Change control:- Change control is a strategic activity to bring about changes in document/process/method. It can be for the smaller period of time or it can be long term usable. It must be informed to all the concerned departments for official approval of Change Control.
Following procedure is applies for change control: –
- The procedure should always begin with a request for a change. This request should be formalized in some way, for example as a form, and be signed.
- The request triggers the question of the impact of the change on the product quality/safety of the population. It can be necessary to define several levels of impact on product quality but there should be at least two categories; major and minor impact. The treatment of these two options should be clearly different.
- There should be clear rules for the decision, whether the impact of the change on the product quality and/or on study is major or minor: who decides and why the decision is taken.
- For the management of changes, an early decision is required of who should be involved. The decision should be taken by the process owner, who normally has the best knowledge of the impact of changes on the product or study (or at least can estimate it with a high degree of certainty). The principle of double checking should be implemented at this point of the procedure. A signature by the technical department is first required. Depending on the company’s or sponsor’s procedure, the quality unit can be involved as an approver to check periodically by self-inspection audits.
- If the owner has decided that the change is minor and there is no likely to impact on the quality of the product, it can be implemented. The change should be adequately documented.
- The implementation of the changes with minor impact can be achieved in a very rapid and efficient manner using checklists of standard changes. The list of these changes should have been approved by the quality unit.
- If the decision has been taken that the change can or will have an impact on the quality of the product and/or safety of the population, the quality unit has to be involved. An adequate rationale and an appropriate action plan should accompany such request. This builds the basis for the approval by the quality unit.
- After the Quality Unit approval, the change can be implemented. If other aspects are affected by the change, for example safety aspects, additional release activities can be needed. Where such activities have been defining, these should be fulfilled before the refuse of the equipment. Release of the equipment itself can be one of these activities.
- The start of a change control system for technical equipment should be established after the completion of qualification. This will ensure that the qualified status is maintained.
- Change control before completing qualification need not possess the same degree of formality as it can be easier regulated and can proceed without the formal and immediate involvement of the quality unit. The required activities in this case are adequate documentation of the changes and a periodical adaption of the documentation.
- The change requests for emergency changes can be formalized after the replacement. Emergency cases should be defined by each company in an appropriate way.
Documentation: – “All changes should be formally requested, documented and accepted by representatives of production, QC/QA, R&D, Engineering and Regulatory Affairs as appropriate. The likely impact (risk assessment) of the change on the product should be evaluated and the need for, and the extent of Re-validation discussed. The change control system should ensure that all notified or requested changes are satisfactorily investigated, documented and authorized”.
“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, re-qualification and re-validation should be determined.”
Change control requires a written procedure (change control program) to regulate at least the following points: –
- What types of changes does change control take into account; for which areas does this operating instruction apply?
- Who can suggest/initiate changes?
- How changes are requested (forms, methods of communication)?
- How changes are graded, who is responsible for the grading?
- How are the measures necessary for carrying out the change determined; who compiles the directions required?
- Who is responsible for the execution and monitoring of all necessary measures?
- How is the change controls committee assembled; what are the duties of the committee?
- How the change is documented (format, content, storage)?
- Who is responsible for authorizing changes?
- What are the special regulations for urgent changes?
Change requests: – Changes requiring control are generally documented in the form of a change request, in which the applicant for the change proposes the type of grade/evaluation of the change, specifies the time frames and measures for carrying out the change, and requests that and the change is authorized or declined by the change control committee. The documentation for the change procedure should prove that the change was evaluated (risk analysis) and the subsequently defined measures were implemented as predetermined.
Post approval change management protocol: – A post-approval change management protocol describes specific changes that a company would like to implement during the lifecycleof the product and how these would be prepared and verified. It is a step-wise approach in the assessment of changes, which allows an early evaluation of the strategy for the change and a later separate evaluation of the data produced based on the agreed strategy. Such a stepwise approach is expected to lead to faster and more predictable implementation of changes post-approval, since the MAH will have obtained agreement from the Regulatory Authorities about the proposed strategy and tests to verify the effect of the change on product quality.
Content of the change management protocol: – In general, in order to support the proposed change, the company should submit all relevant information that can demonstrate that it has acquired adequate knowledge to prepare and manage the impact of the change.
The content of the protocol could include the following, depending on the nature of the change. Justification that there is a recognized future need for the specific change within a reasonable timeframe and that adequate knowledge has been acquired to define criteria to appropriately evaluate and manage the change for the specific product concerned; A detailed description of the proposed change. The differences with what is already approved should be clearly highlighted (preferably in a tabular format). Depending upon the nature of the change, it should be demonstrated, preferably with data from development or pilot scale studies, that the proposed approach is feasible.
If only lab-scale data are provided the potential scale up effect should be discussed: –
- Risk assessment of the impact of the change on product quality. This should include identification of the potential risks and detailed strategy of how these risks will be mitigated or managed;
- Discussion on the appropriateness of the approved control strategy to identify and manage these risks and, if required, description of the additional controls that might be needed to be put in place. This should take into consideration the extent of the change and therefore the potential impact on the quality of the active substance and/or finished product, as appropriate;
- Description of the studies to be performed, and the test methods and acceptance criteria that will be used to fully assess the effect of the proposed change on product quality1. The applicant should justify the appropriateness of the methods proposed to assess the impact of the proposed change. Data from development or pilot scale studies can provide assurance about the relevance and adequacy of the proposed tests;
- For biologics, the approach to be used to demonstrate the comparability of the pre-and post-change product;
- A plan for stability studies should be included, if appropriate;
- Commitment to update the approved protocol, if this becomes invalid, due to significant changes to the proposed test methods/acceptance criteria or a significant body of new knowledge or new regulatory requirements;
- In case that the protocol describes several changes, a justification showing that how the changes are related, and that a simultaneous review under a single protocol is meaningful;
- For chemical medicinal products, a proposal of how the implementation of the change will be reported to the relevant competent authorities using the existing variation procedures;
- For biological medicinal products, in accordance with the Variations Classification Guideline.
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