1. The Quality System Regulations
RMRAS - June, 2016

2. Introductions

3. Brian Schwarz Senior Manager Quality Management Systems, Terumo BCT
Brian oversees the Audit (Internal, External, and Supplier), CAPA, and Management Responsibility processes. 
Prior to joining Terumo BCT, he spent 10+ years as Quality Engineering Manager for Becton Dickinson, where he managed a team focused on validation, incoming and in-process QA, new product / process development, and Continuous Improvement. 
Brian is a Six Sigma Master Black Belt, and has extensive experience in Quality Engineering and compliance readiness and remediation. 

4. Matthew Bickford Quality Manager, Terumo BCT
Matthew is a Colorado native with a diverse background in the Pharma, Biotech, and Medical Device industries. 
After graduating with a degree in Molecular, Cellular, and Developmental Biology and Biochemistry, his career began in pharmaceutical manufacturing and product development. 
He then moved into biotech as a validation professional before his current role as Quality Manager at Terumo BCT, where he works within the Quality Management System group and specifically oversees the global recall and adverse event processes. 
Matthew has 15+ years of experience in FDA regulated product industries and has a graduate degree in Engineering Management with an emphasis in new product ventures and process development. 

5. Rod Lenoble Senior Quality Manager, Terumo BCT
Rod has over 25 years of experience in the medical device and pharmaceutical industries, focusing on Quality Management Systems (development, implementation, and management), laboratory management (chemistry, microbiology, and calibration), and FDA and ISO compliance. 
Over his career, he has gained substantial experience in developing and improving quality system processes for compliance with FDA and ISO. Rod has developed, implemented, and managed CAPA systems, Non-conformance systems, Training systems, Global QMS systems, and has set up and managed numerous chemistry, microbiology, and calibration laboratories. 
Rod received his Masters of Business Administration from the University of Phoenix and his Bachelor of Science in Chemistry from State University of New York College at Oneonta. 
Prior to joining Terumo BCT, Rod was the Technology Director for Hauser Inc, an Active Pharmaceutical Ingredients manufacture.  

6. Participant Introductions
Name
Company
Position
Specific section of the regulation that you are especially interested in or have specific questions.

7. Introduction to the Quality System Regulation Course

8. Course Contents 21 CFR 820 Quality System Regulation Overview course
Basic understanding and knowledge of each section of the regulation.
Interpretation of the regulations
Practical recommendations for compliance.
Consequences of non-compliance.

9. Not included in Course Content
There are many FDA and international regulatory requirements beyond 21 CFR 820 that medical device companies must comply with:
21 CFR 4 cGMP Requirements for Combination Products
21 CFR Electronic Records; Electronic Signatures
21 CFR 801 Labeling
21 CFR 803 Medical Device Reporting
21 CFR 806 Corrections and Removals
21 CFR Establishment Registration, Device Listings, (k) Premarket Clearance
21 CFR In Vitro Diagnostics
21 CFR Medical device recall authority
21 CFR Investigational device exemptions
21 CFR Premarket approval of medical devices
21 CFR Medical device tracking requirements
21 CFR Postmarket surveillance
ISO Medical devices - Quality management systems
ISO Medical devices - Application of risk management to medical devices
ISO General requirements for the competence of testing and calibration laboratories
Reference may be made in our presentations, but in depth discussion is beyond the scope of this course.

10. Quality System Regulation vs. ISO 13485
Although the Quality System Regulation is “harmonized” with ISO13485, the interpretation and compliance expectations of the FDA are dramatically different from your notified body.
FDA
Performs inspections for the purpose of determining compliance to federal regulations.
FDA inspectors carry badges.
FDA has many legal actions they can take to enforce compliance.
Do not assume that having ISO certification and successful ISO audits means that you will meet FDA’s compliance expectations.

11. Conventions Used in Presentation

12. Conventions Used in the Presentation
Regulations
Interpretation and recommendations for compliance

13. Conduct of the Course Interactive Course Materials Provided
Participation is expected and encouraged
Course Materials Provided
Slides
21 CFR 820 Quality System Regulation

14. Quality System Regulation -Background and History

15. Food and Drug Administration (FDA)
Department of Health and Human Services (HHS)
Food and Drug Administration (FDA)
Center for Devices and Radiological Health (CDRH)
Office of Compliance
Field Inspections
Recalls
Enforcement

16. FDA Responsibilities
Protecting the public health by assuring the safety, efficacy and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation.
Advancing the public health.
Regulating the manufacturing, marketing and distribution of tobacco products.
Counterterrorism:
Ensuring the security of the food supply.
Fostering development of medical products to respond to deliberate and naturally emerging public health threats.

17. FDA Enforcement Actions - Authority to Protect Public Health
Inspection
Voluntary Corrections
FD-483 Notice of Observations
Untitled Letters
Warning Letters
Mandatory Corrections
Mandatory Recall
Injunctions/ Seizures
Consent Decrees
Legal Action
Civil Money Penalties
Criminal Indictments

18. FDA Inspections and QSIT
QSIT – Quality System Inspection Technique
Inspectional process that is used to assess a medical device manufacturer’s compliance with the Quality System Regulation and related regulations.
4 Major Subsystems
Management Controls (MGT)
Design Controls (DES)
Corrective and Preventive Actions (CAPA)
Production and Process Controls (P&PC)

19. FDA Inspections and QSIT
Within each subsystem, provides:
Inspection Objectives
Decision flowchart
Narrative
The QSIT Manual is available on the FDA website:

20. CTQ Inspection Technique
Suplements the QSIT Technique
Focus on key attributes of a product (CTQ’s)
How are user needs identified, incorporated into design, and managed through product life cycle?

21. Regulatory Hierarchy Federal Laws Federal Regulations (CFR)
Guidance Documents

22. Federal Law Enacted by Congress
Federal Food Drug and Cosmetic Act (FFD&C)
Civil and Criminal act
Violations of the Act can be tried in Civil or Criminal court
Both Companies and Individuals can be held liable for violations of the Act.

23. Code of Federal Regulations (CFR)
Implementation of Federal Laws
Written by the governing agency
Published in the Federal Register
Proposed Rule
Notice and Comment Period
Final Rule
Preamble to the Final Rule
21 CFR 820 Quality System Regulation
tRequirements/QualitySystemsRegulations/ucm htm
Intent of Congress and FDA
Purpose of the Regulation
Response to Comments- provides insight into FDA interpretation
Legally binding in a court of law

24. Guidance Documents Do not have the legal force of Law or Regulation
“Contains Nonbinding Recommendations”
“FDA's guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.”
Informative
Express the Agency’s position
Interpretation of the regulations
Roadmap for compliance

25. Quality System Regulation - History
The quality systems regulations for medical devices were originally known as current good manufacturing practices (cGMP’s).
cGMP requirements for medical devices were first authorized by the 1976 Medical Device Amendments to the Federal Food, Drug, and Cosmetic Act.
21 CFR 820, prescribing cGMP requirements for medical devices, became effective in 1978.
Only governed the manufacturing of medical devices.
No authority over the design of medical devices.

26. Quality System Regulation - History
Safe Medical Devices Act of 1990
Authorized revisions to cGMP
Design Controls
44 percent of the quality problems that led to voluntary recall actions during were attributed to errors or deficiencies in device design.
Over 90 percent of all software related device failures were due to design-related errors, generally, the failure to validate software prior to routine production.
Management Review
Harmonization with ISO 13485
Quality System Regulations (21 CFR 820)
Published 1996 , Effective 1997

27. Flexibility of the Quality System Regulation
The regulation is a framework that specifies the requirements that each manufacturer must incorporate into their quality management system.
The regulation does not prescribe how to implement the requirements.
Within the regulation framework, each manufacturer must develop a quality management system that is appropriate to their devices and business:
Risk class of the device
Type of device
Sterile> Process Controls (e.g. controlled environments, sterilization validation)
Software> Design Control (e.g. software development and validation)
Complexity of the device
Complexity of the manufacturing process
Size of the organization

28. CDRH Inspections

33. Warning Letters Are Public Info

34. Quality System Regulation - Content

35. Quality System Regulation -Content
Acceptance Activities
Management Responsibility
Non-Conforming Product
Quality Audit
Corrective and Preventive Action
Personnel
Labeling and Package Control
Design Controls
Handling, Storage, Distribution and Installation
Document Controls
Records
Purchasing Controls
Servicing
Identification and Traceability
Statistical Techniques
Production and Process

36. Quality System Regulation

37. Quality System Regulation
Definitions of “System”:
“A set of connected things or parts forming a complex whole.”
“A group of related parts that work together as part of an interconnecting network”
The individual requirements of the regulation do not standalone.
They are interdependent, providing inputs and outputs to other requirements or subsystems.
As we discuss each section of the regulation, we will point out how that section links with other requirements of the regulation.