MPTX 519: International Approaches to Medical-Product Regulation

Instructors:

Eun-Joo Pacifici, Pharm D, PhD Adjunct Professor, School of Pharmacy USC
Richard Meissel, MA, JD, CEO, Propel Biomedical Consulting
Jaap Laufer, MD, PharmD, EMDAR DV

Course weight: 3Units
Placement: fall term, 2003, Five full days, times TBA

Introduction and Purposes:

The marketplace for medical products is global. Increasingly, companies recognize the importance of global sales to ensure the financial success of the company. In addition development, clinical testing and manufacturing of products is increasingly conducted overseas. This advanced course in Regulatory Science is designed to compare the laws, regulations and institutions governing medical products in North America with those of several other countries and groups of countries, including the major trading blocks of the European Community and Asia. Particular attention will be paid to regulations that shape the developmental path and marketing applications for drugs, biologics, and medical devices in the EU but other constituencies will be considered in comparison. The students should understand the history that has led to the different regulatory approaches used by other countries. Students will also become familiar with the regulations shaping the structure and conduct of preclinical and clinical trials in other countries, including developing countries in which ethical considerations are often very important to understand.

The course will be taught through case studies and lectures. An emphasis will be placed on relatively informal lecture formats in which students are encouraged to ask and answer questions throughout the didactic sessions. As part of a novel strategy to meet the needs of part-time as well as full-time students, the course will be taught in a condensed period of full days; lecture-discussions will occupy a total of approximately 40 face-to-face hours. The course will be team-taught to ensure that students have exposure to experts who have worked in different international constituencies.

Course Objectives:

Below are listed some of the capabilities and knowledge expected of students who graduate from this course. Students should be able to:

Explain the evolution of the integrated EU system for drug and device regulations, and be able to relate these developments to economic imperatives in Europe
Chart the process by which drugs are approved by the centralized procedure through the European Medicines Evaluation Agency
Explain the rationale for selecting either the Centralized procedure, Mutual Recognition procedure or National procedure for the approval of a specific type of drug
Explain the considerations that go into selecting a lead country when the Mutual Recognition procedure is used
Draw a flow chart to explain the drug development and approval process in Japan
Be able to identify if a drug or device would qualify for orphan product status in different countries
Describe the differences in the application process for the approval to market a generic vs an innovative drug product in Europe, Canada and Japan
Describe the role and recent accomplishments of the International Council for Harmonization
Be able to report an adverse reaction worldwide and how they interface with the US system.
Classify devices according to risk according to the Canadian and European systems and identify the approach that would need to be used to commercialize each type of product
Explain how compliance is assessed in at least three constituencies globally
Identify three current issues of concern when clinical trials are conducted in underdeveloped countries, and how these concerns can be addressed successfully

Course Outline:
Course content is divided into three-hour blocks. 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.

Class sessions:

1. World-wide overview
Commercialization pressures Harmonization efforts
Reimbursement considerations
Distribution channel requirements

2. History of regulation in Europe; current organization of EU regulatory bodies overseeing drug development and marketing
Development of pharmaceutical legislation
Overview of National Health Authorities
Review of the mutual recognition procedure and national procedure
Review of the Centralized Procedure
Case studies to identify when different procedures are used
OTC vs prescription drugs

3. European Approaches to New Device Marketing
The “new” approach to product approvals
Classification of medical devices
Path to securing a CE mark
Choosing a notified body
Labelling and special rules that govern entry into specific countries
Risk assessment

Computer lab

4. The Canadian Regulatory System
Steps to drug commercialization
Device classification and regulatory submissions
Import-Export rules and concerns
Postmarket reporting requirements

5. The Japanese Regulatory System
The organizational structure of relevant bodies for drug approvals
Device approval systems compared to the US and EU
Import-export concerns

6. Clinical trials for drugs and devices in the EU
Good clinical Practices
Identifying subjects, informed consent
Ethics Boards
The role of the Competent Authority in different countries

7. Clinical Trials for drugs and devices in other constituencies
The Japanese system under change
Rules for clinical trials in selected constituencies
Dealing with the coercive elements of trials in developing countries
Auditing and distributing clinical supplies to other constituencies
What does the US FDA need to know?
Clinical Trials directives
Bridging studies

8. Quality Systems and Conformity Assessment
Directives, guidances and standards
Legal requirements and implementation of GMPs
Differences between drug and device oversight in Europe
Assessment of quality in Asian constituencies

9. Regulation of foods, dietary supplements and cosmetics
Defining boundaries between products in different constituencies
Regulations concerning genetically engineered products
Rules governing labelling and claims
Mad Cow disease and other problems of cross-border contamination of foods
Dietary supplements vs over-the counter drugs: rules in different constituencies

10. Regulation of Biologicals and Human Tissue Products
Products derived from human blood or plasma
Biologically Engineered drugs
In Vitro Devices with or without biologically based constituents

11. Post-marketing Assessments and Concerns
Country by country comparison of reporting requirements
Adverse events reporting-when where and how?
Managing recalls internationally
Counterfeit drugs and smuggling
Pricing products in different constituencies
The internet and cross-border product procurement

Course Requirements and Grades:

Midterm test 30%
Final examination 35%
Research paper 30%
Class participation 5%

At the end of the course students should be able to demonstrate a competent knowledge of the subject matter by formal examination. Students will work in pairs to make a class presentation on a case-study topic selected in consultation with the course instructors. This presentation will be accompanied by a written paper of no more than 6 double spaced pages. The presentation will be evaluated by the class and instructors using the appended evaluation sheet (Fig 1). The research paper will be evaluated on the basis of the following criteria:

Clear introduction to the issues or problem raised by the case study
Review of current guidelines and identification of regulatory requirements, if applicable
Identification of other issues including policy issues
Appropriateness of suggested approaches to problems identified from the case study
Well-structured presentation and written report
The presentation is worth a total of 30% 0f the final grade. Of this total, 10% is based on the presentation and 20% on the written paper.

An important element of performance in business and government is the ability to ask questions and participate in discussions. The level of engagement and participation of each student will be assessed by the instructors and speakers.