Monday, June 8, 2009

Filling a niche

Many small biopharma companies in drug discovery outsource the production of materials for early stage clinical trials. Susan Birks visited the new facilities of Bodycote Prova in Camberley, UK, that are designed to tap into that niche

Production of investigational medicinal materials is often small scale but highly regulated Production of investigational medicinal materials is often small scale but highly regulated

It is a long, complicated path for any new drug candidate from that ‘eureka!’ moment of discovery to the final delivery onto the market. The path is beset with hurdles, not the least of which is the years of careful experimental analysis and clinical trials needed to ensure the drug is effective and safe. Such trials require small volumes of the candidate drug materials to be produced and pre-tested under hygienic and controlled conditions.

Bodycote Prova has for some time run a contract pharmaceutical operation that offers drug formulation, analytical and regulatory services for the pharmaceutical and biotech industries. The Camberley-based business has recently opened a purpose-built manufacturing and packaging facility for clinical trial materials. The company has built on to its existing facilities, which mainly comprise labs designed for analytical and formulation development.

Directive 2003/94/EC makes Good Manufacturing Practice (GMP) for clinical trial manufacture a legal requirement. It basically requires manufacturers to follow Volume 4 of the European Guide to GMP. In particular, Annex 13 Manufacture of Investigational Medical Products, attached to Volume 4 of the European Guide to GMP, details instructions in relation to the production of clinical trial materials in Europe. It is also the tool used by the European regulatory authorities when inspecting manufacturing activities.

With ever more effective and, therefore, potent drug materials being discovered, the need to minimise all cross-contamination is key. However, the full potency and sensitising potential of a new material may not always be fully understood during development, so the design of equipment and the acceptance levels used after cleaning need to reflect the nature of these risks.

With its new facilities, the company intends to specialise in the manufacture of investigational medicinal products for early stage clinical studies. Once the materials have been produced, Bodycote Prova can also carry out the work essential to turning the active ingredient into a drug that will be useful to patients.

Gill Clarke, development director responsible for formulation development, regulatory and clinical trials, explains : “As our clients come up with drug compounds, we help support them with intermediates for production of the active pharmaceutical ingredient (API) and then API itself. We will develop the first analytical methods to support both the API and related substances. These will be used to release that drug substance and generate the stability data.

“Following on from that we develop the methods that support the formulated product and carry out the appropriate level of validation to support a regulatory submission and ongoing testing.”

Because time to market is of the essence in drug development, the company aims to get into such studies in the quickest time possible by developing a formulation that is quite simple compared with what might end up on the pharmacy shelf.

“For an oral product it may be a solution or suspension of a drug or a capsule. It is not often a tablet in the early stages – tableting usually comes later on.

“If it needs to be a parenteral we can produce either a solution in an ampoule or a vial. We have a freeze-drier, so that if it is not very stable in solution, we can produce it as a freeze-dried cake that can be reconstituted at the bedside.”

New cleanroom suites

Work on the company’s new cleanroom suites started in February 2008. The rooms, now complete, are designed for the small-scale production of non-sterile products, such as capsules, creams, ointments, gels, oral solutions and suspensions under cGMP.

The suites enable the company to produce quantities of materials up to about 10 kg or 10,000 units – ample for such early stage development where companies often want only around 100 units.

Despite producing non-sterile materials, the cleanrooms have been designed with many of the features used in sterile manufacture, such as appropriate cleanroom clothing, and flush, easy-to-clean surfaces and floors. The rooms also have positive air pressure to prevent ingress of contamination from the corridors.

Windows that look in from the corridors enable visitors to view operations without disturbing the production processes, thus reducing any risk of accidental contamination entering the rooms.

Investigational medicinal products frequently require packaging in an individual way and labelling requires particular care. Within the new complex, Bodycote has the facilities to pack and label the materials ready for delivery.

Following the new build, the company has successfully achieved its MHRA licence and is already finding interest in its services from pharma and biotech, with many new clients from bio-incubators, university spin-outs and small companies that have discovery chemistry but no other lab facilities.

With the market becoming far more competitive, and Big Pharma making cuts, outsourcing has become a growth area. As a result, many new companies are setting up manufacturing facilities that meet the legal requirements for production of clinical trial materials – so high quality facilities and good service are prerequisites.

“Flexibility, quality of service and technical input has always helped us in getting repeat business,” says Clarke, and as competitiveness increases and drug profits decrease, clients are looking for quality of service – they want the job done once, and done right,” says Clarke.

Main services carried out at the Camberley site

• Pre-formulation services
• Salt selection
• Solubility studies
• pH stability profiles
• Excipient selection

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