Pharmaceutical Validation Validation Practices for the Pharmaceutical Industry

Author / Editor: Deepak Makhijani, Consultant / Dominik Stephan

FDA regulatory compliance is a mission-critical requirement. If the FDA finds a manufacturer to be non-compliant to or in violation of FDA rules, the consequences can be severe with warning letters, mandatory product recalls, temporary shut-downs, criminal penalties and fines depending on the severity of the violation. These penalties imposed could seriously dent the manufacturer’s brand image, and at times could even cripple the manufacturer financially.

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Personnel maintaining and documenting modifications that have been carried out since the previous shift cycle at a pharmaceutical factory
Personnel maintaining and documenting modifications that have been carried out since the previous shift cycle at a pharmaceutical factory
(Picture: / Alexander Raths)

If a manufacturing process is highly automated, the basic process control system will play an important role in obtaining quality certification for the process. Every organization that utilizes such systems has a support structure of personnel and procedures to maintain and modify these systems; albeit in many cases this infrastructure may be lacking in documentation, producing a system which can be insecure and vulnerable for a process seeking quality certification.

Whether trying to achieve certification or improve the integrity and security of this vital piece of operating equipment, one should take this opportunity to develop a methodology that not only documents the system’s logic, but documents the personnel and procedures that support the system, as well. Accurate documentation can prove to be extremely valuable to the reliability of the process unit and worth the effort to maintain.

Need for Regulatory Compliance

This documentation process provides guidance to persons who are subject to ‘Part 11’. This arises from the necessity of fulfilling a statute or another part of the FDA’s regulations to maintain records or submit designated information electronically. On a wider scale, Part 11 applies to records in electronic form that are created, modified, maintained, archived, retrieved, or transmitted under any records requirements set forth in agency regulations.

Part 11 also applies to electronic records submitted to the agency under the Federal Food, Drug and Cosmetic Act and Public Health Act (PHS Act), even if such records are not specifically identified in agency regulations.

The underlying requirements set forth in the Act, PHS Act and FDA regulations (other than part 11) are predicate rules given as follows:

  • A common enterprise wide IT system to provide visibility into the processes and performance metrics at various operational and management levels
  • That an enterprise solution should also be immutably linked to all components of manufacturing (including equipment, raw materials and inventories) analytical laboratories as well for the distribution— purview of USFDA for capturing nonconformance out of spec production, tracking and managing the corrective action process
  • IT system to have audit trail for ensuring successful implementation of recommendations
  • IT system should also improve efficiency and speed in operations as well as regulatory processes.

General Approach to Compliance

The FDA suggests that the decision to validate computerized systems, and the extent of the validation, take into account the impact the systems have on the company’s ability to meet predicate rule requirements.