Essentials of Validation Project Management Part 2

Reliable and controlled. Control systems such as programmable logic controllers (PLCs) should be used to control equipment. Automation allows processes to be replicated without variability, a fundamental principle on which GMPs are based. Mechanical-type (cam) controllers should be avoided because regulations require that current and modern technology be used. Manual control also should be avoided where possible because replication is inherently difficult. Any system that may alter batch-to-batch uniformity, and ultimately the product therapeutic response, must be very carefully considered.
Correct for application. The correct design criteria must be specified. For example, clean compressed air must have a dewpoint temperature of approximately –40 °F to prevent condensation. Refrigerated air driers cannot meet this requirement. Oil-free compressors should be used to exclude oil contamination unless several levels of filtration are used (4). Industry standards allow no more than 1 ppm (1 mg/m³ ) of oil/hydrocarbon in compressed air.
Besides developing some original standards for process equipment design and construction, the pharmaceutical industry has borrowed standards from industries that produce similar consumer products, most notably the dairy industry. The 3-A Sanitary Standards are voluntary guidelines followed by dairy equipment vendors and dairy operators. The standards provide material specifications, design criteria, and other necessary information for the construction of dairy equipment to satisfy public health concerns. The ultimate objective is to safeguard public health from contaminated dairy products.
To meet this objective, 3-A Sanitary Standards and 3-A Accepted Practices ensure that dairy, food, and other microbial-sensitive products are protected from contamination; that all product contact surfaces can be cleaned in place or easily dismantled for manual cleaning; and that all product contact surfaces can be easily inspected to confirm cleaning effectiveness (5). The purpose of these standards and their application to pharmaceutical manufacturing are readily apparent. The 3A Sanitary Standards should be consulted when equipment such as holding tanks, clean-in-place systems, valves, and pumps are undergoing GMP compliance review. Design errors are uncommon, however, because most equipment vendors already fully understand and comply with these standards. For high-value projects and facilities intended to manufacture sterile products, it is often required and worthwhile to contact the local FDA district office. This alerts the agency that inspections must be scheduled, often to coincide with critical construction milestones and events. FDA Office of Regulatory Affairs Field Management Directive (FMD) 135 also encourages manufacturers to contact FDA when facility and equipment designs are being prepared (6). The following is a summary of FMD 135, which can be found on FDA's Web site:
Providing [FDA] review and comment is desirable because it may reveal [design] defects early and prevent costly construction errors which could lead to defective operations and products. It also affords FDA the opportunity to become aware of future work load obligations and, in some cases, new technologies. Early field involvement with new or modified facilities will increase efficiency and result in the timely processing of applications (6).
Companies should understand and recognize that partnering with FDA to review proposed designs is beneficial to both parties. Costs and delays associated with rework can be avoided if problems are detected early. Definitive dates for facility inspections can be established, which serve as endpoints that motivate project completion. Current agency inspectional focus also may be apparent, foretold by the types of questions that are asked. Overall, early dialogue and FDA involvement may expedite facility completion, reduce engineering and construction costs, and lead to a smooth transition from start-up to operation. These results are desirable for all manufacturers, regardless of company size or complexity.
Scope definition, organization, and planning
Successfully implemented validation projects all begin with a well-defined scope (i.e., the set of activities and deliverables that must occur to complete the project). Scope definition is critical if contracted validation resources are used because it becomes the basis for cost estimates and assessing job completion.