Life-cycle approach to quality systems
The application of the process validation life-cycle approach to pharmaceutical quality systems and compliance is proposed.
Application of the life-cycle approach causes a comprehensive and continuing approach to quality systems. Quality systems
must be properly designed to accomplish system objectives. After satisfactory establishment and ongoing operation of the system,
performance should be appropriately monitored and evaluated. Corrections and improvements should be initiated as indicated.
Execution and compliance in quality systems must not be static and should be continually improved.
Table I: Compliance master plan strategy and approach.
Compliance master plans
It is proposed that documentation of the CbD program be contained in a compliance master plan (CMP). The CMP is analogous
to the current and well-accepted VMP. The concept of a CMP has been suggested by Nash (6) based on the work of Borkar (7).
These authors proposed that six quality systems and 26 quality-system elements form the basis for a CMP. Table I provides
an example CMP table of contents indicating section titles according to a quality-systems structure (8). Table II describes
the specific content of a chapter discussing a quality system using the CbD general concept.
Table II: Compliance by design and compliance master plan quality system chapter content.
Why implement CbD and CMP?
The following are potential benefits to implementing the CbD and CMP approach to quality systems and compliance:
- Organized and comprehensive focus on quality systems and compliance: Objectives, key attributes, successful performance, and
improvement commitments should be clearly defined.
- Cross-functional thinking: The CbD approach to quality systems should break down organizational barriers and ensure consistent
compliance objectives, attributes, risk assessments, and so forth, between functional areas.
- Consistent prioritized mitigation activities across functions: CbD should potentially facilitate consistent focus on high-risk
activities and mitigation of high-risk problems.
- Proactive variation identification and control strategy: CbD requires prospective consideration of potential input variation
and development of a control strategy to minimize potential compliance issues.
- Standardized audit expectations and documentation: Maintaining the CMP, including project commitment dates, keeps the organization
in a continuing state of readiness for regulatory and other audits.
- Centralized tracking of commitments: The CMP document centralizes all commitments and should serve as the primary resource
for tracking information in the same manner as the VMP.
- Organization commitment, transparency, and credibility: Implementing a CbD and CMP approach should facilitate organizational
transparency regarding compliance, foster accountability, and increase the credibility of the compliance effort with auditors
and with employees who do the work of compliance.
Implementation strategy and approach
The CbD-approach proposal may be implemented by building on current quality-systems programs and VMP content that already
exists at the manufacturing site. FDA has been auditing according to the quality systems approach for several years. Industry
may already have functional structures and documents organized according to quality systems such as validation and the VMP.
Identification of major quality systems.
Using the six FDA quality systems as a starting point, all the distinct quality systems in the organization should be specified.
For example, validation, product stability, and annual product-review programs are currently listed under the FDA Quality
System. These may be separated as individual quality systems for administration by the CbD approach. Programs that support
multiple quality systems might also be specifically separated. For example, training is mentioned in all FDA quality systems.
A separate training quality system could be specified under the CbD approach.