- facility- and equipment-design review to ensure compliance with CGMP regulations;
- project scope definition, organization, and planning;
- project labor requirements and budget;
- validation master plan development.
Part 2 will continue with a discussion of the following validation-related subjects:
- protocol and SOP development, scheduling, and implementation;
- design- and construction-document collection (turnover package);
- evaluation of deviations and discrepancies.
In general, process equipment and utility systems affecting product quality or contacting product are the subject of design review. Typical reviewed utilities include heating, ventilation, and air-conditioning (HVAC), compendial waters (e.g., water-for-injection, purified water, clean steam), and compressed gases such as nitrogen and compressed air. At present, regulatory expectations for other utilities such as chilled water or plant steam are minimal, and these may be omitted. Design review is mandatory for highly customized or unique process equipment, particularly when the unit is custom manufactured. Equipment for critical processes such as aseptic filling and packaging, lyophilization, and final purification also requires rigorous evaluation. Because the GMP regulations are interpretive and nonspecific for equipment design and construction, the design engineer and owner are responsible for assessing compliance (1).During the design review stage, the engineer and owner should evaluate all critical specifications and drawings to ensure that regulatory compliance is achieved. In general, experienced vendors understand the requirements imposed by GMP regulations and design and construct their equipment and systems accordingly. Rarely are serious design and construction errors uncovered because a reputable vendor's knowledge and understanding of GMP-compliant design often exceeds that of the owner and engineer combined (2). Design reviews should be performed using a structured and systematic approach. For mechanical systems such as HVAC, the evaluation of drawing sets takes precedence over most other documents. Vendor submittals always should be reviewed. Although less beneficial, Division 15, 22, and 23 type construction specifications (3) also should be examined, even though these are often standard with little customization. Checklists and other reviewing aids may be valuable because they prove that the designs were evaluated and they may be used again for subsequent projects.
Three critical steps must be taken in a design review:
- identify and evaluate any potential areas or items of noncompliance;
- ensure that designs are modified to eliminate noncompliant features;
- prepare a brief report that summarizes the design-review process and obtain appropriate approvals, including quality assurance.
Much of the current content in both domestic and foreign GMP regulations is limited and nonspecific. The owner is obligated to review all designs and verify conformance with industry standards and regulatory guidelines. In the absence of standard equipment specifications within the GMPs, logic dictates that process equipment and utilities must be designed to be: