change control

change control

1. Change control CH.SRINIVASA REDDY M.SC

2. USFDA Guidance for Industry Change control Change control is another well-known CGMP concept that focuses on managing change to prevent unintended consequences. The CGMP regulations provide for change control primarily through the assigned responsibilities of the quality control unit Certain major manufacturing changes (e.g., changes that alter specifications , a critical product attribute or bioavailability) require regulatory filings and prior regulatory approval (21 CFR 314.70, 514.8, and 601.12).

3. USFDA Guidance for Industry Change control Effective change control activities (e.g., quality planning and control of revisions to specifications , process parameters , procedures ) are key components of any quality system . In this guidance, change is discussed in terms of creating a regulatory environment that encourages change towards continual improvement .

4. USFDA Guidance for Industry Change control

5. ICH HARMONISED TRIPARTITE GUIDELINE Q7 13. CHANGE CONTROL 13.10 A formal change control system should be established to evaluate all changes that may affect the production and control of the intermediate or API . 13.11 Written procedures should provide for the identification, documentation, appropriate review , and approval of changes in raw materials, specifications, analytical methods, facilities, support systems, equipment (including computer hardware), processing steps, labelling and packaging materials, and computer software.

6. ICH HARMONISED TRIPARTITE GUIDELINE Q7 13. CHANGE CONTROL 13.14 When implementing approved changes, measures should be taken to ensure that all documents affected by the changes are revised. 13.15 After the change has been implemented, there should be an evaluation of the first batches produced or tested under the change.

7. ICH HARMONISED TRIPARTITE GUIDELINE Q7 13. CHANGE CONTROL 13.12 Any proposals for GMP relevant changes should be drafted, reviewed , and approved by the appropriate organisational units , and reviewed and approved by the quality unit(s). 13.13 The potential impact of the proposed change on the quality of the intermediate or API should be evaluated. A classification procedure may help in determining the level of testing, validation, and documentation needed to justify changes to a validated process. Changes can be classified (e.g . as minor or major ) depending on the nature and extent of the changes, and the effects these changes may impart on the process . Scientific judgement should determine what additional testing and validation studies are appropriate to justify a change in a validated process .

8. ICH HARMONISED TRIPARTITE GUIDELINE Q7 13 . CHANGE CONTROL 13.16 The potential for critical changes to affect established retest or expiry dates should be evaluated . If necessary, samples of the intermediate or API produced by the modified process can be placed on an accelerated stability program and/or can be added to the stability monitoring program.

9. ICH HARMONISED TRIPARTITE GUIDELINE Q7 13. CHANGE CONTROL 13.17 Current dosage form manufacturers should be notified of changes from established production and process control procedures that can impact the quality of the API.

10. Technical Change Control Guideline - APIC Change Control A system to propose, review, justify, evaluate, document, implement, approve, and close changes to technical equipment used in the manufacture of APIs and intermediates to ensure a constant qualified status of the systems concerned.

11. Technical Change Control Guideline - APIC Emergency change An unplanned change of a piece of equipment as a result of an emergency, which needs to be repaired immediately in order to maintain personal or environmental safety or preserve the quality of the product.

12. Technical Change Control Guideline - APIC " Like for like" Change Replacement of a piece of equipment by another with identical characteristics and function (same material of construction, size, type, etc., but not necessarily from the same manufacturer). The fact if equipment is like for like needs to be thoroughly reviewed, justified and recorded with written approval of the Process Owner, QU and if applicable Regulatory Affairs. These changes can be considered minor impact changes

13. Technical Change Control Guideline - APIC Major impact changes A change expected to have a potential impact on product quality. Changes with an uncertain impact level should be handled as major impact changes. Minor impact changes A change not expected to have an impact on product quality. Also called Standard change.

14. Technical Change Control Guideline - APIC Process owner The person who has the ultimate accountability for the system which is subject of the proposed change. Quality Unit (QU) An organisational unit independent of production that fulfils both Quality Assurance and Quality Control responsibilities. Technical Change A technical change is a planned modification (expansion, replacement, removal, addition) with respect to qualified equipment (defined state of a piece of technical equipment).

15. Technical Change Control Guideline - APIC Technical Equipment : Manufacturing equipment, utilities, computerized systems [e.g. Process (PLC) and Distribution and Control Systems (DCS)] and facilities used in the manufacturing of APIs. Impact of Changes on affected Systems Important repairs and maintenance work, such as replacement of major parts of equipment, may affect the performance of the process and the quality of the product.

16. Technical Change Control Guideline - APIC Impact of Changes on affected Systems Rearrangements in manufacturing areas (for example rooms with defined environmental conditions) and/or support systems (utilities, e.g.: HVAC systems, systems for water, steam, CIP/SIP-systems) may result in changes in the process and therefore, revalidation/requalification may be necessary.

17. Technical Change Control Guideline - APIC Regulatory Affairs Every technical change with major impact should be assessed at least by RA. RA is required to assess the potential impact on regulatory filing. RA decides about the measures to be taken to document the change appropriately. In case an approved change has impact on regulatory filing it is the responsibility of the RA department to take appropriate action.

18. Technical Change Control Guideline - APIC Technical Department : The TD is required to evaluate and approve the (technical) impact of a proposed change. Criteria for criticality can directly contact the product or product components, and is not considered a like for like change

19. Technical Change Control Guideline - APIC can directly affect the product quality by normal operation or control (e.g., impurity profile , crystal form and size, residual solvent or stability of the API); indicates and records alarm functions critical to the process is used to record, output or archive data for batch records or l abels and other GMP documentation or labels;

20. Technical Change Control Guideline - APIC is used to demonstrate compliance with the registered process; can influence the quality and performance of support systems (e.g., water, steam, HVAC , etc.) is used to ensure access control to critical data or functions (user identification and authenticity)

21. Technical Change Control Guideline - APIC is used to perform analytical investigations that are relevant for batch release is used for critical calculations (e.g., analytical data that are relevant for batch release); is used for batch release is used to control batch status or shelf life; is used to control the production process (recipe/process description);

22. Technical Change Control Guideline - APIC is used to transfer critical data (interface) to another quality relevant system; is used to give information about the quality of the product (e.g. printers for process related data); is used to ensure or record critical conditions for warehouses is used to control maintenance or calibration of critical equipment is used to create, modify, record, document, review, approve GMP data;

23. PHARMACEUTICAL INSPECTION CONVENTION / CO-OPERATION SCHEME Concept Note on a Document prepared by the PIC/S QRM Expert Circle on ‘How to Evaluate / Demonstrate the Effectiveness of a Pharmaceutical Quality System in relation to Risk-based Change Management ’ Guidance for GMP Inspectors on evaluating the effectiveness of the PQS in relation to riskbased change management was considered important, given the requirements of the PIC/S GMP Guide in these areas (see below). This specific topic had not been dealt with extensively in the existing training materials of the QRM Expert Circle up until then, but it has become a topic of high relevance at this time, given the pending agreement of ICH Q12 , for which PQS effectiveness in relation to risk-based change management is a core concept

24. PHARMACEUTICAL INSPECTION CONVENTION / CO-OPERATION SCHEME The PIC/S GMP Guide requires companies to demonstrate the effectiveness of their PQS , and it requires the application of QRM principles to change control activities . Principle: …there must be ‘a comprehensively designed and correctly implemented PQS incorporating GMP and QRM . It should be fully documented and its effectiveness monitored’

25. PHARMACEUTICAL INSPECTION CONVENTION/ CO-OPERATION SCHEME 1.3 ...’the e ffectiveness of the system is normally demonstrated at the site level ’ 1.5 ‘ Senior management has the ultimate responsibility to ensure an effective PQS is in place...’ 1.4 (xii) Arrangements [should be] in place ‘for the prospective evaluation of planned changes and their approval prior to implementation

26. PHARMACEUTICAL INSPECTION CONVENTION /CO-OPERATION SCHEME Annex 15 states: 11.1. ‘The control of change is an important part of knowledge management and should be handled within the pharmaceutical quality system.’ 11.4. ‘Quality risk management should be used to evaluate planned changes… and to plan for any necessary process validation, verification or requalification efforts.’

27. PHARMACEUTICAL INSPECTION CONVENTION /CO-OPERATION SCHEME Details of the Document on How to Evaluate / Demonstrate PQS Effectiveness for Riskbased Change Managemen The key elements that could be included in risk-based change proposals. The assessment by the pharmaceutical manufacturer of change proposals from a risk perspective , where the level of rigor, effort and documentation is commensurate with the level of risk, where risk assessments adequately assess potential risks and benefits of changes to product quality, safety and efficacy, and where those risk assessments assess the potential risks and benefits to other products, processes, systems.

28. PHARMACEUTICAL INSPECTION CONVENTION I/ CO-OPERATION SCHEME The categorisation by the pharmaceutical manufacturer of changes based on the level of risk. The role of change planning and implementation, where the outcomes of risk assessments and the assigned risk levels drive change planning, prioritisation , implementation, and their timelines

29. PHARMACEUTICAL INSPECTION CONVENTION /CO-OPERATION SCHEME Change review and effectiveness assessments at the pharmaceutical manufacturer, in terms of whether changes meet their intended objectives and pre-defined effectiveness criteria, where residual risks are assessed and managed to acceptable levels, and where changes are monitored via ongoing monitoring systems to ensure maintenance of a state of control.

30. PHARMACEUTICAL INSPECTION CONVENTION / CO-OPERATION SCHEME Anticipated Benefits of the Document The document will deliver benefits in several ways. For the QRM Expert Circle, for example, it can serve as the basis for the development of practical training materials and case studies for GMP inspectors in relation to inspecting the effectiveness of the PQS with regard to risk-based change management activities

31. PHARMACEUTICAL INSPECTION CONVENTION /CO-OPERATION SCHEME Anticipated Benefits of the Document In addition, the principles set out in the document could be used to assist in updating the current PIC/S QRM Aide Memoire, to delineate a risk-based approach for inspecting change management programmes In addition, the PIC/S GMP Guide requires companies to use risk-based approaches to the management of changes. Therefore, PQS effectiveness and risk-based change management go hand-in-hand and indeed, they complement each other..

32. PHARMACEUTICAL INSPECTION CONVENTION / CO-OPERATION SCHEME There are additional benefits from having guidance in this area also. ICH Q10 sets out the potential for risk-based regulatory oversight for companies which demonstrate that an effective PQS is in place. ICH Q10 indicates that, if the principles and concepts of ICH Q8, Q9 & Q10 are adopted

33. PHARMACEUTICAL INSPECTION CONVENTION I/ CO-OPERATION SCHEME if the effectiveness of the PQS is demonstrated, then there may be opportunities for some form of risk-based regulatory oversight from regulators to promote lifecycle continual improvements. This concept was also a cornerstone principle behind FDA’s 21st Century GMP initiative, published in 2002.

34. SOP Any proposal to good manufacturing process)relevant changes related to SOP,Forms,Facility,equipment instrument,process,specification&MOA and method of analysis. and other shall be proposed ,reviewed and evaluated by the appropriate departments.and reviwed approved by the QA department.

35. SOP Change shall be planned to always occur and there fore action shall be prospectively defined and approved prior to carrying out change. A deviation is not a plan and there fore refers to un international changes or occurrence are from an approved instruction or established stranded. the reference to the term deviation Shall be same as incident under company quality system.

36. SOP Change control process shall be a formal system by which qualified representative of appropriate discipline review and approve change request. the review and approval shall Include assessment . The ownership of the change shall be with the Head of the department, who is responsible for initiating the change in “Change Control Initiation Form” .

37. SOP Identification of ownership of the change and consent to be taken from the other departments is mentioned in “Change Control Initiation Matrix. Initiation of Change Control Change Control Initiator shall describe the following in “Change Control Initiation Form”.

38. SOP Name of the Initiator department and Name of the product and Stage of production Code of change in section The change(s) proposed Identification of change(s) either temporary (with period) or permanent in section Reason(s) for proposing the change Tentative date of implementation of change with batch number

39. SOP Initiator department shall attach supporting documents (if applicable) based on proposed change. The following types of documents are to be attached with “Change Control Initiation Form” , but not limited to : R&D / Process Development Laboratory data in case of manufacturing process change. Recommendation from other agencies / departments. Past Trend Analysis Data. Audit Observation

40. sop Change in Regulatory norms / guidelines. The type of reason may be as follows, but not limited to Regulatory requirement. Good manufacturing practices implementation / enhancement. Quality improvement. Capacity enhancement. Introduction of new product in the existing Facility. Cost reduction.

41. SOP Automation. Aging of Facility. To manage unavoidable situation. Market requirement. Safety requirement

42. sop CHANGE CONTROLE INTIATION FORM Date; 1.1 Change initiation change control No: CCIF   1.2 INITIATION DEAPARTMENT   1.3 CHANGE RELATED TO □ BATCH RECORDS □ PROCESS □ FACILITY □ SPECIFICATION □ DOCUMENT □ Equipment □ Test procedure □ others       1.4 Existing documents / document title :   Existing system current version _______ to   Ref deviation if applicable __________

43. SOP IMPLEMENTATION APPROVED CHANGE : After completion evaluation and approval of process QA Representative shall communicate The same to request to implement approve of the change. requester shall refer the details of instructions/remarks/actions/documents identified evaluators and approves CCF during evaluation and approval.

44. SOP Evaluation of change : Request shall forward the change control to identify the internal department personal for evaluation. During evaluation any information required the evaluator shall contact requester .each evaluator shall give their decision.

45. SOP Closing of change control . After completion of post change review by request department, QA Representative shall Review the results and supporting data. Verify the completion of required activities / documents identified during the evaluation and approval of change and record details of verification in change control.

46. Volume 4 EU Guidelines The control of change is an important part of knowledge management and should be handled within the pharmaceutical quality system. Written procedures should be in place to describe the actions to be taken if a planned change is proposed to a starting material, product component, process, equipment, premises, product range, method of production or testing, batch size, design space or any other change during the lifecycle that may affect product quality or reproducibility.

47. Volume 4 EU Guidelines Where design space is used, the impact on changes to the design space should be considered against the registered design space within the marketing authorisation and the need for any regulatory actions assessed.

48. Volume 4 EU Guidelines Quality risk management should be used to evaluate planned changes to determine the potential impact on product quality, pharmaceutical quality systems, documentation, validation, regulatory status, calibration, maintenance and on any other system to avoid unintended consequences and to plan for any necessary process validation, verification or requalification efforts.

49. Volume 4 EU Guidelines Changes should be authorised and approved by the responsible persons or relevant functional personnel in accordance with the pharmaceutical quality system. Supporting data, e.g. copies of documents, should be reviewed to confirm that the impact of the change has been demonstrated prior to final approval.

50. Volume 4 EU Guidelines Following implementation, and, where appropriate, an evaluation of the effectiveness of change should be carried out to confirm that the change has been successful. Change Control . A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect the validated status of facilities, systems, equipment or processes. The intent is to determine the need for action to ensure and document that the system is maintained in a validated state.

51. Reference: Reference: Volume 4 EU Guidelines PHARMACEUTICAL INSPECTION CONVENTION /CO-OPERATION SCHEME ICH HARMONISED TRIPARTITE GUIDELINE Q7 Technical Change Control Guideline – APIC Guidance for Industry Quality Systems Approach to Pharmaceutical CGMP Regulations