Experiment No.
1 Date:
CASE STUDIES ON CHANGE MANAGEMENT / CHANGE CONTROL DEVIATIONS
FOR SOP, EQUIPMENT AND PROCESS
AIM: To prepare and submit case studies on change management / change control, deviations
for SOP, Equipment and process.
INTRODUCTION:
Definition of Change Management / Change Control
Change Management (or Change Control) is a formal process used in the pharmaceutical
industry to ensure that any planned or unplanned changes to a product, process, system,
equipment, facility, or document are evaluated, approved, implemented, and documented
systematically while ensuring continued product quality, regulatory compliance, and patient
safety.
Types of Changes
1. Minor Change: Does not impact product quality or regulatory filings.
2. Major Change: May affect product quality, requires thorough evaluation, sometimes
regulatory approval.
3. Regulatory Change: Must be reported to or approved by regulatory agencies (e.g., FDA,
EMA).
Objectives of Change Control
Prevent unintended consequences of change.
Maintain compliance with GMPand regulatory expectations.
Ensure continued control over critical processes.
Maintain product integrity and patient safety.
Benefits of an Effective Change Control Process
Benefit Explanation
Controls risk associated with changes in
1. Ensures product quality
manufacturing or testing processes.
Ensures changes are managed in accordance
2. Regulatory compliance
with GMP, ICH q10, ISO, etc.
Prevents issues that could arise from poorly
3. Reduces risk of failures/recalls
evaluated or undocumented changes.
Supports updates in technology, process
4. Facilitates continuous improvement
optimization, or facility upgrades.
Maintains clear records of changes, approvals,
5. Enables traceability & accountability
justifications, and ownership.
G. PULLAREDDY COLLEGE OF PHARMACY REGULATORY AFFAIRS PAGE NO.
Demonstrates a robust quality system to
6. Supports audit & inspection readiness
regulatory inspectors and auditors.
Requires involvement from QA, production,
7. Enhances cross-functional collaboration
engineering, regulatory, etc.
Key components of a change management system
Component Description
Initiation of change by authorized personnel,
Change request (CR)
including detailed justification.
Multidisciplinary evaluation of potential
Impact assessment
impacts on quality, safety, and compliance.
Use of tools like FMEA, risk matrix to assess
Risk assessment
risks and mitigation plans.
QA, regulatory affairs, and relevant departments
Approval process
must review and approve.
Timeline, responsible persons, resources, and
Implementation plan
training requirements are defined.
Ensure change performs as expected without
Verification/validation
adverse effect on product.
All changes and evaluations are documented for
Documentation
traceability.
Once implemented and verified, QA formally
Closure
closes the change.
Assess effectiveness and look for unintended
Post-implementation review
consequences.
ICH Q10 (Pharmaceutical Quality System) on Change Management
According to ICH Q10, a pharmaceutical company must:
Use a formal change management system.
Ensure evaluation and authorization by a quality unit.
Assess changes based on scientific risk management.
Ensure ongoing product quality and process performance.
Example Changes Requiring Change Control
Change in raw material vendor.
Equipment replacement or modification.
Change in testing method or specification.
Facility layout modification.
G. PULLAREDDY COLLEGE OF PHARMACY REGULATORY AFFAIRS PAGE NO.
Change in manufacturing process.
Update in sops or Batch Manufacturing Records.
Software or system updates (e.g., LIMS, ERP).
Change in cleaning procedure or cleaning agents.
Tools Used in Change Management
Change Control Forms / Templates.
FMEA (Failure Modes and Effects Analysis).
Risk Matrix.
Deviation and CAPA Systems Integration.
Electronic Quality Management Systems (EQMS).
Case Study 1: Change Control in SOP (Standard Operating Procedures)
Company: Wintac Limited.
Source: US FDA Warning Letter MARCS-CMS 605369.
Date: March 13, 2019.
PROBLEM:
Uncontrolled and poorly assessed changes to critical sops affecting aseptic manufacturing
practices, without following proper change control procedures.
ISSUES IDENTIFIED BY FDA:
1. Sops revised without QA approval (e.g., gown reuse in cleanrooms).
2. No risk assessment done to evaluate the impact on product quality.
3. Lack of staff retraining on the updated sops.
4. Microbial contamination incidents traced back to procedural changes.
5. No documentation or tracking of SOP versions in use.
6. Inadequate change control system, lacking cross-functional review.
SOLUTIONS IMPLEMENTED:
1. Reinstated original sops until proper assessment of new versions.
2. Performed comprehensive impact assessment on all SOP changes from the last 12
months.
3. Introduced a revised Change Control SOP:
o Mandatory QA approval before changes.
o Impact and risk assessment form required.
o No SOP goes live without verified training records.
4. Installed Document Management System (DMS) with version control.
G. PULLAREDDY COLLEGE OF PHARMACY REGULATORY AFFAIRS PAGE NO.
5. Hired third-party GMP consultant for system-wide audit and remediation.
6. Periodic internal audits to ensure sustained compliance.
Case Study 2: Change Control in Equipment
Company: Lec Custom Products Inc.
Warning Letter Date: September 2020
Facility: Ontario, Canada
Source: FDA Warning Letter
Background:
Lec made modifications to their tablet compression machine (new die parts and mechanical
alignment changes) without proper validation and documentation under change control.
Observations:
Equipment changes were implemented without requalification.
Compression force variations resulted in under-dosed tablets.
Change was not logged in their equipment change control log.
Problem:
Improper product weight due to unqualified changes to compression force control settings.
Corrective Action:
Revalidation of all impacted equipment with documented change control.
Revised sops to require QA review for all mechanical modifications.
Implemented a preventive maintenance and change tracking system integrated with
CAPA.
Case Study 3: Change Control in Process
Company: Mylan Laboratories Ltd. – Unit 7
Warning Letter Date: August 2020
Facility: Pashamylaram, India
Source: FDA Warning Letter
Background:
Mylan modified their solvent recovery and reuse process for APIs without comprehensive
evaluation of cross-contamination risks.
Observations:
Unknown impurities found in recovered solvents used across multiple API lines.
Inadequate cleaning validation of multi-use storage tanks.
No process validation or impurity profiling post-change.
G. PULLAREDDY COLLEGE OF PHARMACY REGULATORY AFFAIRS PAGE NO.
Problem:
Failure to evaluate impact of recovered solvent purity led to potential cross-contamination in
APIs.
Corrective Action:
Suspended use of all solvent batches from affected CMO.
Implemented impurity profiling and change impact assessments for all process changes.
Engaged third-party consultants for retrospective risk analysis and global SOP
harmonization.
REFERENCES:
Https://database.ich.org/sites/default/files/Q10%20Guideline.pdf [Accessed- 26-06-2025]
Deviation
Https://www.mastercontrol.com.0./gxp-lifeline/change-in-pharmaceutical-manufacture/
#:~:text=Change%20Control%20Process%20in%20the,%2C%20efficacy%2C
%20quality%20or%20compliance.[Accessed- 26-06-2025]
Warning letter available from
1 Wintac Limited
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/
warning-letters/wintac-limited-606700-08132020?Utm_source=chatgpt.com
2 Lec Custom Products
Https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/
warning-letters/lec-custom-products-inc-607838-09242020
3 Mylan Laboratories Ltd https://www.fda.gov/inspections-compliance-enforcement-and-
criminal-investigations/warning-letters/mylan-laboratories-limited-unit-7-607508-
08202020
[Accessed- 26-06-2025]
REPORT:
G. PULLAREDDY COLLEGE OF PHARMACY REGULATORY AFFAIRS PAGE NO.
