By Erin Hoffman, Lead Validation Engineer


In the pharmaceutical industry, the change control process serves an important role. Although the cGMP regulation for drug products (21 CFR 211) has no direct reference to change control, it is implied in 211.100(a) and 211.160(a). It is required that changes in production procedures and process controls be reviewed and approved by the appropriate organization units and quality control unit. A change management system is required for managing, evaluating, implementing and documenting changes. The objective of the process is to prevent unintended consequences that could impact quality. Changes are the result of initiatives aimed at improving quality, increasing yield, reducing costs, cutting waste, and streamlining processes. The change management process should be utilized for changes to equipment, location, process control parameters, batch size, shelf life, storage conditions, facility layout, raw material sources, hardware or software, standard operating procedures, cleaning agents, and so on. One of the most important aspects of the change control process is to maintain a history of changes for audit trail purposes.

Any modification to the control strategy or manufacturing method of a product introduces some risk of causing adverse impact. When considering a change, the benefit of the proposed change must outweigh the risk of causing adverse impact to the product/patient. When changes are proposed and implemented the potential quality impact must be evaluated. The need for additional testing, revalidation, or requalification must be carefully analyzed to ensure a validated/qualified state is maintained. Changes to an established process must be controlled and documented.

A change proposal must include the following:

  • A unique traceable change identifier.
  • A detailed description of the objective of the change.
  • The justification for the proposed change.
  • Assurance that the change will not impact product quality.
  • A thorough analysis of the impact of the change.
  • An implementation plan that includes the actions and timing.

The level of detail in the change proposal should correspond with the complexity of the change.

The proposed change, based on its scope and criticality, may have an impact on the product, material, or API, the control strategy that ensures product quality and consistency, or the state of validation or qualification. An evaluation of the change on the following critical attributes related to the product or API should be conducted:

  • Safety
  • Identity
  • Strength
  • Purity
  • Quality
  • Expiration dating period
  • Stability

The impact that the change may have on the validation or qualification state of the following may be required, including the need to revalidate or requalify:

  • Process
  • Equipment, facilities, and utilities
  • Computer systems
  • Analytical test methods
  • Medical devices

Change proposals that may potentially impact reporting requirements must be communicated to regulatory affairs for evaluation. All changes must be implemented according to the approved implementation plan. The implemented change should be evaluated for effectiveness.

The major benefit of a change control implementation is that it facilitates compliance in a regulated environment while supporting change for continuous improvement. Change control ensures that a company continues to comply with GMP requirements. For more information on change management, visit our page on FDA change management or contact our team for a free consultation.

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