MPTX 513: Regulation of Medical Devices
Instructors: Frances
J Richmond, PhD School of Pharmacy, USC
Enid Rokaw, MSc, President, EBR Consulting Group
Guest lecturer,Gerald E Loeb, MD, Dept of Biomedical Engineering, USC
Course weight: 3 units
Placement: Latest agenda (may be from previous class)
UPCOMING COURSE SCHEDULE
Introduction and Purposes:
The medical device industry is one of the most vibrant and important drivers of the economy of Southern California. Regulations to ensure the safety of devices and in vitro diagnostics are evolving rapidly in both the US and the international arena. In this course, students with a basic knowledge of biomedical science and regulatory structures will explore in depth the policies and practices of regulatory research and management for these product classes. At the completion of the course, students should exhibit a detailed understanding of American and international laws, policies and regulations. They should be able to integrate this knowledge with scientific principles related to the development of experimental protocols and testing paradigms, in order to plan and manage complex research programs.
Some of the knowledge and skills developed by the student should include the ability to:
Classify any medical
device or diagnostic into its appropriate product class, and understand
the regulatory significance of this classification
Understand the requirements for 510K and PMA submissions to market new
devices
Understand the engineering requirements for assuring product safety and
quality
Understand the aims and range of testing needed to evaluate biocompatibility
Design an animal testing plan for an assigned implantable device
Develop a strategy for developing a combination drug/device product
Identify time points to meet with regulatory agencies and agenda items
to be discussed at those meetings
Organize a third-party audit of a device manufacturing facility
Understand the current rules regarding single-use vs reuse devices
Describe the differences between product approval in the US and Europe/Asia
Be able to identify the steps to obtain a CE mark
Describe the requirements for post-marketing surveillance and adverse
event reporting
Some parts of the course will be taught through case studies presented
by the students. 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 half and full days in the summer term totaling 40
face-to-face hours.
This syllabus may not reflect recent changes or additions.
Course Requirements and Grades:
Midterm test: 20%
Final examination: 50%
Case study: 30%
At the end of the course students should be able to demonstrate a competent
knowledge of the subject matter as appraised by formal examination. In
addition, students will be assigned to teams. Each team will be assigned
a case study in which an appropriate research or testing plan must be
developed for a medical device or in vitro diagnostic. The research plan
will be submitted as a paper and a brief class presentation.
The
research paper will be evaluated on the basis of the following criteria:
- Clear introduction
of the problem to be solved
- Review of current guidelines and identification of regulatory requirements
- Identification of other issues that affect testing plan
- Specification of testing or research protocol
- Identification of potential problems or biases that cannot be eliminated
- Timeline and budget for the research or testing plan
Course Outline:
Course topics are identified in three-hour blocks. In addition to these classroom blocks students will participate in two one-hour computer labs in which electronic databases will be used for information retrieval and submission.
1. Introduction to US Regulations for new medical devices and diagnostics
Relevant laws
Historical development of regulations
Organization of FDA and CDRH
Washington
Field offices
Role of FTC and other regulatory bodies
Computer Lab I-FDA and Federal Register databases
2. Engineering management:
Design control and
qualification review
Risk assessment
Faults and hazards analysis using HACCP, fault-tree and quantitative methods
3. Biomaterials; basic concepts and testing
Failure mechanisms
of metals and polymers
Electrical and electronic components and functions
Bench testing for mechanical integrity
Accelerated life testing
Cytotoxicity testing
4. In vitro and in vivo biocompatibility testing of finished devices
Importance of device
class and risk category
Cytotoxicity
Irritation and sensitization
Genotoxicity and carcinogenicity
Implantation
Hemocompatibility
5. Clinical trial development
Matching trials to
immediate and future claims
Submission of an IDE (Investigational Device Exemption) application
6. The 510 K clause and 510K applications
Key points to consider
before beginning the process
Interacting with the ODE
Elements of a 510(k)
Abbreviated and special 510(k)s
510(k) case studies
7. Obtaining premarket approval through the PMA or PDP route
Parts of the dossier
Planning and managing the process
Negotiating and budgeting approaches
Modular PMAs
Computer Lab II: Application procedures and electronic submissions
8. Quality Systems Regulations
Comparison with earlier
Good Manufacturing Practices and with ISO and other standards
Design history files
QSIT auditing methods
9. Post-market tracking and adverse event reporting medical device
MedWatch
Responsibilities of user facilities, distributors and manufacturers
Device tracking and patient registration
(visiting speaker TBA)
10. European philosophy and rules
Trends in the harmonization
of requirements
Medical Device, Active Medical Device and IVD directives
CE marking: choosing a notified body
export certificates
11. Blood products and products of human and animal tissue origin
Autologous cells
Allogenic cells
Non-viable tissue for soft-tissue repair
Current policies and developing trends in US and international arena
12. Sterilization and packaging
Principles and comparative
applications of :
EtO
Radiation
Plasma
e-beam
X-ray
UV light
Chemical methods
Single use and reuse devices
(visiting speaker TBA)
13. Labeling and advertising
What information
is needed
Symbols, language considerations
Proof of single use
Internet advertising
Product monographs and brochures
Recommended Textbook:
N.B. subject to change.
Kahan, Jonathan S, (2000) Medical Device Development: A Regulatory Overview 2000. Parexel Int Corp: Chicago
The textbook will be supplemented by a list of readings that will compliment the text. In some cases in which the reading is necessary to cover topics outside of the scope of the text, materials will be available in hand-outs. Additional relevant materials will also be provided as a reader at a modest charge.
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 by their colleagues. Under normal circumstances, papers and exams must be completed on the day that they are scheduled for submission. Failure to make appropriate arrangements in case of justifiable delay will result in a penalty of 10% in the assigned mark.
N.B. Reference texts and links are not updated regularly.
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TOPIC READING
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1. Introduction to
US Regulations Food and Drug Administration Act of 1992 Public Law 105-115,
105th Congress
ODE Director memo (1995) Use of international standard ISO 10993, Biological
evaluation of medical devices Part I: Evaluation and Testing
Nobel, JJ (1994) The universe of medical devices. In: Medical Devices: International Perspectives on Health and Safety. ed. CWD van Gruting, Elsevier:Amsterdam, pp 7-19
Appropriate CDRH regulations on FDA web-pages
2. Product Design
and Engineering Fries RC (1997) Risk management. In: Reliable Design of
Medical Devices, Marcel Dekker: New York pp 245-272
Johnson M, DeWitt M and Hammond S (1999) HACCP in the medical device industry.
Regulatory Affairs Focus May:10-15
Wheble VH (1994) Design validation through clinical testing. In: Medical Devices: International Perspectives on Health and Safety. ed. CWD van Gruting. Elsevier:Amsterdam, pp 53-74
3. Biomaterials testing
Black J (1994) Material response: function and degradation of materials
in vivo. In: Biological Performance of Materials: Fundamentals of Biocompatibility.
2nd ed, Marcel Dekker: New York pp 25-109
ASTM F 148 (1982) Standard Practice for Selecting Generic Biological Test
Methods for Materials and Devices ASTM, Philadelphia PA USA
4. Biocompatibility
testing of devices ISO 10993-1 (1996a) Biological Evaluation of Medical
Devices Part I: Evaluation and Testing. ISO, Geneva, Switzerland
ASTM F 813-83 (1983) Standard practice for direct contact cell culture
evaluation of materials for medical devices. ASTM, Philadelphia PA USA
ASTM F895-84 (1984) Standard test method for agar diffusion cell-culture screening for cytotoxicity ASTM Philadelphia PA
ISO (1994) Biological evaluation of medical devices. Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity. ISO Geneva, Switzerland
Ames BN, McCann J and Yamasaki E (1975) Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test.
Vince DG, Hunt JA and Williams DF (1991) Quantitative assessment of the tissue response to implanted biomaterials. Biomaterials 12:731-737
5. Clinical trial
development CFR 21, part 812 Investigational Device Exemptions. Health
and Human Services
Gad SH (1997) Clinical studies for medical devices. In: Safety Evaluation
of Medical Devices Marcel Dekker Inc, New York pp 317-338
6. The 510 K clause and applications CDRH (1995) Premarket Notification 510(k): Regulatory requirements for medical devices. HHS Publication FDA 95-4158, US Department of Health and Human Resources, Public Health Service
7. Obtaining premarket approval by PMA or PDP Guidelines on FDA web-site;
8. Quality Systems Regulations CFR Part 820 Quality System Regulation,
Federal Register FDA Oct 7, 1997
ISO (1994) Quality Systems: Model for quality assurance in design, development
production, installation and servicing. ISO 9001
9. Post-market tracking
and adverse event reporting Spilker, B (1996) Interpretation of Adverse
reactions In: Guide to Clinical Trials, Lippincott-Raven: Philadelphia,
pp565-599
Medical Devices; Device tracking; New Orders to Manufacturers. Federal
Register 63: 42 pp10638-10640, March 4, 1998
10. European philosophy
and rules CEN EN 14630 (1996) Non-active surgical implants- general requirements.
CEN, Brussels, Belgium
CEN EN 1441 (1997) Medical devices- risk analysis. CEN, Brussels, Belgium
EC (1990) Council directive 90/385/ EEC concerning active implantable medical devices L 189 (20 July) :17-24 OJEC Brussels
EC (1993) Council directive 93/42/EEC concerning medical devices L169 (12 July): 1-43. OJEC. Brussels. Belgium
Shapiro, JK (1999) Next steps for the mutual recognition agreement. RAPS Focus 1:26-34
11. Blood; Products
of human and animal origin Anderson JM (1993) Cardiovascular device retrieval
and evaluation Cardiovascular Pathology 2:199S-205S
Anderson J (1997) Interactions with blood In: Biocompatibility Assessment
of Medical Devices and Materials. Wiley: Chichester pp129-151
Dieners P (1999) Medical devices incorporating medicinal substances of human origin in the European Union: Current status and expected changes. Regulatory Affairs Focus May pp33-35
63 Federal Register 60, 122 (Nov 6, 1998) (final regulations adding 21 CFR Part 26
Medical devices incorporating medicinal substances of human origin in the European Union: Current status and expected changes, RAPS Focus 4,5: 33-35
12. Sterilization
and packaging Dorma-Smith, V Sterilization processes and residuals In:
Biocompatibility Assessment of Medical Devices and Materials. Wiley, Chichester,
pp 101-107
Ref: Morrissey RF and Briggs G (eds) Sterilization technology: a practical
guide for manufacturers and users of health care products. Phillips-van
Nostrand Reinhold, Amsterdam
Speaker materials to be distributed
13. Labeling and
advertising CDRH Device Labeling Guidance 3/8/91 General Program Memorandum
91-1 (www.fda.gov/cdrh/G91-1.html)
Pilot, L (1999) Medical device Labeling in the European Union MDDI May:1999
