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
Fermentation process development begins with strain selection and optimization, media development, process development, and
scale-up to maximize productivity. Downstream processing can use various technologies for extracting, concentrating, and purifying
the product from a dilute fermentation broth. Any provider of custom fermentation services must be proficient in these aspects.
Figure 2 (ALL IMAGES ARE COURTESY OF PFIZER INC.)
Flexibility in the types of microbial systems with which a contract manufacturer can work is important because it ensures
a broad base of staff knowledge and expertise across a wider spectrum of microorganisms. When looking through product literature
or otherwise evaluating contract capabilities, the following capabilities are typical: microbial cells (bacterial and fungal),
microbial enzymes, recombinant organisms, enzymatic bioconversions, and secondary metabolites.
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
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