Manufacturing Considerations for Sourcing GMP Fermentation Services

The authors describe the critical aspects of an ideal fermentation services provider.
Sep 01, 2008
Volume 2008 Supplement, Issue 4

The need for good manufacturing practices (GMP) fermentation is likely to increase during the next several years—at a time when many pharmaceutical businesses are rationalizing and sometimes downsizing their core manufacturing operations, resulting in what many believe will be a growing need to identify outsourced fermentation sources to augment their own supply chains. Seeking additional outsourcing strategies while working to ensure quality for their end products, manufacturers are increasingly challenged when sourcing such specialized functions as large-scale fermentation.

GMP fermentation today is a complex process that requires a large investment in expertise, equipment, process, and quality control, and very few companies in the industry currently have or choose to invest in developing those resources in-house. A deep understanding of quality systems, strain development, process development, scale-up, isolation, and purification can help ensure pharmaceutical firms make the right decisions in large-scale fermentation outsourcing and help companies make the right choices for their supply-chain requirements.

Make or buy?

The fermentation of microorganisms is the basis for the production of a wide range of products such as antibiotics, hormones, and specialized proteins, thereby making fermentation an important process for related commercial products. Fermentation is frequently the preferred production method, particularly with therapeutic proteins or chemical compounds requiring a multistep synthetic process offering the optimal economic route and allowing firms to shorten their production process and time to market. Because of the importance of fermentation in the industry, it figures prominently in a company's overall decision regarding which processes and functions it must outsource.

With GMP fermentation, quality is built into the entire process, as opposed to simply testing for product quality at the end of the process. Fermentation achieved in this manner is expensive to implement—a key factor to consider. A pharmaceutical business or its fermentation services provider must maintain the facilities, procedures, and controls needed to ensure that the manufacturing, packaging, and handling of the product is conducted in a way that meets the requirements of regulatory agencies regarding safety, product identity, quality, and purity characteristics. Essentially, for a specialized function such as GMP fermentation, the "make" decision is simply not an option for most companies, and they must outsource this key process.

Fortunately, selecting an outside provider offloads a number of procedures and controls related to the fermentation process, including raw material qualification, master and batch production records, change control procedures, deviation investigations, fermentation sterilization validation, downstream process validation, cleaning validation, equipment qualification, expiration testing, and stability testing.

Perhaps the biggest factor that drives pharmaceutical manufacturers toward the "buy" decision for fermentation is cost. The capital investment for a properly equipped current good manufacturing practices (CGMP) fermentation facility, including manufacturing equipment and utilities, is significant and often runs into the high tens of millions of dollars. In addition, the provision and training of a technical staff (manufacturing, technical support, quality assurance and quality control, engineering, maintenance and utilities, etc.) further adds to the investment required. By outsourcing to a company that already has the staff and facilities in place, customers can significantly accelerate their timeline and minimize overall investment. Quite often, outsourcing to a specialized provider of custom fermentation services is the lower cost option, a key driver in swaying executive management in a time of tight cost controls.

Once the outsourcing path is chosen, the supplier selection process requires a series of key considerations for making the right contracting decisions regarding large-scale fermentation.

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