This document provides an overview of a quality systems approach. It discusses key elements like design controls, production and process controls, corrective and preventive actions, management reviews, and continuous improvement. The quality system aims to design quality in from the beginning, execute according to design, and monitor and control through quality assurance. It also discusses applying this approach to pharmaceutical development and manufacturing through concepts like an integrated validation master plan and quality evaluations.

1. Quality Systems Approach Overview
Corrective &
Preventive
Actions Production &
Design Controls
Process Controls
Management
Material Equipment &
Controls Facility Controls
Records,
Documents, &
Change Controls

2. Quality System
Alignment and Integration
Continuous Improvement
Design Execute Monitor/Control
Design – determine what is really important
Execute – translate into service and manufacturing
Monitor/Control – translate into quality assurance

3. Example: Pharmaceutical

4. Capability and Control Cycle
Development History
Integrated Validation Master Plan
process product systems
Begin with the End in Mind
2. Compliant Establish shared standards
3. Capable Process Flow Document and expectations
4. Robust
5. In Control
6. Continuously Improving Technology Transfer
Qualification
Document with FDA in Mind
2. Clear Execute and monitor with
3. Concise Validation process and product best business practices.
4. Correct
5. Complete Execute, Monitor and Control
6. Confident
Technical Evaluations process and product Quality (GMP) Evaluations quality systems
Change Control process and product Change Control quality systems
Assess results against the
standards and practices.
Quality Management System

5. Balanced Scorecard

6. Behavior Needed
Dominance
Influence
Conscientiousness
Steadiness
Selection

7. Situation
People
Action
Result
Consequence

8. Scenario
Worst Case
Most Likely Case
Best Case
Decision

9. Plan
Approach
Deployment
Result

10. Responsibility of Highest Level
of Management
Establish Quality Policy
Ensure that it is followed

11. Delegation by Management
with Executive Responsibility
Establishment of quality objectives
Translation of objectives into
methods and procedures
Implementation of quality system

12. How does Management Assure
an Effective Quality System?
CAPA
Management
Audits
Review

13. How to Demonstrate Compliance
Procedures ...
Verbal Communications
Written records and documents

14. Establish [21 CFR 820.3(k)]
Define
Document
Implement

15. Key Elements of a Quality Manual
1. Generation and maintenance of master production
batch records.
2. Generation of routine batch records
3. Generation and maintenance of Standard Operating
Procedures
4. Generation and maintenance of preventive maintenance
procedures
5. Generation and maintenance of calibration procedures
6. Generation and maintenance of equipment logbooks
7. Generation and maintenance of cleaning procedures
8. Generation and maintenance of deviation/failure reports
9. Generation of rework procedures

16. Key Elements of a Quality Manual
1. Training programs and records for all employees
2. In-coming inspection program for raw materials
3. In-process analytical checks during processing
4. Inventory control
6. Validation of equipment/systems/processes
7. Cleaning validation
8. Analytical methods validation
9. Computer/controller validation
10. Validation change control
11. Revalidation program

17. Key Elements of a Quality Manual
1. Audit programs - internally and externally
2. Qualification of vendors
3. Quality Control testing (in-process and finished product
testing)
4. Complaint handling program
5. Annual product reviews
6. Stability Program
7. Sample retention program
8. Documentation control/storage
9. Labeling and label control
10. Specification development
11. Generation and validation of analytical methods

18. Writing and Managing
Standard Operating Procedures
Controls
Approvals
Formatting
Readability
Change History
Cross References

19. Developing Batch Records CFR 211.188
Prepared for each batch of drug
product produced
Include complete information
relating to production and control of
each batch (signed, dated and checked accurate reproduction of
master production or control record, documentation of accomplished significant
steps in manufacture, processing, packing or holding – dates, equipment and lines,
specific identification of components and in-process material, ….)

20. Document Management
Structure
Segregation
 Documents in Review
 Documents in Approval
 Effective Documents
 Archived Documents
Control

21. Complaint Management CFR 211.198
Mechanism
 Designated person in quality group
 Logged with unique number
 Sender
 Detail
 Sample
 Appropriate storage conditions
 Investigation methodology
 Response
 Reference book

22. Annual Product Review CFR 211.180 (e)
FDA Requirement
Annual Reports
 Summary of all findings
 Sent to FDA by product NDA anniversary date
Review of batches
 Deviations
 Failures
 Out of Specifications
 Stability Profiles
 Visual verification
 Retained samples

23. Managing Regulatory Training
Compliance CFR 211.25
Education, Training, and Experience
Enable to perform assigned functions
 Particular operations performed
 Current Good Manufacturing Practice
 Written procedures related to assigned functions
Continuing basis
Sufficient frequency
Documented
Follow-up

24. How does Management Assure
an Effective Quality System?
CAPA
Management
Audits
Review

25. (Your Organization’s Name)
Regulatory Responsibilities
Job Title/Employee Quality System 21 CFR Part 211 Subparts
A B C D E F G H I J K

26. Management
Production &
Design Controls
Process Controls
Corrective &
Preventive
Actions
Material Equipment &
Controls Facility Controls
Records,
Documents, &
Change Controls
Controls

27. (Your Organization’s Name)
Regulatory Responsibilities
• What are the responsibilities?
• Where are the gaps?
• What are the risks?
• What are the consequences?
• What are the opportunities?
• What are the rewards?

28. QUESTIONS