Fermentation process experience

Although it sounds like an obvious factor, GMP fermentation experience is extremely important but easy to overlook. Several factors should be taken into consideration to determine whether a prospective supplier is equipped to handle fermentation services.

Figure 2 (ALL IMAGES ARE COURTESY OF PFIZER INC.)

A company should also rate a prospective partner on fermentation downstream processing. A well-rounded capabilities portfolio includes various technologies for extraction and purification. A fermentation services provider should be able to easily handle soluble and insoluble products in the fermentation broth using technologies such as centrifugation, ion exchange, large-scale distillation, nanofiltration, large-scale crystallization, filtration, and drying.

Process development and ongoing production support are additional tools a contractor should have at its customers' disposal. Troubleshooting and process optimization (to reduce costs and improve processes) are two important examples. Operating a biological process such as fermentation is a great deal more complex than operating a chemical synthesis process, largely because there are many more variables to consider and control. For example, the media components used in fermentation are essentially agricultural products like soy, corn flour, natural cereals, fats, and oils, and other materials that can literally vary from crop to crop, harvest to harvest, and year to year. The fermentation services contract manufacturer must manage these natural changes on a day-to-day basis, taking them fully in stride and adjusting its process accordingly.

Beyond initial outlays for any specialized equipment required, a contractor should sustain an aggressive maintenance program that includes annual or periodic calibrations of sensitive instruments. When evaluating a provider, ask to see its maintenance schedule or other proof that equipment is adequately cared for and updated as required.

The team running all this technology is equally as important. Initial and ongoing training in all aspects of fermentation is essential and includes operator, laboratory analyst, and specialized support-staff training. All personnel should have required curricula for their fermentation-related assignments. Training is not limited to providers of fermentation services, it is an integral part of GMP, and the complexity of fermentation processes underscores its importance when potential partners are evaluated.

Another important contract manufacturing criterion, and is by no means restricted to fermentation services, is technical development and regulatory support. A potential provider should understand its customer's drug products, markets, and business needs. Ideally, the provider will maintain an experienced team of professionals that provides a continuous surveillance of global regulatory and CGMP requirements, and writes and maintains worldwide registration documents. Typically, such a customer support team will handle the technical package, quality agreements, customer audits and inquiries, technical facilitation, investigation support and supply team feedback, among other responsibilities. If the fermentation provider can't point to a standing team capable of helping manage these details, think twice before engaging with them. Fermentation operations are complex and can easily consume the customer's time if a contractor isn't willing or able to offer such a range of technical and regulatory value-added services.