SOP Title: CHANGE CONTROL PROCEDURE

OBJECTIVE

To define the procedure for controlling and documenting changes using a systematic approach that ensures evaluation of their potential impact on product quality and the overall Quality Management System (QMS).

SCOPE

This SOP is applicable to all changes related to systems, processes, methods, procedures, products, materials, facilities, equipment, utilities, and documents.

RESPONSIBILITY

Change Initiator / Owner

Responsible for:

• Defining, discussing, and documenting the objectives, scope, and deliverables of the proposed change in coordination with stakeholders and QA.
• Initiating and requesting change control.
• Managing the change control record and coordinating implementation.
• Assessing potential risks and impacts with QA and cross-functional teams.
• Identifying required action items for execution.
• Managing timely implementation in collaboration with all relevant stakeholders.
• Requesting progress updates and resolving issues during execution.
• Coordinating change control extension, if required.

Change Initiator’s Department Head / Designee

• Reviews the Change Control Record (CCR).
• Ensures coordination and execution of the change within the department.

Quality Assurance (QA)

Responsible for:

• Issuance of the Change Control Form.
• Reviewing the change proposal and assigning the Change Control Number (CCN).
• Logging the change in the Change Control Log.
• Reviewing proposed changes for:
  • Risk and impact on product quality.
  • Regulatory commitments and audit implications.
  • Categorizing the change appropriately.
• Identifying stakeholder departments for review and action planning.
• Reviewing implementation status.
• Defining and verifying effectiveness criteria for the change.
• Periodically reviewing open and closed changes.
• Maintaining, archiving, and retrieving change control documentation per SOP on document retention.
• Performing trend analysis on change controls.
• Verifying closure of the change control after implementation.
• Commenting on the impact of delays in implementation.

Cross-Functional Team

• Reviews change proposal and justification.
• Conducts risk and impact assessments, if applicable.
• Recommends action items for execution, as needed.

Site Operation Head / Designee

• Reviews and provides comments on change controls.
• Approves change control extensions where applicable.

Head – Regulatory Affairs (RA) / Designee

• Reviews the proposed change for regulatory impact.
• Comments on:
  • Need for regulatory filings or notifications.
  • Customer communication and documentation requirements.

Site Quality / QA Head / Designee

• Reviews the Change Control Record.
• Approves or rejects the CCR based on its site-wide impact.
• Approves extensions of change control timelines.

Corporate Quality Assurance (CQA)

Responsible for:

• Managing corporate-level change controls, including:
  • Issuance, evaluation, completion, retrieval, and archival.
• Reviewing quality system changes that apply to multiple sites.

DEFINITIONS

PROCEDURE

Types of Change Controls

There are two primary types of change controls:

• Temporary Change Control
• Permanent Change Control

Temporary Change Control

• Planned for a fixed number of batches, time period, or specific condition.
• Implemented to allow studies, data generation, experimentation, or developmental evaluation.
• Must include:
  • Risk Assessment (RA)
  • Impact Assessment (IA)
• Temporary changes are reversible and should not be used as a method to repeatedly bypass standard procedures.
• If results are favorable, the temporary change may be converted into a permanent change with appropriate evaluation and approval from QA.

Evaluation of Temporary Change

• Batches manufactured under temporary change must be assessed for:
  • Compliance with standard specifications.
  • Additional quality attributes (if required by the evaluation committee).
• Batch disposition must comply with the Quality/Technical Agreement with the customer.
• Outcome of OOS investigations or batch disposition decisions may require formal change control initiation.

Conversion of Temporary to Permanent

• Upon satisfactory evaluation, a new permanent change control record shall be initiated.
• Approval is required from the Head QA / CQA Head / Designee.

Permanent Change

• Changes implemented with no intent to revert.
• Effective from a defined date and become part of standard procedures/documents.

Change Review

• QA (in collaboration with the Cross-Functional Team) shall:
  • Review current practices and proposed changes.
  • Assess scientific justification and supporting data.
  • Identify all impacted areas/departments.

Customer/Regulatory Communication

• RA department decides on the need for customer/regulatory notification for permanent changes, in line with applicable regulatory guidelines.

Classification of Changes

• Classification is based on risk evaluation:
  • Major Change: When the associated risk is high (e.g., impact on quality, safety, or regulatory status).
  • Minor Change: When the associated risk is medium or low.

This classification helps prioritize review, approval, and implementation activities.

Minor Changes

Definition:

Minor changes are those unlikely to have any detectable impact on product quality or performance and do not affect critical quality attributes (CQAs) of the product. These may involve no adverse effect on the Quality Management System.

Examples of Minor Changes:

Major Changes

Definition:

Major changes are those likely to significantly affect product quality, performance, data integrity, or patient safety. These often impact CQAs of API and may require regulatory notification or prior approval.

Examples of Major Changes (Not Limited To):

• ±10% change in validated batch size.
• Change in primary packaging material.
• Change in solvents in the final stage.
• Change in KSM/Raw Material/vendor.
• Change in analytical technique.
• Change in shelf-life.
• Equipment replacement (different type).
• Introduction of new product or facility.

List of Major Changes and Required Actions:

Change Control Initiation – Departmental Responsibility

Revalidation Considerations for Changes

When Revalidation May Be Required (Based on Risk Assessment):

• Master formula or method modifications.
• Changes in raw material vendor or manufacturing process.
• Equipment or instrument changes (e.g., adding auto detection systems).
• Layout or water system modifications.
• Process changes (e.g., mixing time, drying temp).
• Site transfers for manufacturing.
• Unexpected changes discovered during self-inspections or trend analysis.
• Changes in cleaning procedures or methods.

QA is responsible for evaluating whether revalidation is required and defining the scope of revalidation activities, including protocol, execution, and reporting.

Change Control Process

Change Control Form Requisition

 The Change Owner shall identify the triggering factor for the proposed change, such as:

• Need for upgrade, improvement, correction, or enhancement.
• Signals from CAPA, Deviation, Complaint, APQR, or Compliance Needs.

The change objective, scope, outcome, and benefits must be discussed with:

• Department Heads
• Key Stakeholders
• Subject Matter Experts (SMEs)
• QA / CQA
• Regulatory Affairs
• Management

Change initiator shall request a Change Control Record (CCR) from QA (Annexure).
Note: Change must be approved within 60 days of issuance. If not, QA must cancel it with a justification and update the CCR log.

QA shall issue the CCR with a stamp, signature, and date. The form will be handed over to the change initiator for filling.

Additional pages can be attached for multi-site changes or if extra space is needed.

Allocation of Change Control Number

QA verifies Part-A(I) and then assigns the change number and logs it in the Change Control Log (Annexure).

Maintain separate logs for:

• Temporary and Permanent change controls.
• Product-specific and General change controls.

Format for Change Control Number:

Format: PXAABBCDDD

5.5.3 Corporate QA Change Control

• CQA manages change controls related to corporate systems: issuance, evaluation, completion, and archiving.
• Changes affecting common quality systems must be evaluated by CQA.

Initiation of Change Control (CCR Part-A)

Part-A(I) – Initiation Details

Filled by the Change Owner in coordination with QA:

• Type: Temporary or Permanent
• Category: Product or General
• Change Description
• Reference Numbers (CAPA/Deviation/Complaint etc.)
• Initiator details

Part-A(II) – Change Details

• Current status
• Proposed change
• Justification
• For Temporary Change, also mention:
  • Number of batches
  • Time period
  • Batch numbers

Initiator must check applicable reasons for the change.

• Include names, signatures, and dates of both the initiator and HOD/designee.

Change Impact Evaluation (CCR Part-B)

QA reviews Part-A and identifies potential impacts and affected systems.

Impact Areas to Evaluate (not limited to):

• Product/Manufacturing Process
• Master Documents (BMR, BPR, Validation Protocols)
• RM/PM/Approved Vendor List
• Stability Study Requirement
• Specifications, STPs, Analytical Methods
• Comparative Product Study
• Process Validation/Revalidation Requirements
• Qualification, VMP, SMF, SAP
• Regulatory/Customer Notification
• Facility/Layout/Drawings
• SOP Revisions
• Required Trainings
• EHS Considerations
• Quality Risk Assessment (QRA)

Risk assessment must follow the respective SOP and be completed before CCR approval.

Functional Review of Change Proposal (CCR Part-C)

Cross-Functional Review Team Includes:

• Production
• QC / QA / CQA
• R&D
• Engineering / WH
• Validation / AMV / Microbiology / AQA
• IT / BS / EHS
• RA / Marketing / Procurement / HR

Note: EHS must review any GMP-related changes impacting facility, process, or safety (excluding QMS SOP/document-only changes).

Change Owner coordinates with stakeholders for comments.

• Stakeholder SME must review and provide:
  • Feasibility
  • Impact
  • Required actions
  • Supporting documents
• Site Head / Designee evaluates high-impact changes (product, facility, SOPs).

If “N/A” is marked for regulatory or customer intimation, a justification must be provided.

Customer Intimation

Customer intimation is based on:

• Technical Agreement
• Regulatory Requirement
• Type of Change

Identification of Actions for Change Implementation (CCR Part-D)

The risk assessment outcome and risk level (Minor/Major) shall guide the:

• Planning
• Prioritization
• Implementation
• Timeline setting

After reviewing cross-functional comments, the Change Owner, in consultation with QA, will finalize and list the sequential action items for implementation.

Each action shall be assigned a:

• Responsible person
• Target completion timeline

The overall change control closure timeline must align with these dates.

The CCR target closure date shall be mutually agreed upon by QA and the relevant department based on action timelines.

QA shall verify the listed actions before implementation begins.

Change Control Approval (CCR Part-E)

The Change Owner must ensure:

• All supporting documentation is attached (e.g., stakeholder checklists, risk assessments).
• CCR is submitted for approval to QA.

Site QA Head or Designee shall review:

• Adequacy of change evaluation
• EHS and regulatory impact
• Resource availability
• Change classification (Major or Minor)

The QA authority shall approve or reject the CCR with a documented rationale.
Customer notification/approval shall follow Technical Agreement terms and be documented in Annexure.

Customer Communication Classification:

Note: Attach email communications if formal Annexure is not approved by the customer.

Change Execution (CCR Part-F)

Responsible persons shall execute the assigned actions. Short descriptions of completed actions must be recorded in Part-F of CCR.

Attachments required in CCR include (but not limited to):

• Reference documents
• Action completion evidence
• Risk assessment report
• Impact evaluation forms (EHS, RA, Engineering)
• CCR source QMS documents

 Verification of Change Implementation (CCR Part-G)

• The Change Owner and Department Head shall confirm full implementation of all actions listed.

Verification & Closure of Change Control (CCR Part-H)

QA shall confirm:

• Objectives and effectiveness criteria are met
• Deviations, if any, are justified and addressed
• Residual risks are mitigated
• Post-implementation actions or CAPAs (if needed) are completed

QA shall determine if ongoing monitoring or protocol-based evaluation (e.g., via APR, trend analysis) is required.

If effectiveness evaluation is unsatisfactory, the CCR shall be:

• Re-evaluated by QA
• Closed with CAPA
• Reopened or a new CCR initiated if necessary

If successful:

• CCR shall be closed
• QA Head or Designee shall approve the closure

Change Control Extension

Extension Limits:

• Maximum 2 extensions allowed
• Approvals as per Annexure:

Note: If CCR remains incomplete after 2nd extension:

• A new change control must be initiated
• The old CCR shall be closed by referencing the new one
• Impact of delay must be assessed

Delay in Change Implementation

• The Change Owner/Designee must:
  • Justify the delay
  • Complete an extension form (Annexure)
  • Document practical and logical reasons for the delay

Trend Analysis of Change Control

Site QA shall conduct a trend analysis of change controls annually.

Trend analysis shall be based on, but not limited to, the following parameters:

Any adverse trends shall be identified, and corrective/preventive actions initiated as needed.

Note: Trending is not required for CCRs initiated by CQA for corporate-level quality systems or facility changes that do not affect product quality.

Handling of Additional Sheets for Documentation

If the space provided in any Annexure is insufficient, the following guidelines shall be followed:

• Use separate sheets/pages with cross-references to the original annexure.
• Each additional page must be signed and dated by the preparer.
• Pages must be securely attached to the main document.
• Additional pages of annexures may be issued as required.

REFERENCES

ABBREVIATIONS