Change Control Procedure in Pharmaceuticals

By: Pharma Tips | Views: 64111 | Date: 26-Aug-2013

Change control is a CGMP concept that focuses on managing change to prevent unintended consequences. Certain manufacturing changes (i.e changes that alter specifications, a critical product attribute or bioavailability) require regulatory filings and prior regulatory approval.Change is an inherent part of the life cycle of a pharmaceutical product. A change can be an addition to, deletion of, or modification to manufacturing facility, utilities, process, material, product, procedures or equipment (including

Change Control Procedure in Pharmaceuticals

Change Control Procedure in Pharmaceuticals

 
Change Control System

Change control is a CGMP concept that focuses on managing change to prevent unintended consequences. Certain manufacturing changes (i.e changes that alter specifications, a critical product attribute or bioavailability) require regulatory filings and prior regulatory approval.
Change is an inherent part of the life cycle of a pharmaceutical product. A change can be an addition to, deletion of, or modification to manufacturing facility, utilities, process, material, product, procedures or equipment (including software) which impacts quality or regulatory requirements.



Change control is a procedure that ensures changes are implemented in a controlled and coordinated manner. The  change control program evaluate all changes that could affect the production and control of the drug product, intermediate or API. It is the most critical element in the overall quality management of pharmaceutical industry. A change control system provides checks and balances in the quality system by tracking, reviewing and approving the changes. In adequate change control procedures ends up in regulatory non compliance.

The purpose of change control is to prevent the unintended consequences that are sometimes encountered when making a change to a product or system.

Benefits of change control system
  • Structured and systematic approach for change management with proper change evaluation
  • Documenting & tracking  the details of change
  • Routing of change requests to appropriate individuals/team for approvals
  • Demonstrate compliance to regulatory agencies

Change control Process flow
Changes can happen anytime during a product’s  life cycle.
 
 
Change proposal
 

 
 
Change Evaluation/review
 

 
 
Change Classification
 

 
 
Identification of impacted systems/documents & risk assessment
 
 

 
Change Approval
 
 

 
Change implementation
 

 
 
Verification of change implementation
 

 
 
Change control close out
 


Change control Procedure
A formal change control procedure always begins with a change proposal, which is initiated by user department personnel with proper justification. The change proposal then, evaluated by an expert team (change control committee) contributing the appropriate expertise and knowledge from relevant areas.

After change evaluation, quality unit will classify the change (i.e minor/major/critical).Benefits of change classification includes

v Classification can help in assessing the impact of change in a reliable way.

v Change classification can be used to identify risk associated with each change request.

v Change classification can help to determine the change acceptability (i.e reject or approve changes).

Change classification triggers impact analysis of the proposed change for identification of impacted systems and documents. There are several risk associated with each change proposal, including  reduced product quality. Risk assessment in changing requirements of existing systems is an important aspect of producing the desired result of a change.

After impact analysis and risk reduction, quality unit will approve or reject the change proposal based on the criticality of the proposed change. The change can be implemented after change approval by quality unit. After implementation, quality unit verify the effectiveness of implemented changes, to confirm the change objectives were achieved and that there was no deleterious impact on product quality. After verification of change implementation, the change control can be closed.

Change control procedure should ensure that the level of documentation and effort is matched to the risk associated with the change. It should be ensured that

v The change control is linked to other quality system such as CAPA, customer complaints, validation etc.

v Includes criteria to evaluate whether changes affects regulatory filings.

v Includes evaluation criteria for determining if changes are technically justified.

GMP deficiencies related to change control
v Inadequate review & approval of the change by quality control unit.

v Failure to file the changes with regulatory.

v Failure to evaluate/justify the changes.

v Excluding "like-for-like" changes from change control program.

Change controls for like to like changes
‘Like to like’ change – replacement of a piece of equipment by another with ideal characteristics and function.
A pump on a spray dryer system must be managed to control product flow rate to the dryer. Because the product is sensitive to even minor changes in this rate, the pump is considered a critical element of the process. The pump recently failed. A new pump of the same model, same manufacturer and same design was purchased to replace it --- a like-for-like change. However, the new pump operates more efficiently than the "old" pump and generates 10% higher RPMs than the old one. Thus, product flow rate (i.e, injection pressure) is different and results in failing particle size distribution of the final product.

Let us consider another example of like-for-like change
A company performed a routine replacement of the filling pump pistons, without taking a change request because it was a “like to like” replacement (which has been a typical industry practice). Although the replacement pistons had the same part number as the original pistons, they were slightly longer. This longer dimension caused the pistons to come into contact with the bottom of the filling blocks, resulting in the generation of metal particles, which contaminated the product batches.This metal contamination resulted in the recall of several product batches.

In both the case, a like-for-like change impacted product quality. Thus, even for like-for like changes, an assessment is needed to determine if pre-use testing, assessment,qualification or other verification is needed before use. In short, some truly like-for like changes are innocuous and should be implemented without change control assessment. BUT, equipment, processes or controls that could impact product quality should receive additional scrutiny prior to use.



Standard Operating Procedure for Change Control

1.0 Purpose : To provide instruction for change control procedure.

2.0 Objective : To provide a documented procedure for change control procedure.

3.0 Scope : This procedure is applicable for change control procedure.

4.0 Responsibility :
Primary: Officer / Supervisor of respective department.
Overall: Respective department Head.

5.0 Procedure :
• Components of change control
Following changes are including in change control procedure.
Change in the storage condition of raw material, finished goods, WIP.
Change in Expiry or retest date.
Change in Stability study protocol.
Change in SOP.
Change in protocol.
Change in Batch Manufacturing Record.
Change in Batch Packing Record.
Change in Specification and Analytical Test Method of following:
Raw materials and Packaging materials.
In process and Intermediates.
Finished Products.
Change in drawings.
Change in Utilities.
Change in Manufacturing process including rework and re-processing.
In process controls.


• Change Control Procedure.


Any of the changes excluding the changes in specifications, analytical methods, Master Formula, Batch Manufacturing Records and those changes affecting the regulatory affairs shall be controlled by the corporate QA.

Any changes at related to GMP requirements but not directly related to manufacturing or testing process shall be controlled through Ankleshwar QA.

The person requesting the change should fill in the ‘Change Control form’ and submit it to QA In charge through the department head.

The person requesting the change shall add any reasons or justification with adequate supporting data for the change to the ‘Change Control form”.
 
The Q. A In charge shall evaluate the change proposal considering the necessity for change and any other GMP aspects that will be affected by the proposed change. If the Q.A In charge has the valid reasons to reject the proposal for change, he / she can reject the change proposal and intimate the requester about the same.

The Q.A In charge shall verify the proposed change by a number of factors

If required the Q.A In charge shall direct the changes to Corporate QA

If the supporting data is not sufficient, he / she shall direct the requester or any other related departments e.g. Quality Control to generate the specified information or data.

The Q.A In charge shall approve the change and shall forward the request to corporate QA for their evaluation & suggestions if required.

If proposed change is in the purview of Corporate QA, The QA In charge shall forward the change control form with his/ her remark or suggestions to the corporate QA. QA personnel shall coordinate with corporate QA for the proposed change.
Once the QA department approves the change control form, the user department shall prepare relevant revised documents.
The revised document shall be approved by QA in charge.
User department shall implement the change, based on effective date mentioned on the documents.

NOTE: For any proposed change it is necessary to confirm that, the proposed change will not violet the statutory requirements. If it is require to inform to statutory authority of the concern country or to the concern buyer, it is necessary to first get approval from statutory authority of the concern country or from the buyer, than only proposed change shall be implemented.


6.0 Reference Document :

Change Control Form
Change Control logbook

LOG BOOK FOR CHANGE CONTROL

Sr. No. Change
Control
No. Document No. Revision No. Description of Change Reason for Change Effective date Signature of
QA Remarks

7.0 Abbreviations:
• QA = Quality Assurance department
• SOP = Standard Operating Procedure
• WIP = Work In Progress
• GMP = Good Manufacturing Practices
• CCF = Change Control Format

8.0 Copies to Distribution Sites
• QA –Ankleshwar
• QC- Ankleshwar
• Stores – Ankleshwar
• Production – Ankleshwar
• Engineering – Ankleshwar
• Personnel & Administration – Ankleshwar

9.0 Review History :

Sr. No. Previous
Revision No. New
Rev. No. Review Date Reason For
Review Change
Control
No. Approved
By


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Comments
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