceptable, given the amount of benefit provided
    to the patient

19
Substantial Evidence What Is It ?
  • Quality tight procedures, reproducibility of
    manufacturing, specifications, pass FDA
    inspection
  • Safety low risk demonstrated in tests on animals
    and patients
  • Effectiveness benefit demonstrated in tests in
    animals and patients

20
Substantial Evidence How Do We Get It ?
  • Test the product in animals and patients see if
    it works and if it does any harm
  • Use controlled conditions of testing to
    eliminate the possibility that test results are
    wrong
  • Apply rigorous scientific, medical and regulatory
    standards throughout

21
FDAs Satisfaction How Do We Know What FDA
Wants ?
  • Regulations state what must be done, in general
  • Guidelines provide advice on what is required for
    specific products
  • Meetings very specific technical discussions and
    negotiations on individual products
  • Correspondence technical negotiations on very
    fine points

22
Doing Clinical Trials in the U.S.
  • The Role of the IND

23
The Investigational New Drug (IND) Application as
the Platform for Drug Development
Development
Commercial
Discovery
Lab
Market
Basic Research
Pre-Clinical
Clinical Testing
Marketing
Product Launch
Sales
IND
NDA
SNDAs
STRATEGY
24
Information Needs for Regulatory Strategy
  • Identify similar drugs/treatments for specific
    indications
  • Obtain regulatory approval documents (EPARs, FDA
    Approval Packages/SBAs)
  • Identify all relevant guidance documents, both
    regulatory (EMEA, FDA) and medical (ASCO, etc.)

25
Information Needs for Clinical Development
Strategy
  • Define market size for indication, including by
    class of drugs
  • Incidence prevalence of indications in various
    countries to develop strategy for selection of
    patient groups and trial locations re
    proof-of-concept studies
  • Identify competing products in development
    (pipeline)
  • Literature search to identify pivotal clinical
    trials re standard trial protocol examples

26
Why do we need an IND?
An IND is required in order to conduct clinical
trials in the United States
  • IND (Investigational New Drug Application) is an
    exemption from the law that prohibits interstate
    shipment of unapproved drugs

27
IND Submitted
Chem Mfg
Animal Studies
Clinical Studies
Time
28
IND Principal Goals
Clinical Protocol Subject must not be exposed to
unnecessary risks
SAFETY
Preclinical/Other Data Adequate evidence that
the drug is reasonably safe for
administration to humans
CMC CMC procedures ensure that the drug is
adequately reproducible and stable
29
Information Needs for INDs
  • Safety, pharmacokinetics, and toxicity of study
    drug or drugs similar to study drug in animals
    and humans to provide evidence that drug is
    reasonably safe for administration to humans
  • Safety and efficacy of a class of drugs via a
    specific administration (IV, oral, etc.) in
    specific indications to justify a protocol dose
    selection

30
The Phases of Clinical Development
Phase 1 Phase 2
  • 20-80 Subjects
  • Patients or Normal Volunteers
  • Metabolism/Pharmacologic Actions
  • Side Effects with Increasing Dose
  • Early Efficacy Information
  • ADME
  • Several Hundred Subjects
  • Patients with Disease Under Study
  • Well Controlled Studies
  • Efficacy and Safety

Phase 3 Phase 4
  • Hundreds to Thousands of Subjects
  • Patients with Disease Under Study
  • Well Controlled Studies
  • Efficacy and Safety
  • Post-NDA Approval
  • Epidemiology Studies
  • Marketing Studies

31
The New Drug Application (NDA)
  • The vehicle through which sponsors formally
    request that the FDA approve a new pharmaceutical
    for marketing in the US, on the basis of
    demonstrated quality, safety and efficacy.

32
The Common Technical Document Format for the NDA
Not Part of the CTD
Module 1 Regional Administrative Information 1.1
Submission ToC

CTD Table of Contents 2.1 CTD Introduction 2.2
Module 2
Nonclinical Overview 2.4
Clinical Overview 2.5
Quality Overall Summary 2.3
CTD
Nonclinical Written and Tabulated Summaries 2.6
Clinical Summary 2.7
Module 5 Clinical Study Reports 5 5.1 ToC
Module 3 Quality 3 3.1 ToC
Module 4 Nonclinical Study Reports 4 4.1 ToC
33
Information Needs for NDA Submission and Beyond
  • Literature search for safety and efficacy in
    humans of study drug in comparable indications,
    administrations, or dosages clinical trials,
    review articles, case studies, etc.
  • Literature search on all published studies for
    specific drug and indication for 505(b)(2)
    submissions (paper NDAs)
  • After NDA approval, the obligation to report drug
    safety information from patients and/or
    additional studies grows exponentially and is a
    significant information management challenge
    (pharmacovigilance)

34
  • Interactions with FDA

35
Meetings with FDA During Early Drug Development
Can Shorten NDA Review and Approval Time
NDA Review Time (mos)
Source DiMasi and Manocchia, DIA Journal 1997
36
Meeting Regularly with FDA is a Success Factor in
Drug Development
  • Maintain ongoing relationship
  • Avoid misunderstandings
  • Communicate new data
  • Highlight and jointly resolve problems before
    they become too large
  • Anticipate difficulties
  • Monitor changes in FDA attitude or expectations
    of data
  • Avoid surprising each other
  • Accelerate development process
  • FDA Center for Drugs holds gt1000 industry
    meetings every year

37
Regulatory Approval is Earned Gradually, Not in a
Final and Glorious Battle with FDA
  • Planning for the Target Labeling early in
    development
  • Thorough development vision and plans
  • Ongoing communication with FDA Build Trust
  • Data-driven development plan revisions
  • Strong project management on both sides
  • Learn from mistakes and take timely corrective
    actions in agreement with FDA

38
Key Ingredients of Successful Meetings
Information Professionals
39
Success Factor No. 1 Science and Medicine
  • FDA decision-making is driven by data
  • FDA relies on internal reviewers and external
    experts to review data and make decisions
  • FDA decisions can change based on changes in
    science, medical knowledge and medical practice
  • If no data, then no positive FDA decision
  • Good science, good medicine and good study
    designs are keys to success

40
Success Factor No. 2 Regulatory Knowledge
  • Company representatives must know the rules
    (regulations, guidelines)
  • Regulatory precedents (previous FDA decisions on
    similar issues) are important
  • It is sometimes possible to push the FDA into a
    dialogue (e.g. post-approval commitments generic
    biologics)
  • Being well-prepared is key

41
Success Factor No. 3 Meeting Process Management
  • FDA meetings must be planned and managed in a
    very specific way
  • There is a defined process for FDA meetings
  • Preparation and documentation are essential
  • Rehearsals are important for the theater and
    they are important for FDA meetings too !

42
FDA Meetings During Drug Development
Pre-IND
EOPII
Pre-NDA
AdComm
Label
Development
Commercial
Discovery
Lab
Market
Basic Research
Pre-Clinical
Clinical Testing
Marketing
Product Launch
Sales
IND
NDA
SNDAs
43
Types of FDA Meetings
TYPE PURPOSE
Pre-IND Verify acceptability
End of Phase I (rare) Confirm early safety
End of Phase II Confirm early efficacy agree Phase III
Pre-NDA Outline NDA approach
Ad-hoc Technical Meetings CMC, Tox, Clinical issues
Advisory Committee Meetings Address medical establishment
Teleconferences Ad hoc
Labeling Meeting Negotiate final labeling
44
FDA Has Provided Guidance for Industry Meetings
  • Guidance for Industry Formal Meetings With
    Sponsors and Applicants for PDUFA Products
  • http//www.fda.gov/cder/guidance/2125fnl.pdf
  • Type A Meetingimmediately necessary for an
    otherwise stalled drug development program to
    proceed (i.e., a critical path meeting). Type A
    meetings generally will be reserved for dispute
    resolution meetings, meetings to discuss clinical
    holds, and special protocol assessment meetings
    that are requested by sponsors after FDA's
    evaluation of protocols in assessment
    letters.Scheduled within 30 days of sponsors
    request.
  • Type B Meeting (1) pre-IND meetings (21 CFR
    312.82), (2) certain end of Phase 1meetings (21
    CFR 312.82), (3) end of Phase 2/pre-Phase 3
    meetings (21 CFR 312.47), and (4) pre-NDA/BLA
    meetings (21 CFR 312.47). Scheduled within 60
    days of sponsors request.
  • Type C Meeting any meeting other than a Type A
    or Type B meeting. Scheduled within 75 days of
    sponsors request.

45
Five Key Success Factors
FACTOR DRIVERS OF SUCCESS
1. Request Letter Clarity about the purpose of the meeting Clarity about the sponsors position and questions Sufficient detail to justify the meeting
2. Information Package Concise, informative, logical Reader-friendly, well-organized Necessary and sufficient background information
3. Preparation Thorough knowledge of the data Anticipation of objections Reasoned alternatives
4. Meeting Management Sponsor Team Leader The right experts in attendance Listen, clarify, respond / propose
5. Negotiation Skills Professionalism Know when to push back, when to concede Time out stop, reflect, return another day
46
Examples of Information Needs re Meetings with
FDA (pre- and post-submission)
  • Background on FDA Reviewers
  • Literature search on specific drug combinations,
    incidence of adverse events, etc. re safety
    concerns
  • Literature search on drug metabolism and toxicity
    to respond to concerns over dosing studies

47
Industry View of FDA
(Dr. Elengold, CBER)
48
FDA View of Pharmaceutical Company
(Dr. Elengold, CBER)
49
Conclusions
  • The FDAs regulation of drug development is
    structured, logical, science-based, data-driven
    and workable
  • In practice, every drug is developed to the beat
    of its own drum, with a skillful mix of science,
    information and diplomatic art
  • Information Professionals play a key role in the
    drug development process and post-approval
    pharmacovigilance obligations by providing access
    to background, data, precedents and adverse event
    tracking to help meet todays regulatory and
    patient care challenges

50
Any Questions?
  • Thank you!
About PowerShow.com