Change Control in Pharma: Definition, Types, Process, and Regulatory Requirements

Change control in the pharmaceutical industry refers to a structured, documented process that manages any modifications to systems, processes, materials, equipment, or documentation that could impact product quality, safety, or regulatory compliance. The main objective of change control is to maintain control over pharmaceutical operations, ensure patient safety, and uphold product quality.

Change control is important in the pharmaceutical industry because it ensures that modifications are thoroughly assessed before implementation and do not introduce unintended or unmanaged risks to processes.

Change controls in the pharmaceutical industry are categorized based on their severity, schedule, permanency, and domain.

The change control process involves a series of formalized steps, including initiating a change request, performing an impact assessment, determining an implementation plan, reviewing and approving the change package, completing pre-implementation activities, providing training to affected staff, implementing the change, and verifying the effectiveness of the change.

Different regulatory frameworks, including EudraLex Volume 4 and FDA 21 CFR Part 211, provide specific expectations for managing changes in Good Manufacturing Practices (GMP) related processes. ICH Q10 integrates change control into a broader pharmaceutical quality system model, while ICH Q7 extends change control requirements to Active Pharmaceutical Ingredients (APIs) manufacturing.

Efficient change control management in the pharmaceutical sector depends on having a clearly defined, cross-functionally executed process supported by thorough documentation and risk assessment. Best practices in change management include integrating change control with Quality Management System (QMS), as well as leveraging technology.

SimplerQMS offers a cloud-based, fully validated electronic Quality Management System (eQMS) that streamlines the change control process. SimplerQMS change management module enables end-to-end tracking with built-in workflows and compliant electronic signatures. SimplerQMS supports many quality processes, making it a comprehensive solution for pharmaceutical companies aiming to optimize change control processes while maintaining regulatory compliance and audit readiness.

What Is Change Control in the Pharmaceutical Industry?

Change control in the pharmaceutical industry is a systematic, documented process used to manage, evaluate, approve, and record modifications to processes, systems, equipment, materials, or documentation that could affect product quality, safety, or regulatory compliance. Change control ensures that all proposed changes are assessed before implementation, executed in a controlled, compliant manner, and verified for effectiveness afterward.

Change control is mandated by multiple pharmaceutical regulatory frameworks, with the most explicit change control definitions provided in ICH Q10, EudraLex Volume 4 in Annex 15, and PIC/S GMP. ICH Q10 defines change management as a systematic approach to proposing, evaluating, approving, implementing, and reviewing changes, ensuring they are managed in a controlled manner throughout the product lifecycle.

EudraLex Volume 4, or EU GMP, in Annex 15 defines change control as 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. Change control aims to determine the actions required to ensure and document that systems remain validated. PIC/S GMP in Annex 15 uses the same definition as EU GMP.

The objective of implementing change control in pharmaceutical manufacturing and quality systems is to maintain control over processes, systems, and equipment throughout their lifecycle. Change control minimizes risks associated with uncontrolled modifications, protecting patient safety and ensuring product quality. The change control process also establishes formal documentation and traceability, supporting transparency and inspection readiness.

Why Is Change Control Important in Pharma?

Change control in the pharmaceutical industry is important because it ensures that any modification is managed in a controlled, documented, and compliant manner.

The key benefits of the change control process within the pharmaceutical industry are the following.

• Ensures Patient Safety and Product Quality: Change control ensures that modifications do not negatively impact product safety, efficacy, or quality. Each change is assessed before implementation to confirm continued compliance with defined product specifications.
• Maintains Regulatory Compliance: Change control ensures alignment with GMP requirements set by authorities such as the FDA and EMA. Proper change documentation and approval workflows demonstrate to inspectors that the company maintains oversight of changes.
• Facilitates Risk Management: Change control integrates risk assessment by identifying potential quality or compliance risks before changes occur. This proactive impact evaluation prevents uncontrolled risks.
• Improves Operational Efficiency: A structured change control process minimizes disruptions, reduces rework, and maintains production continuity. Change control process standardizes evaluation and approval steps, leading to faster, more predictable outcomes.
• Strengthens Communication and Collaboration: Change control formalizes communication across departments such as quality assurance, production, quality control, and regulatory affairs.
• Facilitates Knowledge Management: Documented change records create traceable information that supports future decision-making, training, and audits. The change control process ensures that organizational knowledge about processes and modifications is preserved.
• Supports Continuous Improvement: Change control enables systematic review of processes, equipment, and systems when modifications are introduced.

When Is Change Control Required in Pharma?

Change control is required in the pharmaceutical industry whenever a proposed modification could potentially impact product quality, safety, efficacy, regulatory compliance, or process reproducibility. Change management applies to any modification that may affect the validated or qualified state of equipment, systems, processes, facilities, or materials. Examples of changes that require a formal change control include changes in raw material suppliers, manufacturing parameters, testing methods, packaging components, cleaning procedures, or software used in GMP environments, among others.

A formal change control is not required for activities that fall within routine, pre-approved operations or actions that do not affect the validated or qualified state. Change control is not required in activities governed by pre-approved protocols, standard operating procedures, or work instructions where the scope and limits of variation are already defined. “Like-for-like” replacements of components with identical specifications do not require change control. Document revisions that have no impact on GMP or product quality, like typo error corrections, can proceed without initiating formal change control.

What Is the Relationship Between Change Control, Deviations, and CAPA?

Change control, deviations, and Corrective Actions Preventive Actions (CAPA) are interconnected processes of the pharmaceutical quality system that collectively ensure product quality and safety. Change control manages any planned modification. Deviations document and investigate unplanned quality issues, nonconformances, or departures from approved procedures or specifications. CAPA identifies and addresses the root cause of deviations, audit findings, or other quality issues to prevent recurrence.

The relationship between change control, deviation, and CAPA processes is complementary. A deviation may trigger a CAPA to eliminate the root cause, and the CAPA outcome may result in a modification requiring a formal change control. Together, change control, deviation, and corrective and preventive actions processes create a strong QMS foundation, supporting pharmaceutical companies to maintain control over their operations, address unexpected quality issues promptly, and implement improvements systematically.

What Are the Different Types of Changes in Pharma?

Changes in the pharmaceutical industry are classified into four different categories based on the change’s severity, schedule, permanency, and impacted domain.

The different types of changes in the pharmaceutical industry are the following.

• Based on Severity: Changes categorized by severity are usually classified as minor, major, or critical. Critical changes may be a subset of major changes. As referenced in ICH Q7, the classification reflects the nature and extent of the change, as well as the potential impact on the affected processes.
• Based on Schedule: Changes categorized based on schedule include planned and unplanned changes. Planned changes are introduced deliberately under full control, while unplanned changes occur unexpectedly. Unplanned changes may require investigation as deviations to determine their root cause and impact.
• Based on Permanency: Changes categorized based on their permanency are identified as temporary or permanent. Temporary changes are implemented for a limited, predefined duration, while permanent changes modify the process, system, or documentation on a long-term basis.
• Based on Domain: Changes are categorized based on their domain of impact, such as materials, processes, equipment, facilities, or documents. Regulatory expectations for domain-specific changes are outlined in both FDA 21 CFR Part 211 and EU GMP.

Types of Changes Based On Severity

Changes are classified by severity based on their potential impact on product quality, patient safety, and regulatory compliance. Severity classification determines the level of evaluation, documentation, and regulatory notification required before implementation.

Below are listed the most typical severity classifications of changes.

• Minor Changes: Minor changes have little or no impact on product quality, process performance, or regulatory compliance. An example of a minor change is an update to a manufacturing site address resulting from a municipal renumbering, without any physical relocation of the facility. Although the change of municipal renumbering does not affect operations or quality, authorities may need to be notified because the site address appears in the GMP certificate and manufacturing authorization. Related parts of product dossiers, such as Module 3, may require updates. Minor changes usually require Type IA variations in the EU or annual reporting in the US, and in some cases, no variation at all.
• Major Changes: Major changes may affect product quality, process performance, or compliance and require formal regulatory submission and further studies. An example of a major change is the introduction of a new API supplier who holds equivalent qualifications and certification status as the existing one, such as a CEP-supported supplier with demonstrated equivalence in quality and GMP compliance. Major changes typically require variations that must be submitted, and in some cases approved, before implementation or before the release of the first batch produced under the new conditions. Major changes may require additional studies, including validation or stability studies.
• Critical Changes: Critical changes have a significant or direct impact on product quality, process performance, or regulatory compliance. An example is the transfer of drug product manufacturing to a new facility. Critical changes require prior review and approval by regulatory authorities before implementation. Critical changes are tightly controlled and supported by extensive studies to ensure that patient safety and product quality remain uncompromised.

Types of Changes Based On Schedule

Changes based on schedule are classified according to whether they are anticipated and controlled or occur unexpectedly during operations. Schedule-related classification determines how the change is documented, reviewed, and managed to ensure continued product quality and compliance.

Planned changes are intentional, pre-approved modifications introduced under controlled conditions. Planned changes are initiated through the formal change control process and implemented only after full assessment, approval, and risk evaluation. Examples of planned changes include scheduled equipment upgrades, manufacturing process optimization, or the introduction of a new analytical method. Planned changes are managed proactively to maintain product quality and compliance and minimize operational risk.

Unplanned changes occur unexpectedly, often due to deviations or equipment failures. Unplanned changes can directly affect product quality, process performance, or regulatory compliance and must be promptly investigated through deviation and CAPA procedures. Examples of unplanned changes include unanticipated raw material shortages or sudden equipment breakdowns, leading to either changes in production planning or even the need for new material or equipment. Pharmaceutical companies must document and investigate unplanned changes to determine their root cause and implement corrective actions to prevent recurrence.

Types of Changes Based On Permanency

Changes based on permanency are classified according to their duration and intended effect on processes, systems, or materials.

Temporary changes are implemented for a limited time to address specific situations or support short-term operational needs. Temporary changes are managed through the change control process, with defined start and end dates, and any associated risks are assessed and controlled. A typical example of a temporary change is using manual bundling of box units in case of the bundling machine breakdown. Once the intended purpose is fulfilled, the process must revert to its original state unless further evaluation leads to permanent adoption.

Permanent changes are long-term modifications that become part of the approved, validated process, system, or documentation. Permanent changes are fully assessed, justified, and, if needed, validated or qualified to confirm that the new condition ensures consistent product quality, process execution, and compliance. Examples of permanent changes include implementing a new manufacturing line, revising an analytical method, or introducing new qualified production equipment.

Types of Changes Based On Domain

Changes based on the domain are classified according to the area of impact within the pharmaceutical quality system. This classification ensures that each change is evaluated using domain-specific requirements and controls to maintain product quality, safety, and regulatory compliance.

The main change categorizations based on the domain of impact are the following.

• Product Changes: Product changes involve modifications to the finished product, formulation, or specifications. Typical examples of product changes are changes to water quantity used in production, an impurity limit, or shelf-life extension. Product changes can directly affect the final product’s quality, stability, and regulatory approval status.
• Process Changes: Process changes refer to modifications to manufacturing or cleaning processes. Examples of process changes include updates to process parameters, introduction of new sterilization methods, or changes in batch size. Depending on their impact, process changes may require revalidation to ensure consistent product quality and compliance with GMP.
• Analytical Method Changes: Analytical method changes involve revisions to testing methods used to assess raw materials, intermediates, or finished products. An example of an analytical method change is the updating of the assay or impurities method. As analytical methods directly impact the accuracy and reliability of quality control testing, any changes must be appropriately justified, validated, and approved before implementation.
• Material Changes: Material changes refer to modifications to raw materials. Some examples of material changes are switching to a new grade of excipient, using an alternative packaging material, or updating a certification, e.g., CEP of an API. Material changes can impact product quality and must undergo thorough evaluation.
• Supplier Changes: Supplier changes occur when introducing or replacing a supplier of materials or services. Examples of supplier changes include adding a new API or an excipient vendor. Supplier changes require supplier qualification and may trigger regulatory notifications depending on the material’s criticality.
• Equipment/Facility Changes: Equipment and facility changes involve modifications to manufacturing or testing equipment, utilities, or physical areas of the facility. Examples include installing new equipment, replacing a purified water system, adding a new production line, or expanding cleanroom areas. Equipment and facility changes may affect environmental control, equipment qualification status, process consistency, and GMP compliance, and thus are typically classified as major or critical.
• Computerized System Changes: A computerized system change refers to updates or replacements of software or hardware used in GMP operations. An example of a computerized system change is implementing a new eQMS, upgrading LIMS, or changing server infrastructure supporting a validated application. Such changes can affect data integrity, system validation status, and regulatory compliance. Depending on the market, computerized system changes may need to comply with FDA 21 CFR Part 11 or EU Annex 11 requirements.
• Documentation Changes: Documentation changes include the creation or update of controlled documents such as SOPs, specifications, batch records, validation master plan, or site master file. Documentation changes must follow formal document control and approval processes before use to ensure procedural consistency.
• Organizational Changes: Organizational changes involve restructuring departments, changing responsibilities, or altering reporting lines. An example of organizational change is introducing a new management role. Organizational changes may affect responsibilities defined in the quality system and must be reflected in updated procedures.
• Regulatory Changes: Regulatory changes occur due to new or updated regulatory requirements impacting operations or product compliance. Examples of regulatory changes include implementing revised GMP guidelines or new pharmacopeia monographs. Pharmaceutical companies must assess, plan, and implement regulatory changes promptly to ensure continued compliance with current regulatory expectations across markets.

What Are the Steps in the Pharmaceutical Change Control Process?

The pharmaceutical change control process describes the systematic evaluation and approval of proposed modifications to processes, systems, equipment, or documentation. The purpose of the change control process is to ensure that all proposed changes, along with their corresponding action plans, are thoroughly reviewed, justified, and authorized before implementation, thereby minimizing the likelihood of unmanaged risks.

The key steps in the pharmaceutical change control process are the following.

1. Initiate Change Request: The process begins with submitting a formal change request that describes the proposed modification and provides a reason and justification for the change.
2. Perform Impact Assessment: The proposed change is assessed by a multidisciplinary team to determine its impact, including potential effects on product quality and safety, process execution, validation status, or regulatory compliance.
3. Determine Implementation Plan: A detailed plan is developed by the change owner outlining required activities, responsibilities, timelines, and resources needed for the implementation of the change.
4. Review and Approve Change Package: The change package undergoes review and approval by relevant department SMEs and/or managers, Regulatory Affairs (as applicable), and QA to ensure the impact of the change has been thoroughly addressed, and all risk mitigation and compliance measures are defined before execution.
5. Complete Pre-implementation Activities: Preparatory steps, such as equipment qualification, document updates, or validation activities, are completed according to the plan.
6. Provide Training (As Applicable): Personnel involved in the modified process or system receive appropriate training to ensure competence in executing new or revised procedures.
7. Implement Change: The approved change is implemented upon completion of all necessary pre-implementation actions in accordance with the approved plan.
8. Verify Change Effectiveness: An effectiveness check is performed to confirm that the change achieved its intended purpose without negatively impacting product quality, process consistency, or compliance.

1. Initiate Change Request

Initiating a change request is the first step in the change control process. Change request initiation clarifies the scope, intent, and justification for the proposed change before any action is taken. At this first step, it is identified whether the proposed change is temporary or permanent, and whether it is planned or unplanned.

A successful change request should clearly explain what will be changed, why the modification is needed, and how it will improve or impact the existing process, system, material, or documentation.

The change owner, typically the process owner, is responsible for initiating the change request and ensuring that all relevant information is captured. QA and Regulatory Affairs (RA) must be involved from the beginning. QA ensures compliance with QMS and GMP requirements, and RA assesses whether the proposed modification affects any approved marketing authorization. Depending on the nature of the change, additional departments, such as production, engineering, quality control, or customer service, are involved. For instance, production and engineering will be involved if new manufacturing equipment or facility modifications are proposed. In some organizations, a change control board may review proposed changes prior to authorizing the opening of a formal change control record.

The primary document required at this stage is the change request form, which records the current state, a detailed explanation of the proposed modification, and a justification for why the change is necessary. The change request form can be completed either in hard copy or electronically, depending on the company’s QMS structure.

ICH Q7, clause 13.12, states that any proposals for GMP-relevant changes should be drafted, reviewed, and approved by the appropriate organizational units.

The expected result of change request initiation is that all departments involved have a clear and shared understanding of what the proposed modification entails and why it is being proposed. This supports an informed and thorough impact assessment.

2. Perform Impact Assessment

Performing an impact assessment is the second step in the pharmaceutical change control process. During impact assessment, the potential risks arising from the proposed change and its effect on existing processes, systems, documents, or products are systematically evaluated.

A successful impact assessment involves forming a cross-functional team composed of SMEs and using a structured, documented checklist to evaluate all affected areas. Risk management tools such as Failure Mode and Effects Analysis (FMEA) or risk ranking matrices may be applied to ensure a comprehensive review.

The impact is determined collaboratively by the department initiating the change, SMEs, QA, and RA. The results of the assessment should be documented in the change request form or in a separate impact assessment form, depending on company procedures. For significant changes, the QA team, relevant SMEs, or the managers of impacted departments review the impact assessment and decide whether to approve, reject, or request more information before proceeding.

According to ICH Q10, paragraph 3.2.3, quality risk management should be applied to evaluate proposed changes with a level of formality appropriate to the level of risk, and changes should be assessed against the marketing authorization and current process understanding. ICH Q7 clause 13.13 emphasizes that the potential impact on product quality should be evaluated and that changes may be classified based on their extent and potential effects.

The expected outcome of the impact assessment is the identification of all potential risks that the proposed change poses to product quality, patient safety, or regulatory compliance. At this stage, the change is typically categorized based on its severity and potential impact using ratings such as critical, major, or minor. The impact assessment informs the development of a robust implementation plan that comprehends necessary mitigation actions and resource requirements.

3. Determine Change Implementation Plan

Determining the change implementation plan is the step where the necessary actions, timelines, and resources required to implement the change are defined. The implementation plan outlines how the approved modification will be carried out while ensuring continued compliance and control.

A successful change implementation plan directly addresses the risks identified during the impact assessment and specifies mitigation measures for each identified risk. It ensures that all pre-implementation and implementation activities are sequenced, clearly assigned, and appropriately resourced.

The plan is usually prepared by the change owner in collaboration with SMEs from impacted departments. The change implementation plan includes specific deliverables, responsible personnel, and deadlines to ensure clarity and accountability.

The change implementation plan and its corresponding actions can be documented either within the change request form or in separate documents, depending on company procedures. In an electronic Quality Management System (eQMS), these deliverables may be created as individual tasks.

The expected deliverable of change implementation planning is a clear and actionable plan that assigns responsibilities and timelines to ensure efficient and compliant execution of the approved change.

4. Review and Approve Change Package

Reviewing and approving the change package ensures that the proposed change can proceed from the planning phase to the implementation phase, without introducing unmanaged or unintended risks, after evaluation from technical, regulatory, and quality perspectives.

A successful review and approval of the change package assesses the complete process, including the impact assessment, implementation plan, deliverables, and dependencies, to confirm that all potential risks have been addressed and that appropriate mitigation and compliance measures are in place.

Reviewers typically include SMEs, Regulatory Affairs (when applicable), and Quality Assurance, while final approval may be granted by the same reviewers and/or department managers and the QA Head.

Documentation of the review and approval process is maintained within the change request form or directly in the eQMS, where electronic signatures capture authorization details. All approvals must comply with data integrity principles, including recording names, titles, dates, and signatures.

EU GMP, Chapter 1, clause 1.4 (xii) requires all planned changes to be prospectively evaluated and approved before implementation, including any required regulatory notifications. ICH Q10 states that the proposed changes should be evaluated by qualified teams contributing the appropriate expertise and knowledge from relevant areas.

The expected outcome is an approved change package with risk assessments and actions officially authorized for execution.

5. Complete Pre-implementation activities

Completing pre-implementation activities is the step where all tasks defined in the approved change implementation plan are executed. These activities ensure that the change is implemented in a controlled, compliant, and risk-based manner.

Successful completion of this step requires all assigned tasks to be performed within the approved timeframes to maintain project continuity and prevent delays. Task owners are responsible for executing and documenting their respective activities.

Pre-implementation activities typically address the risks, dependencies, and requirements identified through the change process, such as documentation updates, validation deliverables, training, testing, and regulatory submissions.

Each completed action must be properly recorded in accordance with company procedures, either in hard copy or electronic format, within the QMS. Documenting the actions’ completion provides traceability and evidence that all planned steps have been completed as intended.

The expected outcome is a set of traceable records demonstrating that all planned activities have been completed as required to support the controlled implementation of the change.

6. Provide Training (As Applicable)

Providing training is a critical step in the change control process when the approved modification affects procedures, systems, equipment, or responsibilities. Training ensures that all personnel affected by the implemented change are adequately informed and competent to perform their tasks under the new or modified conditions. Effective training not only supports GMP compliance but also helps prevent operational errors that could compromise product quality or safety.

Training needs are identified by the change owner in collaboration with relevant SMEs and QA, based on the impact assessment and the approved implementation plan. To successfully complete the training step, all impacted employees must receive training on updated procedures, systems, or equipment before performing related activities. The QA department typically oversees the training process, while supervisors ensure participation and competency verification.

Training completion must be documented according to company procedures, either through signed training records or within the company’s eQMS.

Upon training completion, a fully trained workforce capable of operating in accordance with the revised procedures is expected.

7. Implement Change

Implementing the change is the step where the approved modification is put into effect after all preparatory activities have been completed and formally approved. Change implementation marks the transition from planning to operational use, ensuring that the new or revised process, system, or equipment is introduced under controlled and compliant conditions.

To implement the change successfully, all pre-implementation actions defined in the approved plan must be completed. The change owner is responsible for overseeing the implementation and ensuring adherence to the approved plan and timelines. The change may be released for implementation by the QA department.

Documentation of the completed change, including all related approvals and evidence, must be maintained within the completed change request form, confirming that the change has been executed according to regulatory and company requirements.

The expected result is an implemented change that functions as intended without negatively affecting product quality, safety, or regulatory compliance.

8. Verify Change Effectiveness

Verifying change effectiveness is the final step of the change control process in the pharmaceutical industry. The effectiveness check involves evaluating the implemented change to confirm that the intended objectives were achieved and that no unintended risk has been introduced.

A successful verification requires objective evidence, such as performance data or trend analysis, demonstrating that the change produced the desired outcome. The change owner, in collaboration with the QA department, typically performs this evaluation.

Change effectiveness verification results are usually included in a separate effectiveness assessment, linked to the initial change request form and associated change documentation.

Both EU GMP Chapter 1 and ICH Q10 require the evaluation of implemented changes to confirm that quality objectives were achieved, and no deleterious effects on product quality or the quality system have occurred.

The expected outcome of the change effectiveness check is a documented confirmation that the change is effective. If the intended objectives are not met, corrective actions, additional controls, or further modifications may be required before the change control package can be closed.

What Is a Change Control SOP in the Pharmaceutical Industry?

A change control SOP in the pharmaceutical industry is a controlled document that defines the standardized procedure for initiating, evaluating, approving, implementing, and documenting changes.

The key objective of a change control SOP in the pharmaceutical industry is to provide a structured framework to ensure that all changes are managed in a consistent, traceable, and compliant manner throughout their lifecycle.

The typical components of a change control SOP in the pharmaceutical industry are the following.

• Purpose and Scope: The purpose and scope of an SOP define the intent of the procedure and the areas, systems, or processes to which it applies.
• Responsibilities: The responsibilities section specifies the roles and responsibilities of personnel involved in the change control process, such as change owners, reviewers, SMEs, QA, and Regulatory Affairs.
• Change Identification and Submission: Change identification and submission steps describe how changes are initiated, documented, and submitted for evaluation, usually through a change request form.
• Change Evaluation and Impact Assessment: Change evaluation and impact assessment sections outline the process for assessing risks and determining the potential effect of the change on product quality, process performance, validation, and regulatory compliance.
• Change Implementation Plan Preparation: The change implementation plan preparation section explains how to develop a detailed action plan defining required steps, responsible persons, and timelines.
• Change Package Review and Approval: The implementation package review and approval steps define the review and approval process for the change request, impact analysis, and implementation plan before the change implementation phase.
• Change Actions Closure: Change actions closure step specifies how to confirm that all required actions have been completed and documented.
• Effectiveness Check: The effectiveness check section describes the verification process used to confirm that the change achieved its intended objectives without adverse impact.
• Change Control Forms and Records: In the change control forms and records section, the forms, templates, and records required for documentation and traceability of actions are listed.
• Related Procedures/Related Documents/References: The related procedures section references other SOPs or regulatory documents relevant to the change control process.
• Definitions: The definitions section provides definitions of key terms and abbreviations used within the SOP.
• Appendices: Appendices include supporting materials, such as flowcharts illustrating the change control process.

What Documents and Records Are Used in Change Control in Pharma?

Documents and records used to capture change control activities in the pharmaceutical industry are part of the company’s QMS. Change control records may be maintained in hard copy or electronic format and can be managed manually or through an eQMS.

The essential documents and records for change control in the pharmaceutical industry are listed below.

• Change Request Form: The change request form is the core document of the change control process that records details of the proposed change reason and justification, classification, and required approvals.
• Impact Assessment Checklist or Risk Assessment Report: An impact assessment checklist or risk assessment report is used to document the evaluation of potential risks and effects of the proposed change on product quality, processes, systems, or regulatory compliance. If the assessment is not incorporated directly within the change request form, it should be maintained as a separate, controlled document.
• Implementation Plan and Task List: The implementation plan and task list outline specific actions, responsibilities, and timelines for executing the approved change. The implementation plan and task list can be part of the change request form or can be maintained as a separate, controlled document linked to the change request to maintain traceability.
• Evidence of Executed Tasks: The evidence of executed tasks includes supporting documentation such as validation protocols and reports, training records, or audit reports that confirm task completion.
• Effectiveness Check Report or Form: The effectiveness check report or form documents verification that the change achieved its intended objectives without unintended negative impacts.
• Change Control Log: Change control log is a centralized register that tracks all change control activities and their status. A change control log is needed when the process is managed manually.

What Are the Regulatory Requirements for Pharma Change Control?

Regulatory requirements for change control in the pharmaceutical industry define the mandatory expectations established by authorities to ensure that any change potentially affecting product or critical processes is properly assessed and documented.

The key regulatory frameworks specifying change control requirements for the pharmaceutical industry are the following.

• EudraLex Volume 4: EudraLex Volume 4, or EU GMP, requires that all changes must be prospectively evaluated, approved before implementation, and verified post-implementation to confirm that quality objectives were achieved without negative impact on product quality.
• FDA 21 CFR Part 211: Part 211 mandates procedures and controls to prevent unauthorized changes and requires documentation of modifications to manufacturing, processing, packaging, and laboratory controls.
• ICH Q10: ICH Q10 for pharmaceutical quality system emphasizes the need for an effective change management system integrated into the pharmaceutical quality system to evaluate, approve, and implement changes while managing risks and ensuring continual improvement.
• ICH Q7: ICH Q7, GMP guide for Active Pharmaceutical Ingredients (APIs), specifies that written procedures must control changes in materials, methods, and equipment, requiring formal review and approval by quality units to prevent unintended effects on API quality.
• WHO GMP: WHO GMP in Annex 2 of TRS 986 requires that changes should be evaluated and approved before implementation, with post-implementation review confirming that the changes met their objectives and did not affect product quality.
• PIC/S GMP: PIC/S GMP Part I aligns closely with EU GMP and Part II with ICH Q7, reinforcing the need for prospective evaluation, approval, and documentation of all GMP-relevant changes across pharmaceutical manufacturing operations.

ISO 9001:2015 for quality management systems requires organizations to maintain documented control over changes to processes and systems, ensuring that modifications are reviewed, approved, and implemented under controlled conditions.

EudraLex Volume 4

EudraLex Volume 4 is a set of European Union guidelines interpreting the principles of GMP for medicinal products intended for both human and veterinary use. EU GMP’s main purpose is to ensure that medicinal products are consistently produced, controlled, and distributed according to quality standards that safeguard patient safety.

The scope and applicability of EudraLex Volume 4 is across all EU member states and applies to manufacturers and importers of human and veterinary medicinal products. EU GMP covers all stages of production and control, including those related to starting materials. Part II of the guideline applies to Active Pharmaceutical Ingredients (APIs) used as starting materials, ensuring their manufacture and control align with GMP principles.

EudraLex Volume 4 addresses change control and change management throughout several chapters. In Chapter 1 (Pharmaceutical Quality System), clause 1.4 (xii) requires arrangements for the prospective evaluation and approval of planned changes before implementation, including regulatory notifications when applicable. Clause 1.4 (xiii) mandates that after implementation, an evaluation must confirm that quality objectives were achieved and that no unintended deleterious impact occurred on product quality. In Chapter 4 (Documentation), clause 4.29 requires the establishment of written procedures for change control.

Chapter 5 (Production) in clause 5.25 requires validation for any significant amendments to manufacturing processes, equipment, or materials that could affect product quality or process reproducibility. In Chapter 6 (Quality Control), clause 6.33 notes that ongoing stability studies should include batches manufactured after significant changes or deviations to confirm continued product stability and quality.

Part II, paragraph 13 specifies the requirements for change control related to API manufacturing, reinforcing that changes impacting raw materials, equipment, processes, or systems must be properly reviewed, documented, and approved before implementation, and their effectiveness should be reviewed post-implementation.

FDA 21 CFR Part 211

FDA 21 CFR Part 211 establishes the GMP requirements of the U.S. Food and Drug Administration for the manufacturing, processing, packing, or holding of finished pharmaceutical products intended for human or animal use. Part 211 provides the regulatory framework to ensure that drugs are consistently produced and controlled according to quality principles that guarantee their safety, quality, and purity.

All pharmaceutical manufacturers supplying the U.S. market, including both domestic and foreign facilities, are under the scope and applicability of FDA 21 CFR Part 211.

Change control and change management are referred to in several sections of FDA 21 CFR Part 211. Clause 211.68 requires that computer and related systems have appropriate controls in place to ensure that changes in master production and control records or other records are made only by authorized personnel.

Clause 211.100 mandates the establishment of written procedures for production and process control to ensure product consistency and quality. These written procedures, including any changes, must be drafted, reviewed, and approved by appropriate organizational units.

Clause 211.160 addresses laboratory control, specifying that the creation or modification of specifications, standards, sampling plans, or test procedures must be drafted by the relevant department and approved by the quality control unit.

Together, these requirements form the foundation of change control under FDA cGMP, ensuring that all changes affecting manufacturing, documentation, or testing are properly controlled, authorized, and traceable.

ICH Q10

ICH Q10 is an international guideline developed by the International Council for Harmonization (ICH) that establishes a model for an effective pharmaceutical quality system. ICH Q10 supports the integration of quality management principles throughout the product lifecycle, fostering a robust quality culture within pharmaceutical organizations.

The scope and applicability of ICH Q10 extend globally across the pharmaceutical industry. Although it is not legally binding, regulatory authorities such as the FDA, EMA, and other national authorities recognize it as a foundational framework for quality management systems.

ICH Q10 identifies change management as one of the four key elements of a pharmaceutical quality system, alongside process performance and product quality monitoring, corrective and preventive actions, and management review.

Section 3.2.3 of ICH Q10 refers to the change management system, stating that quality risk management should be used to evaluate proposed changes, and the level of formality should correspond to the level of risk. ICH Q10 introduces a lifecycle approach to change control, requiring that all changes be properly evaluated, approved, and verified for their effectiveness to ensure continued product quality, safety, and compliance at every stage of a product’s lifecycle.

ICH Q7

ICH Q7 is an international guideline that establishes GMP requirements for the manufacture, control, and distribution of Active Pharmaceutical Ingredients (APIs). ICH Q7 provides a structured framework for maintaining control over API manufacturing operations, ensuring consistency, traceability, and compliance with regulatory expectations.

ICH Q7 applies globally to API manufacturers supplying pharmaceutical markets. ICH Q7 is not legally binding. However, ICH Q7 is widely adopted and serves as a primary reference during audits of API manufacturers.

ICH Q7 addresses change management in Chapter 13, under the title change control. Clause 13.11 specifies that written procedures must be in place to identify, document, review, and approve all GMP-relevant changes to materials, equipment, analytical methods, facilities, support systems, and computer software.

ICH Q7 requires that proposed changes be evaluated for their potential impact on product quality and regulatory compliance, and suggests classification systems (e.g., minor, major). ICH Q7 emphasizes the use of scientific judgment in determining what additional testing and validation studies are appropriate to justify a change in a validated process.

WHO GMP

WHO GMP refers to the GMP guidelines established by the World Health Organization (WHO) to ensure that pharmaceutical products are consistently manufactured with appropriate quality and safety. WHO GMP guidelines provide a global framework for manufacturing operations, emphasizing product quality, process control, personnel hygiene, documentation, and validation.

The scope and applicability of WHO GMP are global, supporting pharmaceutical manufacturers, regulatory authorities, and procurement agencies. WHO GMP is used as the basis for national GMP regulations in many countries. However, the WHO GMP is not legally binding. WHO GMP applies to all stages of pharmaceutical manufacturing, from raw material handling to final product release and distribution.

WHO GMP includes requirements for change control in Technical Report Series (TRS) No. 986, Annex 2, specifically in Chapter 1: Pharmaceutical Quality System. WHO GMP, similar to EU GMP, requires arrangements to be in place for the prospective evaluation and approval of planned changes before implementation, taking into account any necessary regulatory notifications or approvals. WHO GMP further mandates that after a change is implemented, an evaluation must confirm that the quality objectives were achieved and that no unintended adverse effects occurred on product quality.

PIC/S GMP Guide

PIC/S GMP refers to the GMP Guide developed by the Pharmaceutical Inspection Co-operation Scheme (PIC/S), an international organization composed of regulatory authorities working together to harmonize GMP standards and inspection procedures. PIC/S GMP guide establishes a unified framework for the manufacture and quality control of medicinal products for human and veterinary use, promoting consistent GMP enforcement and confidence among regulatory agencies worldwide.

PIC/S GMP Guide applies across member countries, which include regulatory authorities from Europe, the United States, South America, Asia, and other regions. Although not legally binding, the PIC/S GMP is an inspection reference guide for member authorities and supports mutual recognition agreements (MRAs), reducing duplication of regulatory inspections and improving global GMP compliance consistency.

The PIC/S GMP Guide has requirements for change management in both Part I (for finished medicinal products) and Part II (for active pharmaceutical ingredients). Both sections mirror the requirements of the EU GMP guidelines, including the need for prospective evaluation, approval, and documentation of planned changes and post-implementation evaluation to confirm that quality objectives were achieved without adverse effects. Part II, similar to ICH Q7, outlines detailed requirements for managing changes in API manufacturing.

What Are the Best Practices in the Pharmaceutical Change Control Management?

The best practices for change control management that a pharmaceutical company should adopt are listed below.

• Have a Well-Defined, Documented Process: Establish a standardized procedure that clearly outlines the steps, responsibilities, and approval flow for managing all GMP-relevant changes to ensure control and consistency.
• Keep Complete and Clear Change Documentation: Maintain comprehensive records of each change, including justification, risk assessment, approvals, and supporting evidence, to support traceability of actions.
• Conduct Comprehensive Risk Assessments: Evaluate the potential impact of proposed changes on product quality, safety, and compliance using quality risk management tools.
• Involve Cross-Functional SMEs: Engage subject matter experts from all impacted departments, such as quality assurance, production, engineering, and regulatory affairs, to ensure informed decision-making.
• Monitor Change Action Items: Track progress of all assigned tasks to ensure timely completion and resolution of any issues that arise during implementation.
• Integrate with Other Quality Systems: Manage change control as an integral part of the company’s QMS. Interrelate systems such as CAPA, deviation management, training, and validation to maintain oversight during change implementation.
• Leverage Technology: Use an electronic quality management system to streamline workflows, manage reviews and approvals, and ensure real-time visibility of change control activities.
• Establish Change Control Metrics: Define measurable indicators such as change control closure time, overdue tasks, and change control effectiveness rate, to assess process performance and drive continual improvement.

What is the Role of Pharmaceutical QMS Software in Streamlining Change Control Management?

A QMS software in the pharmaceutical industry is a digital platform designed to manage quality processes in compliance with GMP and other regulatory standards. The primary purpose of QMS software in the pharmaceutical industry is to ensure consistent control, traceability, and efficiency across quality operations such as document management, CAPA, training, and change control.

A QMS software streamlines the change control management in the following manner.

• Centralizes and Standardizes the Process: An eQMS consolidates all change control activities in one system, ensuring not only consistency but also easy access to SOPs and change control data across departments.
• Automates Notifications: A QMS software can send alerts and reminders for approvals, pending actions, and due dates, ensuring timely follow-up and accountability.
• Provides Visibility and Tracking: An electronic QMS enables monitoring of change status, progress, and metrics, improving transparency and control.
• Integrates with Other Quality Processes: Within an eQMS, change control is connected with CAPA, training, and document control systems, maintaining end-to-end traceability of actions and event sequence.

The key features of QMS software relevant to change control management in the pharmaceutical industry are given below.

• Standardized Workflows: An eQMS ensures all changes follow predefined approval and review steps.
• Built-in Templates: A QMS software may provide ready-to-use, compliant forms and templates for initiating change requests.
• Electronic Signatures: An eQMS software must comply with FDA 21 CFR Part 11 and EU Annex 11 requirements, ensuring secure and legally binding electronic approvals.
• Document Control Integration: Within an eQMS, related documents, such as SOPs or validation protocols, can be linked directly to change records for improved traceability.

The main benefits of QMS software implementation for pharmaceutical change control systems are the following.

• Increased Efficiency: An eQMS automates manual or repetitive tasks, such as reminders, reducing administrative burden and shortening change cycle times.
• Enhanced Compliance and Audit Readiness: Within an eQMS, complete records and approval histories are maintained, enhancing audit readiness.
• Improved Data Integrity: Ensures controlled, accurate, and tamper-proof change control record management.

SimplerQMS helps pharmaceutical companies streamline and strengthen change control management through its fully validated, cloud-based platform. SimplerQMS offers integrated modules that standardize workflows, maintain compliance, and ensure complete traceability across all change-related activities.

The following modules of SimplerQMS support the pharmaceutical companies in the change management process.

• Change Management Module: The change management module in SimplerQMS enables full lifecycle change control tracking, from initiation to post-implementation verification. Integrated approval workflows, electronic signatures, and automatic notifications streamline compliance with GMP requirements.
• Risk Management Module: The risk management module supports change impact assessments and integrates seamlessly with the change control process. Risk management module aligns with ICH Q10 guidelines to identify, evaluate, and mitigate risks associated with proposed changes.
• CAPA Management Module: The CAPA management module connects corrective and preventive actions to change records, providing a closed-loop quality system, strengthening audit readiness, and supporting continuous improvement.
• Deviation Management Module: The deviation management module allows deviations to be linked to changes, ensuring transparent documentation.
• Training Management Module: The training management module links training assignments to changes. Through the training management module, a company can ensure that affected personnel are up-to-date on SOP revisions tied to change implementations.
• Document Control Module: The document control module maintains version-controlled records of all documents affected by changes.
• Quality KPIs Module: The quality KPIs module supports companies in monitoring metrics such as change effectiveness rates and overdue tasks. Key performance indicators help drive data-driven decisions and continuous improvement in change control management.