MPTX 512: Regulation of Pharmaceutical and Biological Products
Instructors: Michael
Hamrell, PhD, President, MORIAH Consultants
Course weight: 3 units
Placement: Latest agenda (may be from previous class)
UPCOMING COURSE SCHEDULE
Introduction
and Purposes:
The pharmaceutical industry is one of the most important drivers in the
health-care economy. Products created by these companies are governed
by complex regulations that vary from one country to another. This course
is designed for students with a strong background in biomedical science
or pharmacy, including students enrolled in the Master’s of Regulatory
Science program. It will provide a learning environment in which students
will analyze the current policies and guidelines under which pharmaceutical
and biological products are developed for human use and regulated while
in commerce. In this course students will explore the trends in policy
development relating to such products. Students will be expected by the
end of the course to know the differences in regulatory requirements for
patented and generic pharmaceuticals, for over-the-counter drugs and biological
products. They will examine critically the newly implemented steps to
harmonize international regulations. Students will expand this new knowledge
by writing a research paper chosen with the course instructors to deal
in depth with an issue of policy or research related to pharmaceutical
or biological products. An emphasis will be placed on relatively informal
lecture formats in which students are encouraged to ask and answer questions
throughout the didactic session.
Course
Objectives:
Students graduating from this course should have a sound understanding
of the drug development process and the role of regulatory bodies in shaping
this path. Thus students should have a solid understanding of the types
of testing that will be required to introduce a new drug onto the market,
and should be able to ensure that the testing is done in the right place
at the right time and is reported appropriately. They should understand
the differences between prescription, OTC and generic drugs, and the implications
of these differences for the introduction, management and surveillance
of the products. The students should understand also the special requirements
to which blood products and biologically-derived products are subject,
and why those requirements have been put in place. Within this new base
of knowledge, students should understand the documentation required to
gain new product approval, to maintain product surveillance and to withdraw
products from the market or change their status.
This syllabus may not reflect recent changes or additions.
Course Outline:
Course content is divided into three-hour blocks with a break between hours. In addition to these classroom blocks students will participate in at least one one-hour computer lab** in which electronic databases will be used for information retrieval and submission.
Classroom:
1. The drug development path
Typical stages in
drug development
Costs and time budgets for new drug development
Drug classes- differences between generic, patented and OTC drugs, as
reflected in US regulations
Differences in European systems
Computer Lab:**
2. Investigational New Drugs: testing to support human trials
Requirements for
IDE application
Identifying promising drugs
Animal trials for toxicity
Animal trials for reproductive and developmental toxicity
3. Bioavailability and Pharmacokinetics
Types of testing
Using animal models to predict human responses
Calculations
Drug interactions and individual variability
4. Investigational New Drugs contd: Planning and implementation of clinical
trials
Stages of clinical
trials
Goals and planning of phase I safety trials
Identifying sites for phase I testing
Considerations when planning testing protocols
Goals and planning of pivotal trials
5. New Drug Applications: chemistry, manufacturing and controls requirements
What is CMC?
Producing products for preclinical and clinical trials
Scaling up for manufacture
Validation
6. New Drug Applications
Regulatory requirements
Compilation and analysis of animal and human data
Budgeting resources for submissions
Building and working in teams to develop submissions
7. Abbreviated New Drug Applications ; Obtaining Formulary Status
Differences between
ANDAs and NDAs
Orphan drugs
Regulatory requirements
Formularies in health care management and public sector organizations
Outcomes based research
8. Compliance requirements for products
Role of the FDA
Audits, notices and warning letters
Legal implications
Requirements in other countries
9. Generic Drugs
Differentiating generic
drugs
Waxman-Hatch Amendments
FDA office of generic drugs
The Orange book
Rules for ANDAs for generic drugs
When companies market the same drug two ways…
10. Post-marketing Surveillance Studies and Adverse Event Reporting
Defining adverse
events
Structuring and organizing post-market surveillance
When and where to report adverse events- Medwatch
When to call a lawyer
11. Transitioning from Prescription to OTC Status
Durham Humphrey Amendments
OTC Drug review
Switch regulations
Labeling and advertising
Cosmetics that are also drugs
Tamper-resistant and poison-prevention packaging
12. Compliance requirements for drugs and biologics (GMP, GLP, GCP)
Quality issues
Review of relevant regulations
13. Packaging, Labeling and Advertising Issues: Recent trends
Package inserts
MeGuide
Kefauver-Harris Amendments
Role of FTC
Educational roles
14. Regulation and Trends in Biological Product Development; CMC evaluation
for the comparability of biologics; vaccines
CBER
Preapproval requirements
Well-characterized biologics
Biologics license applications
Blood facilities regulations and video
15. Regulation of Drugs and Biological Products in Other Jurisdictions
Constituencies and
jurisdictions
EU rules and harmonization
Canada and its role as portal to Europe
China
Clinical trials and drug marketing in the third world
Course Requirements and Grades:
Midterm test: 20%
Final examination: 50%
Research paper: 30%
At the end of the course students should be able to demonstrate a competent knowledge of the subject matter by formal examination. Students will also write a research paper on a topic selected in consultation with the course instructors. The research paper will be evaluated on the basis of the following criteria:
- Clear introduction
to the issue or problem under study
- Review of current guidelines and identification of regulatory requirements
- Identification of other issues including policy issues
- Relevant research related to policy formulation
- Current bibliography in annotated format
Text books:
Mathieu, Mark (1997)
Biologics Development: A Regulatory Overview. 2nd ed Parexel: Waltham,
MA
Mathieu, Mark (1997) New Drug Development: A Regulatory Overview, 4th
ed. Parexel: Waltham, MA
Reference material will also be provided in the form of a reading list,
and some of these references will be distributed in class
Attendance and Conduct:
The Student Handbook, SCampus and University Catalogue provide guidance regarding academic policies and procedures. Students should regard the program as a part of their professional development in which courtesy and responsibility are significant factors in success. Thus, students are expected to communicate absences from class and are expected to attend all examinations and class presentations. Under normal circumstances, papers and exams must be submitted on or before the scheduled deadlines. Failure to make appropriate arrangements in case of justifiable delay will result in a penalty of 10% in the assigned mark for the first two weeks of delay, and further penalties for additional unapproved delays.
N.B. Reference texts and links are not updated regularly.
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TOPIC READING
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1.The drug development
path; Drug classes Food and Drug Administration Act of 1992 Public Law
105-115, 105th Congress
Mathieu M (1994) New Drug Development: A Regulatory Overview Ch 3, 4rd
ed. Parexel: Waltham, MA
The Drug Price Competition and Patent Term Restoration Act PL 98-417 98 Statute 1585
Clissold DB (1995) Prescription for the Orphan Drug Act: The impact of FDA's 1992 Regulations and the latest Congressional proposals for reform. Food and Drug Law Journal 50:125-147
Linberg, SE. (1995) Expediting Drugs and Biologics Development. Parexel: Waltham, MA
2.Investigational New Drugs: chemical and animal testing to support human trials Content and format of investigational new drug applications for phase I studies of drugs including well-characterized, therapeutic, biotechnology-derived products, CBER, CDER, (on web)
3.Bioavailability and Pharmacokinetics Bioavailability and Bioequivalence,
Chap 10, in Applied Biopharmaceutics and Pharmacokinetics, Leon Shargel,
Andrew B.C. Yu. 4th ed. pp 247-279. Appleton & Lange:Stamford, Conn,
1999.
USP 24 NF 19 2000. <1088> In vitro and In vivo Evaluation of Dosage
Forms, pp 2051-2056.
USP 24 NF 19. <1090> In vivo Bioequivalence Guidelines, pp 2056-2098.
4.Investigational
New Drugs contd: Planning and implementation of clinical trials Guidelines
for the monitoring of clinical trials, CDER (on web)
Bernstein, D.F. and Hamrell, M.R. Managing Clinical Trials Materials to
Speed Clinical Trials. Appl. Clin. Trials. 8(9):77-84, 1999
5.New Drug Applications:
chemistry, manufacturing and controls requirements Taylor, MR (1984) Food
and Drug Administration regulation of color additives- Overview of statutory
framework. Food, Drug Cosmetic Law Journal 39: 273-280
Rumore, MM et al., Regulatory aspects of color additives. Pharmaceutical
Technology. 16: 68-82
Chow, S and Liu, J (1994) Recent statistical developments in bioequivalence trials- A review of the FDA guidance. Drug Information Journal 28: 851-864
Demmer, F et al. (1994) Regulation of bulk pharmaceutical chemicals Part I Pharmaceutical Technology October: 80-88
6.New Drug Applications:
Compilation and analysis of animal and human data Guidelines for Drug
Master Files, CDER (on web)
Hamrell, M.R. Good Laboratory Practices and Compliance. The Validation
Consultant. 5(6):4-7, 1998
7.Abbreviated New
Drug Applications; Obtaining Formulary Status Abbreviated New Drug Application
Regulations Final Rule 57 Federal Register 17 April 28, 1992
Abbreviated New Drug Application Regulations Final Rule 59 Federal Register
October 3, 1994
8.Compliance Requirements for products Hamrell, MR (2000), The Clinical Audit in Pharmaceutical Development. Marcel Dekker, NY., Spilker, B (1991) Guide to Clinical Trials. Raven Press, NY
9.Generic Drugs Molzon, JA (1995) The generic drug approval process. Journal
of Pharmacy and Law 5:275-284
Beers DO (1995) Generic and innovator drugs: A guide to FDA approval requirements.
4th ed. New York: Aspen Law and Business Ch 8,9
Hamrell, M.R. An Update on the Generic Drug Approval Process. Clin Res Reg Affairs. 14:139-154, 1997.
10. Post-marketing Surveillance Studies and Adverse Event Reporting Expected safety reporting requirements for human drug and biological products. Final Rule, 59 Federal Register 207, October 7,1994
11. Transitioning from Prescription to OTC Status Covington TR (1996)
Handbook of Non-Prescription Drugs. 11th Ed. American Pharmaceutical Association
Washington DC pp 1-15
Voluntary Codes and Guidelines for the OTC Medicines Industry. Non-prescription
Drug Manufacturers Association, Washington, DC
Baumgartner, KC (1988) A historical examination of the FDA’s Review of the Safety and Effectiveness of over-the-Counter Drugs. Food, Drug and Cosmetic Law Journal 43:463-94
Nonprescription Drugs. Over the Counter and Underemphasized. GAO Report to the Chairman, Subcommittee on Regulation, Business Opportunities and Energy, Committee on Small Business, house of Representatives, January 1992, GAO/PEMD-92-9
Pinco. RG A legal perspective on regulatory approaches to switch. Drug Information Journal 24:5-11
Oppenheimer, DC (1997) It’s Been a Long Four Years- FDA’s OTC Drug Product Review. Pharmaceutical Technology 21:64-66
12. Packaging, Labeling
and Advertising Issues: Recent trends Jones, PA (1997) A fine line between
advertising and promotion. Regulatory Affairs Focus 2:6-9
Final Guidance on Industry-Sponsored Scientific and Educational Activities
Federal Register October 3, 1997
Abbod RR and Brushwood DB ( 1994) Pharmacy Practice and the Law Gaithersburg: Aspen Publishing pp 182-193
Brown SA Unscrambling the meaning of the Prescription Drug Marketing Act. Pharmaceutical Executive November 68-73
13. Regulation and
Trends in Biological Product Development Zoon, KC (1994) Initiatives and
new structure at the Center for Biologics Evaluation and Research. Regulatory
Affairs 6: 201-219
Frantatoni, J (1997) FDA's modified approach to biologics: Fundamental
changes Reg Affairs Focus 2:18-19
Mathieu M (1997) Biologics Development: A Regulatory Overview 2nd ed. Parexel: Waltham, MA Ch 4-6
Adverse Experience reporting requirements for licensed biological products. Final Rule 59 Federal Register, 207, October 27. 1994 (on web)
CFR part 600
Guideline for Quality Assurance in Blood Establishments July 11. 1995 (on web)
14. Sterilization and packaging TBA-speaker
15. Regulation of Drugs and Biological Products in other Jurisdictions
Schroff, AP (1995) FDA Import/Export Enforcement Regulatory Affairs 175-184
The Drug Export Act PL 104-134 April 6, 1996
Simmons, R. ed. (1993) Multi-Company, Multi-Country Clinical Trials. Buffalo Grove, IL: Interpharm Press
