Industrial Regulation and Quality CHMG 751

1. Industrial Regulation and Quality CHMG 751 Manhattan College Fall 2012 Class 3

2. Agenda • Review Homework Assignment No. 3 QFD Exercise • Review Homework Assignment No. 4 Dairy Case Study • GxPs • Break • Introduction Quality Systems • Quality Control/Regulatory Affairs Role • Organizational Structures supporting Quality • Quality Culture, Governance and Mgt Techniques • Homework No. 5 • Term Paper/Presentation • Next Week Topics

3. Homework Assignment No. 3 QFD Exercise • Products • Customer Needs • Product Features/Requirements • Process Design Elements • Process Parameters/Key Performance Indicators

4. Homework Assignment No. 4 Dairy Case Study • What were the main takeaways? • Did you agree or disagree? Why? • How would you improve the author(s) points? • Are there alternative rationales? • How can you broaden or expand the case study?

5. GxPs • Concept of Good Practices • The purpose of the GxP quality guidelines is to ensure a product is safe and meets its intended use. GxP guides quality manufacture in regulated industries including food, drugs, medical devices and cosmetics. • The most central aspects of GxP are: • Traceability: the ability to reconstruct the development history of a drug or medical device. • Accountability: the ability to resolve who has contributed what to the development and when. • Documentation is a critical tool for ensuring GxP adherence.

6. GxPs • Many types of GxPs • We will focus on just a few • GLC • GCP • GMP • GDP

7. GxPs • Good Laboratory Practices (GLP) • In the experimental (non-clinical) research arena, the phrase good laboratory practice or GLP specifically refers to a quality system of management controls for research laboratories and organizations to try to ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of chemical (including pharmaceuticals) non-clinical safety tests; from physio-chemical properties through acute to chronic toxicity tests.

8. GxPs • Good Laboratory Practices (GLP) • GLP embodies a set of principles that provides a framework within which laboratory studies are planned, performed, monitored, recorded, reported and archived. These studies are undertaken to generate data by which the hazards and risks to users, consumers and third parties, including the environment, can be assessed for pharmaceuticals (only preclinical studies), agrochemicals, cosmetics, food additives, feed additives and contaminants, novel foods, biocides, detergents etc.... GLP helps assure regulatory authorities that the data submitted are a true reflection of the results obtained during the study and can therefore be relied upon when making risk/safety assessments. GLP, a data quality system, should not be confused with standards for laboratory safety - appropriate gloves, glasses & clothing to handle lab materials safely.

9. GxPs • Good Clinical Practices(GCP) • is an international quality standard that is provided by International Conferences on Harmonization (ICH), an international body that defines standards, which governments can transpose into regulations for clinical trials involving human subjects. • Good Clinical Practice guidelines include protection of human rights as a subject in clinical trial. It also provides assurance of the safety and efficacy of the newly developed compounds. • Good Clinical Practice Guidelines include standards on how clinical trials should be conducted, define the roles and responsibilities of clinical trial sponsors, clinical research investigators, and monitors. In the pharmaceutical industry monitors are often called Clinical Research Associates.

10. GxPs • Good Manufacturing Practices (GMP) • is a production and testing practice that helps to ensure a quality product. Many countries have legislated that pharmaceutical and medical device companies must follow GMP procedures, and have created their own GMP guidelines that correspond with their legislation. Basic concepts of all of these guidelines remain more or less similar to the ultimate goals of safeguarding the health of the patient as well as producing good quality medicine, medical devices or active pharmaceutical products. In the U.S. a drug may be deemed adulterated if it passes all of the specifications tests but is found to be manufactured in a condition which violates current good manufacturing guidelines. Therefore, complying with GMP is a mandatory aspect in pharmaceutical manufacturing.

11. GxPs • Good Manufacturing Practices (GMP) • Although there are a number of them, all guidelines follow a few basic principles: • Manufacturing processes are clearly defined and controlled. All critical processes are validated to ensure consistency and compliance with specifications. • Manufacturing processes are controlled, and any changes to the process are evaluated. Changes that have an impact on the quality of the drug are validated as necessary. • Instructions and procedures are written in clear and unambiguous language. (Good Documentation Practices) • Operators are trained to carry out and document procedures.

12. GxPs • Good Manufacturing Practices (GMP) • Records are made, manually or by instruments, during manufacture that demonstrate that all the steps required by the defined procedures and instructions were in fact taken and that the quantity and quality of the drug was as expected. Deviations are investigated and documented. • Records of manufacture (including distribution) that enable the complete history of a batch to be traced are retained in a comprehensible and accessible form. • The distribution of the drugs minimizes any risk to their quality. • A system is available for recalling any batch of drug from sale or supply. • Complaints about marketed drugs are examined, the causes of quality defects are investigated, and appropriate measures are taken with respect to the defective drugs and to prevent recurrence.

13. GxPs • Good Manufacturing Practices (GMP) • 21 CFR 211: cGMP in Manufacturing, Processing, Packing or Holding of Drugs and Finished Pharmaceuticals • Subpart A General Provisions • Subpart B Organization and Personnel • Subpart C Buildings and Facilities • Subpart D Equipment • Subpart E Control of Components and Drug Product Containers and Closures • Subpart F Production and Process Controls • Subpart G Packaging and Labeling Control • Subpart H Holding and Distribution • Subpart I Laboratory Controls • Subpart J Records and Reports • Subpart K Returned and Salvaged Drug Products

14. GxPs • Good Manufacturing Practices • GMP guidelines are not prescriptive instructions on how to manufacture products. They are a series of general principles that must be observed during manufacturing. When a company is setting up its quality program and manufacturing process, there may be many ways it can fulfill GMP requirements. It is the company's responsibility to determine the most effective and efficient quality process.

15. GxPs • Good Distribution Practice (GDP) • Deals with the guidelines for the proper distribution of medicinal products for human use. GDP is a quality warranty system, which includes requirements for purchase, receiving, storage and export of drugs intended for human consumption. • GDP regulates the division and movement of pharmaceutical products from the premises of the manufacturer of medicinal products, or another central point, to the end user thereof, or to an intermediate point by means of various transport methods, via various storage and/or health establishments.

16. Introduction to Quality Systems • What is a Quality System • Holistic approach to develop a system to address quality within an organization • Quality System needs to have a • Quality Vision: Define a long-term ultimate goal • Organizational Mission Alignment • i.e. “Make High Quality products for our customers” • Quality Strategy: How are we going to get there • Quality Plan: Tactical elements to support day to day activities

17. Introduction to Quality Systems • All industries should have quality systems to support their strategy and operational needs • Quality Systems can be expressed • Implicitly • Built into Culture • Explicitly • Quality System is expressly defined • Standard Operating Procedures

18. Introduction to Quality Systems • Pharmaceuticals • Clear regulatory position • Explicit defined and managed • FDA Inspections are based upon five systems • Production System • Facilities and Equipment Systems • Material Systems • Packaging and labeling systems • Laboratory control systems

19. Introduction to Quality Systems • ICH Q10 Pharmaceutical Quality System • Based upon ISO quality concepts • Scope covers the development and manufacture of drug substance and drug products including biotechnology and biological products • Product Lifecycle • Pharmaceutical Development • Technology Transfer • Commercial Manufacturing • Product Discontinuation • Objectives • Achieve Product Realization • Establish and maintain a state of control • Facilitate Continual Improvement

20. Introduction to Quality Systems • ICH Q10 Pharmaceutical Quality System • Enablers of a Quality System • Knowledge Management • Quality Risk Management • Quality Manual • Quality Policy • Scope • Identification of Quality System Processes • Management Responsibilities • Commitment • Establish of Quality Policy and Quality Objectives • Resource Management • Communication • Oversight of Outsource Activities and Purchased materials • Change Management

21. Introduction to Quality Systems • ICH Q10 Pharmaceutical Quality System • Continual Improvement of Process Performance and Product Quality • Process performance and product quality monitoring system • Corrective action and preventative action (CAPA) • Change management System • Management review of process performance and product quality Will cover more in next week’s lecture….

22. Quality Control/Regulatory Affairs Role • Quality Assurance and Quality Control Groups • Some industries do not separate • Pharmaceuticals, Medical Device and Food: Do separate roles • Quality Control: Measures the quality aspects of the product with in process or laboratory analysis • Quality Assurance: focuses on ensuring the quality systems are in place, addresses deviations, investigations, audits, improvement plans

23. Quality Control/Regulatory Affairs Role • Regulatory Affairs Group: • Interface with government bodies: Federal, State, Municipal (Local) • Bridge between science and legal affairs • Provide interpretation and consulting of regulations to the organization • Registration Documentation to agencies • Food and Drug Administration (i.e. IND, NDA, post approval changes) • OSHA (i.e. complaints, hazard communications, MSDS) • EPA (i.e. environmental impact statements, permits, licenses) • Interface with Quality Assurance and Quality Control in matters of manufacturing compliance

24. Organizational Structures supporting Quality • Roles of Senior Management • Provide strategic direction • Ensure resources are available • Middle Management • Support operators • Operators • Move quality inspection to the front line from separate function • Quality control laboratory testing moving to factory floor • New Forms • Self Managing Teams such as Quality Circles • Cross Functional Groups such as a Quality Council

25. Organizational Structures supporting Quality • Quality Organization • Coordinates for control (maintain level) • Coordinates change to ensure final end point will meet quality objectives • Quality Assurance and Control part of the larger organization

26. Organizational Structures supporting Quality • Regulatory Affairs Department • Standalone • Sometimes part of Legal

27. Quality Culture, Governance and Management Techniques What does it mean to have a Quality Culture?

28. Quality Culture, Governance and Management Techniques • What does it mean to have a Quality Culture • Express a set of behavior, beliefs and values that continually views quality as a primary goal • Focus on the customers needs • Drives activities to support those needs • Individuals feel accountability and responsibility • Aware of and execute activities to support regulatory needs

29. Quality Culture, Governance and Management Techniques • Governance • Quality councils, steering committees • Develop clear quality goals • Strong leadership prioritize quality importance • Self directing or self managing teams • Empowers teams to take responsibility and accountability • Examples: project teams, factory floor, quality circles

30. Quality Culture, Governance and Management Techniques • Management Techniques • Theories Motivation • Maslow Hierarchy • 5 levels of motivation • Starting at the physiological level must be met before moving to the next level of safety • And so….

31. Quality Culture, Governance and Management Techniques • Management Techniques • Theories Motivation • Hertzberg: Job Dissatisfaction and Satisfaction • They are not opposites • Management must consider both categories • Satisfaction • Satisfaction comes from what the employee does • Motivation form job challenges, opportunity for creativity, • Dissatisfaction • Comes from specific dislikes such as pay is low, working conditions are poor

32. Quality Culture, Governance and Management Techniques • Management Techniques • Theories Motivation • McGregor: Theory X and Theory Y

33. Quality Culture, Governance and Management Techniques • Management Techniques • Job Design: how to structure the work and the individual responsibility. • Embed responsibilities beyond the task level • Group tasks as much as possible to get the unit product such as a chemical batch, packaging lot, etc. • Ability to recognize errors/defects in the product • Ability to recognize changes in the process, • Support with performance metrics to build self correcting behavior such as key performance indicators, statistical process control • i.e. Quality is someone else’s responsibility

34. Quality Culture, Governance and Management Techniques • Management Techniques • Delegation: • Appropriate level and representation to deal with quality issues • Too little with involvement by management can also be a problem (lose touch with the plant activities

35. Quality Culture, Governance and Management Techniques • Management Techniques • Participatory Management Style • Involvement by all necessary parties • Manufacturing, R&D, engineering, quality control/assurance

36. Quality Culture, Governance and Management Techniques • Management Techniques • Philosophy of continuous improvement • Ability to make small incremental changes • Larger quantum level improvements with projects

37. Quality Culture, Governance and Management Techniques • Management Techniques • Change Management • Kotter Model

38. Quality Culture, Governance and Management Techniques • Management Techniques • Change Management • Leadership vs. Management

39. Quality Culture, Governance and Management Techniques • Management Techniques • Rewards and Recognition • Performance objectives defined on a personal level with compensation awards to those specific quality objectives • Quality Awards: company wide recognition

40. Quality Culture, Governance and Management Techniques What happens when we depend upon suppliers or outsourced manufacturing activities?

41. Quality Culture, Governance and Management Techniques • Supply Chain Perspective • Quality who owns it? • Is there accountability? • How do we create shared responsibility? • Selecting the right supplier • Quality Agreements • Ongoing collaboration

42. Homework No. 5 • Case Study: After Heparin: Protecting Consumers from the Risks of Substandard and Counterfeit Drugs • Review it from the perspective of • GMPs and GDPs • Quality Systems • Culture, Governance, Organization and Management Techniques • Follow critical analysis guidance in syllabus • Will be using for next week’s assignment also

43. Paper/Presentation Topics • Need to start thinking about a topic • Topics can be anything related to Industry Regulation or Quality • Due September 26th

44. Next Week • Module 4 Quality Systems Continued • Training • Documentation Systems • Change Control • Quality Audit • Quality Risk Management • Inspection and Compliance