Harmonizing Change Control Processes Globally

Transcription

1 Quality & Compliance Associates, LLC Harmonizing Change Control Processes Globally

2 President Quality & Compliance Associates, LLC

3 When We Deal In A Global Environment, How Do We Design A System That Addresses International Needs?

4 Regulatory, Quality, and Business Requirements for Change Control 4

5 Regulatory Requirements Traditional FDA Requirements 5

6 FDA Reference Documents CFR 211 cgmp s Compliance Program Guidance Manual for FDA Staff: Drug Manufacturing Inspections Program CFR APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG CFR 820 Medical Devices CFR 110 Dietary Supplements 6

7 Compliance Program Guidance Manual for FDA Staff: Drug Manufacturing Inspections Program Quality Laboratory Packaging & Labeling CONTROL SYSTEM FOR IMPLEMENTING CHANGE Facilities & Equipment Materials Production 7

8 Expectations Change control system must address changes that impact the identify, strength, quality, potency and purity of your drug product. Under the quality system, there must be a documented change control system that requires all changes to be evaluated, approved, and need for re-validation assessed. Quality has final approval for all changes. 8

9 Additional FDA Guidance SUPAC BACPAC Changes to a NDA 9

10 EMEA EudraLex - Volume 4 Good manufacturing practice (GMP) Guidelines. 10

11 Rules Governing Medicinal Products in the European Union Volume 4 Principle Quality Assurance Good manufacturing Practice for Medicinal Products Quality Control Product Quality Review Quality Risk Management 11

12 EudraLex The Rules Governing Medicial Products in the European Union 12

13 Quality Assurance Development Self Audit Production Shipping Controls Managerial Responsibilities QA Final QP Cerification Material Traceability Finished Product Controls In-Process Controls 13

14 GMP Complaints Process Definition Critical Control Points Recall System Shipping Controls GMP Facilities Instructions And SOP s Batch Records In-Process Records Training 14

15 Quality Control Retention Sample Program Appropriate QC Facilities Approved QC Sampling Plans QP Certification QC Validated Test Methods Inspection Records Finished Product Testing Data Recording 15

16 Product Quality Review Facilites Equipment Contractual Arrangements Starting Materials In-Process And Finished Product Results Appropriate Investigation Failed Batches Post Marketing Commitments Review Investigations Review Corrective Actions Complaints Recalls Returns Stability Review Marketing Authorizations Changes 16

17 Quality Risk Management Systematic process for performing risk assessment Evalution of the risk to quality is based on scientific knowledge, experience with the process and ultimately links to the protection of the patient. The level of effort, formality and documentation of the quality risk management process is commensrate with the level of risk. 17

18 ICH 10 Important Guide 18

19 ICH Q10 Innovation, continual improvement, the outputs of process performance and product quality monitoring and CAPA drive change. In order to evaluate, approve and implement these changes properly, a company should have an effective change management system. The change control process is critical to ensure that change is controlled and approved for all phases within the pharmaceutical environment. ICH 10 links key elements to the stage of the process life cycle. 19

20 Q10 Key Elements Quality risk management should be utilized to evaluate proposed changes. Proposed changes should be evaluated relative to the marketing authorization. Proposed changes should be evaluated by expert teams contributing the appropriate expertise and knowledge. After implementation, an evaluation of the change should be undertaken to confirm the change objectives were achieved and there were no adverse impact on product quality. 20

21 Q10 Application of Change Management System in Lifecycle Development Technology Transfer Product Discontinuation Commercial Manufacturing 21

22 PIC/S Pharmaceutical Inspection Convention 22

23 PIC/S' mission is "to lead the international development, implementation and maintenance of harmonised Good Manufacturing Practice (GMP) standards and quality systems of inspectorates in the field of medicinal products." 23

24 How Will This Be Achieved This is to be achieved by developing and promoting harmonised GMP standards and guidance documents; training competent authorities, in particular inspectors; assessing (and reassessing) inspectorates; and facilitating the co-operation and networking for competent authorities and international organisations. FROM PIC/S WEBSITE 24

25 As from 1 January 2011

26 Members Argentina Australia Austria Belgium Canada Cyprus Czech Republic Denmark Estonia Finland France Germany Greece Hungary Iceland Ireland Israel Italy Latvia Liechtenstein Lithuania Malaysia Malta Netherlands Norway Poland Portugal Romania Singapore Slovak Republic South Africa Spain Sweden Switzerland Ukraine United Kingdom USA (Jan 1, 2011) 26

27 FDA Becomes A Member in January,

28 Pharmaceutical Inspection Convention CHANGE CONTROL 43. Written procedures should be in place to describe the actions to be taken if a change is proposed to a starting material, product component, process equipment, process environment (or site), method of production or testing or any other change that may affect product quality or reproducibility of the process. Change control procedures should ensure that sufficient supporting data are generated to demonstrate that the revised process will result in a product of the desired quality, consistent with the approved specifications. 44. All changes that may affect product quality or reproducibility of the process should be formally requested, documented and accepted. The likely impact of the change of facilities, systems and equipment on the product should be evaluated, including risk analysis. The need for, and the extent of, requalification and re-validation should be determined. 28

29 Sources of Changes Investigations Annual Product Reviews Building and De-commissioning Development Purchasing Continuous Improvement 29

30 Benefits of An Effective Global Change Control System Structured and consistent approach towards managing change across sites and territories. Accurately document the details of change Routing of change requests to appropriate individuals/team for approvals Documentation of change approvals and implementation Maintenance of change history and easy retrieval of information Tracking changes effectively Demonstration of change effectiveness Demonstrate compliance to regulations 30

31 Determine Scope for Your Change Control System 31

32 Determine Extent of Globalization First establish a corporate policy. Each critical site should have a procedure that is linked to the corporate policy. Audits/Checks to ensure policy is current and actively reflect corporate and site policies. 32

33 How Are International Activities Linked Are multiple sites making the same product? Are sites acting as contract manufacturers for other sites. Are materials such as excipients, API s, packaging supplies, etc. common sourced? Are there common subcontractors? 33

34 Major Organizations US (North/South America) ROW EMEA Asia Pacific 34

35 Some Simple Questions Who are the key players for change control at each of your major international sites for change control? What are the roles of the site or is there as central control? If a question arises, who do you contact about international site impact? How is conflict resolution handled? 35

36 Define/Map Your Current Processes What procedures currently exist? Review the list of open change controls? Multiple change controls to correct the same event, such as documents. Age of change controls Audit the effectiveness of closed change controls. 36

37 Phases Initiate Implementation Assessment Verification Approval Execute 37

38 Determine GAP s In Your Current Systems Training on the change control SOP and process who should receives it in the organization. Are the SOP s and forms too complicated? Is the thought of doing the change equivalent to root canal. Who is the CC Go To person in the organization. 38

39 Systems for Remediation and Improvement What is the system to correct deficiencies across sites. Is there an audit program that includes review of change control. Key Process Indicators. 39

40 Developing a Harmonized Change Control Process 40

41 Impact of Global Assessments Regulatory Requirements across countries. FDA Regulatory requirements may require filing which can cause wait times in implementation, such as prior approvals. There are international requirements that can also cause wait. However, what if change can be implemented in some countries without filing requirements? 41

42 Coordination Across Global Organizations There has to be a gatekeeper role within the organization All changes have to go through this gatekeeper. One of the first assessments should be impact assessments. What is affected. Are multiple site impacted Scope and objectives. 42

43 Organizational Structures To Ensure Success Initiator. Gatekeeper roles. Change control board or equivalent. Special role of regulatory. Is there a process for reality check. Who controls the change control process. 43

44 Implementation and Verification of the Global Process 44

45 How to Determine Measures of Success Compliance with leadtimes Communication between sites. Training effectiveness. Regular planned meetings with international site representatives. System for resolving roadblocks and conflicts. Audits. 45

46 Key Performance Indicators to Measure Progress Leadtime compliance Metrics for critical points in the process. Implementation of key elements of the change control. Coordination across sites. Open vs. Closed. 46

47 Important components of a Verification System Effectiveness of implementation. Analysis of all change controls on a monthly and annual basis. Types of changes. Repetitive changes. Examples. 47

48 Thank You! 48