Outsourcing Versus In-House Production
Whether or not to outsource the production of a biologic is an issue that continues to generate debate, with companies having different strategies. "Having control of your own manufacturing at a certain stage, if you're a small biotech, is critical," commented Michael Buschle, Ph.D., CTO for the vaccine company Intercell (Vienna, Austria).
He suggested outsourcing at early stage, but bringing production back in-house for commercial manufacture. Intercell has reached Phase II with a classic attenuated inactivated virus vaccine for Japanese encephalitis, and this is being produced in their dedicated GMP 3,000-m2 facility in Livingston, U.K.
In contrast, a peptide vaccine, also in stage II for hepatitis C, is being outsourced as its manufacture is seen as less complex than that of a biologic. "If you want to develop products, you need to be able to manufacture them to modern regulatory requirements," Dr. Buschle added.
There may indeed be advantages to keeping manufacturing in-house, but many companies still prefer to outsource. In fact, it is estimated that almost half of all biopharmaceutical companies now contract out at least part of their manufacturing.
A major reason for the surge in outsourcing in recent years is the increased number of products in the pipeline and the growing number of new players in the business, many of whom have limited experience or manufacturing capacity.
Wynne Weston-Davis, M.D., medical and development director of Evolutec Group (Reading, U.K.), explained that outsourcing is a necessity for a virtual company such as Evolutec, which now has a third compound in Phase II. Virtuality is a business model that emerged along with the dot-com revolution in the 1990s and works for organizations that have not been able to raise much money.
Experience has shown what shouldand should notbe outsourced, said Dr. Weston-Davis. Project management at all stages needs to be kept in-house, along with target selection and development planning. But many other activities, such as documentation, can economically and safely be outsourced so long as the right contractor is chosen.
From the contractor's point of view, John MacLennan, Ph.D., business development consultant at Xoma (Berkeley, CA), which has recently set up a contract manufacturing business, explained that it was important to check that a client was realistic in their idea of time to market and general expectations, as some are more "mature" than others.
Process and technology transfer between client and contractor can be especially challenging. It is not unusual for the client to end up with a slightly modified process, and this must be supported by data.
At an early stage, processes may be poorly defined and the unexpected will often occur, as each protein and antibody is unique. "Clear, regular, and open communication is the most important issue for both contractor and client," Dr. MacLennan said.
FIT Biotech (Tampere, Finland), which is developing a DNA vaccine for HIV, uses contractors for many different activities, such as preclinical safety and toxicology, media and buffer preparation, and clinical trial monitoring, according to Tytti Krkkinen, Ph.D., vp of production.
The company's contractors are in the U.S., the U.K., Sweden, Belgium, and Finland. "The most important thing when evaluating a contractor is experience in a particular field such as DNA or gene therapy," she said. Company size is also importantsmall ones have more flexibility, larger ones more experience; regulatory expertise on both sides is essential.
In Finland, there are national centers such as BioCity, Turku, and BioMedicum Helsinki, which offer contract research, GMP compliant animal testing, and many other services. But FIT chooses to do all its production in-house because they feel this gives them the flexibility they need to get to clinical trials without being dependent on anyone else.