Change Control and Management

Change Control and Management in Pharmaceuticals 

The United States Food and Drug Administration (FDA) provides very specific requirements for change control and management, requiring written procedures for production and process controls to ensure that drug products have the identity, strength, quality, safety, and purity they purport or are represented to possess, and that medical devices are safe and effective. These requirements extend beyond procedures and work instructions to include changes to specifications, products, labels, methods of testing and production, packaging, equipment, and facilities.

21 CFR 211 and 820 provide the requirements for establishing and maintaining documents, including requirements for reviewing, for adequacy, and approval before issuance. The quality unit (QU) is ultimately responsible for the change control and management function. However, other functions usually participate in the process depending on the application and requirements, including engineering, production, manufacturing, distribution, regulatory affairs, and clinical.

Procedures for production and process controls are usually birthed or modified using a predetermined engineering change control (ECO) system. The ECO system usually includes a list of requirements and considerations, an evaluation checklist, and required signatures. The complexity of the change usually determines the level of control and authorization required. For example, to update a procedure that contains a grammatical error may be considered an administrative change and therefore allow for an abbreviated approval and signature process, whereas a procedural change that modifies a critical process parameter usually requires the full evaluation and approval process, including risk analysis and change effectiveness. Figure 12.1 depicts a typical change control process.

Changes to procedures for production and process controls include a description of the change, identification of the affected documents, the signature of the approving individual(s), the approval date, and when the change becomes effective. Obsolete documents are promptly removed from all points of use. This process is necessary to prevent unintended use of obsolete documents. 

Written production and process control procedures are followed in the execution of the various production and process control functions, and are documented at the time of performance. Any deviation from the written procedures must be recorded and justified. Deviation should be reviewed by the quality unit to ensure no deleterious effect and that the drug products have the identity, strength, quality, safety, and purity they purport or are represented to possess. When deviations occur, it may necessitate the use of the nonconformance (NCR) and/or the out-of-specification (OOS) process as appropriate. Another consideration when production and process control functions are birthed or changed is notification and training. It is required that approved changes be communicated to the appropriate personnel in a timely manner, and, where appropriate, the personnel are trained on the changes.