MPTX 515: Quality Systems and Standards
Instructors: Al Hans,
Hans and Associates
John Malloy, Malloy and Associates, Inc
Frances Richmond, School of Pharmacy, USC
Course weight: 3 units
Placement: Latest agenda (may be from previous class)
UPCOMING COURSE SCHEDULE
Introduction and Purposes:
During the past forty years product quality assurance has evolved from the simple tasks of material and product inspection to the current implementation of total quality management and reliability engineering. An essential tenet of regulatory oversight is the assurance of quality through guidelines, audits and inspections. In this course, the regulations and guidelines to ensure quality will be studied to understand the basic principles important for interpretation and implementation.
By the end of the program, students should be able to:
- Understand the
difference between quality assurance and quality control
- Describe the requirements of ICH and ISO standards
- Recognize the elements added to the FDA’s Quality Systems - Regulations
that are not present in Good Manufacturing Practices for - - - Drugs or
in good Manufacturing Practices for Foods
- Be able to design sampling protocols according to accepted statistical
methods
- Identify the essential elements in a document control system
- Know the rules for the development of electronic document systems
- Be able to conduct a preliminary systems audit
- Understand the formal tools available to conduct a faults and hazards
analysis
- Recognize the strengths and limitations of currently available methods
for product cleaning and sterilization
- Students will work in teams to develop appropriate testing plans and
documentation for assigned projects in quality control.
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 session. Students will carry out audits of a facility governed by good manufacturing practices or good laboratory practices. 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 days in the summer term; lecture-discussions will occupy a total of approximately 40 face-to-face hours.
This syllabus may not reflect recent changes or additions.
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. Introduction to quality assurance and quality control
What differentiates
quality assurance from quality control
Where do good manufacturing practices fit?
Where to find the guidelines
Vocabulary
Goals vs implementation
2. Fundamentals of good manufacturing practices
Drugs vs devices
Validation and verification
What needs to be governed
Manufacturing traceability and documentation
Personnel and training
Facilities and equipment
3. Quality Systems Regulations
Quality plans and
high-level strategies
Roles of different individuals
Design history files (intro)
Risk management
Software management
4. ISO standards, ICH guidelines and EC Directives
Roles of Competent
Authorities and Notified bodies
CE marks
Electrically active devices
5. Cleaning; sterilization and microbiological quality control
What methods are
available
When and how to validate
Bioburden and dirt
Outside vs in-house sterilization
Clean rooms and clean room management
6. Design control, Design history files; Human factors analysis
Stages in design
Elements in an acceptable design history file
Integrating bench, animal trials and human trials in files
Methods for human factors analysis
7. Good laboratory practices
Basic tenets of GLP
Visit to a laboratory that conducts work under GLP guidelines
8. Validation and verification activities as part of quality assurance
The role of sampling
in quality control
Working with biostatisticians
Validation reports
Complaints and defective products
Recalls
Software testing methods; What should a non-expert know?
9. Document control systems and standard operating procedures
Configuration management
Writing standard operating procedures
Travellers
Case report forms and other data records
Laboratory notebooks
Computer Laboratory
10. Managing technical drawings; managing electronic records and signatures
Guest lecturer (TBA)
Elements of a technical drawing
Electronic records-security and confidentiality
Validating and maintaining electronic records
11. Audits of industrial sites; working with FDA auditors
Organizing an internal
audit
Working with the division of compliance
Responding to audit reports and warning letters
12. Management practices to assure compliance with quality procedures
Developing timelines
and budgets for implementing quality systems
Obtaining management support and involvement
Project management tools
13. Post-audit presentations and discussion
Course Requirements and Grades:
At the end of the course students should be able to demonstrate a competent knowledge of the subject matter as appraised by an end-of-term examination. However, students will also be to present a short case-study illustrating the application of a particular regulatory requirement, and will work in a group to define a testing and auditing plan for a laboratory or industry site.
Examination: 50%
Case study (class presentation): 20%
Group project (presentation plus paper): 30%
The auditing plan 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
Identified questions and approaches to evaluate quality issues under study
Relevant research related to identified approach
Current bibliography and identification of standards
Textbook:
No one book will cover all aspects of this complex subject, but we recommend strongly the following textbook:
Hough, GW, Rawlings, DA and Turner, MF (1997) Pre-production Quality Assurance for Healthcare Manufacturers. Interpharm Press: Buffalo Grove IL
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. Introduction to
quality assurance and quality control Institute for Quality Assurance:
What is quality? http://www.iqa.org/
Chapter 1, textbook
2. Fundamentals of
good manufacturing practices for drugs and foods Chapter 4, textbook
Textbook pp198-216
3. Quality Systems
Regulations 21 CFR Parts 808, 812, and 820 Medical Devices; Current Good
Manufacturing Practice
(CGMP) Final Rule; Quality System Regulation http://www.fda.gov/cdrh/humfac/frqsr.html
Medical Device Quality Systems Manual:A Small Entity Compliance Guide, First Edition (Supersedes the Medical Device Good Manufacturing Practices [GMP] manual) http://www.fda.gov/cdrh/dsma/gmp_man.html
Textbook pp 240-256
4. ICH guidelines
and EC Directives Guide to Good Pharmaceutical Manufacturing Practice
for Medicinal products. Commission Directive 91/356/EU (Medicinal Products
for Human Use) ECSC-EU-EAEC, Brussels Luxembourg, 1992
Textbook Chapter 6, 9
5. Cleaning; sterilization
and microbiological quality control Clark, RN Determining acceptance criteria
for cleaning process validation. In: Cleaning validation, IVT:Royal Palm
Beach
Davis, RJ (1993) Cleaning validation-Midatlantic Region Inspection Guide.
US FDA
FDA (1993) FDA Guide to Inspections of Validation of Cleaning Processes on FDA website
Chesky SR (1996) Cleaning and disinfection- Selection of biodecontamination parameters/materials and their applications. J Val Tech May 1996
Gad, SC (1997) Sterility, sterilization and heavy metals. IN: Safety Evaluation of Medical devices. Marcel Dekker: New York pp 305-316
USP 1990a) Sterility tests. In: United States Phamacopeial Convention: Rockville MD pp:483-1488
Nair, PD (1995) Currently practiced sterilization methods-some inadvertent consequences. J Biomat. Appl. 10:121-135
6. Design control,
Design history files; Human factors analysis ORA Inspectional References
Guide to Inspections of Quality Systems (August 1999) http://www.fda.gov/ora/inspect_ref/igs/qsit/qsitguide.htm
Sawyer, Dick Do It By Design: An Introduction to Human Factors in Medical
Devices http://www.fda.gov/cdrh/humfac/doit.html
Chapter 2,3, 5 Textbook
7. Sampling procedures
and associated statistical tests good laboratory practices 21 CFR Part
58 Good Laboratory Practice for Nonclinical Laboratory Studies. Provided
in class
Military Standard 105D (1963) Sampling procedures and tables for inspection
by attribute. US Department ofDefense
Textbook pp175-186
8. Validation and verification activities as part of quality assurance Textbook chapter 7
9. Document control systems and standard operating procedures Textbook,
pp123-136
10. Managing technical drawings; managing electronic records and signatures
Speaker TBA
Mazan, KD (1999) Implementation of the Food and Drug Administration’s
electronic records and electronic signatures rule. Reg Affairs Focus,
4, 8, August, pp18-20
11. Software testing
methods Speaker TBA
Textbook pp 211-215
12. Audits of industrial
sites; working with FDA auditors Chapter 7, textbook
RAPS Film
13. Management practices
to assure compliance with regulatory procedures
Flowcharting:http://home.att.net/~dexter.a.hansen/
Textbook chapter 5
