Essentials of Validation Project Management Part 3

These four types of documents are common and essential to all validation projects, although the level of detail and content may vary. Design-document quality is usually closely associated with cost; the greater the upfront engineering costs, the more detail that can be found in drawings and lists. Because facility construction and protocol preparation require drawings that are detailed, accurate, and thoroughly checked, increased funding for engineering services is usually money well spent. In general, one can expect that the cost of facility-design services will be approximately 10–12% of the facility's total installed cost.
It is useful to identify project activities on a spreadsheet when establishing project scope. Systems and equipment requiring qualification and validation are first determined by reviewing the project documents described previously. Then, the spreadsheet is created and the first column is reserved for each identified system and piece of equipment. Adjacent columns become a matrix of activities necessary to complete system and equipment qualification. Column headings and subheadings usually consist of the following:
  • document collection and review (to develop protocols and SOPs);
  • calibration and metrology;
  • protocol preparation (installation qualification [IQ], operational qualification [OQ], performance qualification [PQ], and cleaning);
  • protocol execution (IQ, OQ, PQ, and cleaning);
  • final reports;
  • turnover packages (contain construction test reports, as-built drawings);
  • SOPs (operation, maintenance, cleaning).


Table I: Estimated labor hours for commissioning and qualification.
A checkmark is placed in each cell for which a specific activity is required. This checkmark may be replaced eventually with the name of the individual responsible for the activity. Assigning labor hours to each checkmark is even more useful because this provides an estimate of the labor required for each activity and for the entire project . Project labor requirements and budgeting By revising the spreadsheet to include labor hours, and then totaling each row and column, a project labor estimate per activity and system can be derived (7). Dividing total project hours by 2080 h/year provides an estimate of personnel required to complete all activities. Total project headcount will vary depending on project duration, however. Anticipating the number of labor hours is important because the labor involved may exceed available resources, thus requiring that outside validation services be contracted. Assigning a dollar amount (e.g., $75) to each hour of labor provides an estimate of validation project costs, which often is used to justify requests for financial resources and to support the annual budgeting process.
Industry experience has shown that validation costs (excluding commissioning and process validation) typically range from 2.5–5% of the total installed cost of the facility. Aseptic-filling and biotechnology facilities frequently have the highest validation cost, whereas API facilities tend to be the least expensive. Care must be taken not to apply these guidelines too tightly because the percentage validation cost will vary with project size. As an example, the purchase and installation of a small steam sterilizer might have a total installed cost of $150,000; however, the validation costs may exceed $50,000 (33%), when protocol preparation and implementation, SOP development, and laboratory supplies are considered. 
The facility revalidation program also should be described in the master plan because the validation life cycle continues long after the facility is mechanically complete and handed over for operation. Revalidation usually takes two forms: time or event based (9). Time-based revalidation is the practice in which a system or process is recertified at a specified interval. Time-based assessments also can include a review of historical system performance data. Event-based revalidation is implemented whenever physical or operational changes are made to the system outside the scope of the original validation. All such modifications are the subject of the facility's change control program, which also should be described in detail in the master plan.
Turnover package (TOP) development also can be described in the master plan. Turnover package is a system for organizing all documents related to facility and system design, construction, and start-up relevant to the eventual commissioning and qualification of systems and equipment (10). Turnover packages are usually prepared by the construction manager and turned over to the owner at project completion. TOP documents construction activities and contributes to system IQ, OQ, and PQ and usually is a prospective or concurrent activity (i.e., design, construction and start-up documents are compiled as system construction proceeds). Turnover packages will be discussed in detail in Part 2 of this article.
Summary
This article provides a basic introduction to four components that are fundamental to all successful validation projects. Part 2 will describe three additional programs that should be considered and implemented. Before undertaking any validation project, careful planning to arrive at a logical, uncomplicated approach is required. All projects are labor and capital intensive, and incorrect or inefficient use of either resource ultimately escalates cost and extends the schedule. All validation projects must begin with a comprehensive design review and include FDA assistance if necessary. Once a compliant design is finalized, validation project scope must be established and properly communicated to all project stakeholders. Concurrent with project-scope definition is the development of a labor estimate, and by extension, a cost estimate. Knowing labor requirements and costs early helps identify potential shortfalls in personnel and permits appropriation of sufficient funding to complete the project. Accurately defining project scope also avoids misunderstandings, errors, and omissions when work is assigned to contractors and company personnel. A comprehensive validation master plan follows design review and scope definition in the project timeline. The master plan identifies critical project activities, communicates expectations, and conveys a quality mindset and state of control to regulators. Each of these project components, in conjunction with the guidelines and programs described in Part 2 that follows, helps assure that the project is completed on time and within budget. More importantly, quality is built into the project from the start, regulatory compliance is realized, and the transition from start-up to operation is optimized. In the current environment of cost control, expedited product introductions, and increased regulatory oversight, the benefits of efficient validation project management should be evident.
William Garvey is a senior advisor at Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, tel. 860.715. 2277, fax 860.715.7806,
References
1. US Food and Drug Administration, Code of Federal Regulations, Title 21 (FDA, Washington, DC, April 1, 2005), pp. 120–141.
2. W. Garvey, "Integrated Validation Programs for Solid Dosage Facilities—Part 1," Am. Pharm. Rev. 2 (2), 33–39 (1999).
3. The Construction Specifications Institute (Alexandria, VA).
4. Department of Health, Education and Welfare, "Human Drugs—Current Good Manufacturing Practice in Manufacture, Processing, Packing or Holding of Large Volume Parenterals, and Request for Comments Regarding Small Volume Parenterals," Fed. Regist. 41 (106), 22022–22115 (June 1, 1976).
5. 3-A Sanitary Standards Inc., McClean, VA.
6. FDA, "ORA Field Management Directive 135, Pre-Operational Reviews of Manufacturing Facilities" (FDA, Washington, DC, Dec. 4, 1995).
7. W. Garvey, "Effective Validation Project Management," oral presentation given at Interphex Conference 2005, New York, NY, April 26–28, 2005.
8. ISPE Baseline Pharmaceutical Engineering Guide, Pharmaceutical Engineering Guides for New and Renovated Facilities, Vol. 5, Commissioning and Qualification, (International Society for Pharmaceutical Engineering [ISPE], March 2001), pp. 11–15.
9. ISPE Baseline Pharmaceutical Engineering Guide, Pharmaceutical Engineering Guides for New and Renovated Facilities, Vol. 5, Commissioning and Qualification, (ISPE, March 2001), p. 111.
10. M. Chin, "TOP: A Rational Approach For Ensuring Proper Biopharmaceutical Plant Construction," in proceedings from PharmTech Conference '87 (Aster Publishing Corporation, Eugene, OR, 1987), p. 73.

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