Design and Construction of a Potent Pharmaceutical CGMP Suite

The author describes the approach taken to develop a facility dedicated to handling potent and cytotoxic drug substances.
Sep 01, 2009
Volume 2009 Supplement, Issue 5

This article is part of PharmTech's supplement "API Synthesis and Formulation 2009."

In 2009, Metrics opened a state-of-the-art dedicated potent and cytotoxic facility. The facility, which can accommodate Phase I through Phase III solid-oral dosage form projects up to 10 kg in size, provides containment for processes with hard-wall isolation technologies, specifically a custom-engineered system of isolators to contain solid oral dosage form processes that can be assembled to create a desired equipment train.

In developing its facility, Metrics used many design concepts from the International Society for Pharmaceutical Engineering's (ISPE's) Baseline Pharmaceutical Engineering Guide for New and Renovated Facilities, with particular emphasis on allowing for one-way flow of materials, personnel, and equipment. As the industry continues to define what is meant by "potent compound facilities," Metrics made capital investments in best-practice solutions that would offer a defensible position on the matter.

Planning and design

On the basis of its involvement with ISPE's community of practice with regard to isolation, Metrics recognized that there are several ways to address containment and many options were considered. During the project's planning phase, it was determined that although local ventilation and laminar–down-flow technologies provided some benefits, including versatility and comfort, they were heavily dependent on work practice. Spills or unanticipated discharges of powders can result in acute exposures, and although flexible containment solutions are practical and achieve good containment performance, they pose challenges from a cleaning standpoint or, if disposable, a cost of goods standpoint. Moreover, because a contract organization is likely to have a large variety of compounds moving through its facility, the management and control of these disposable "bags" can be complex.

Finally, knowing that a contract organization would be subject to scrutiny from regulatory agencies and client quality-assurance units, the company determined that hard-wall isolators designed for good manufacturing practice (GMP) applications would be the most robust and defensible containment technology. It was essential to quantify the degree of containment to substantiate any containment claim and then to develop and implement policy to ensure acceptable performance from both operator exposure and cross-contamination standpoints. The containment verification testing activities were performed in a manner that was consistent with the best industrial hygiene practices and in accordance with the guidance published in "Section II: Sampling, Measurement, Methods, and Instruments" of the Federal Occupational Safety and Health Administration (OSHA) Technical Manual and the ISPE SMEPAC Committee document, "Assessing the Particulate Containment Performance of Pharmaceutical Equipment: A Guide," (1, 2).

Merely achieving the desired technical claims would be insufficient to allow for a smooth transition from traditional personal protection equipment to isolation. The only way to frame isolation technology as something to be embraced rather than imposed was to vest employees with design responsibility. A specialized formulation development team was formed, organized under a manager reporting to the vice-president of pharmaceutical development, and charged with everything from conceptualization and design of the facilities to policy and management of its operation. The team successfully led the entire endeavor. Detailed job knowledge in the context of Metrics' overall operation was essential to a successful launch of these services.

Dedicating staff at the inception of the project provided the added benefits of limiting access to the facility, ensuring better work-practice resulting from routine experience, and instituting more centralized training in addition to the standard GMP curriculum. This team functions as a small department integrated with supporting groups from other departments such as quality assurance, employee health and safety, and analytical development.

The design effort required frequent, usually daily, meetings with architects, engineers, and other involved disciplines, including safety and equipment vendors. The formulation team (that is, the end user) had the benefit of working with a variety of talented collaborators who became increasingly comfortable with this arrangement as all parties progressed through the learning curve.

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