OUTSOURCING Formulated for the clinic
Lisa Caralli, director of science and technology, and Ann McMahon, programme director, clinical supply services and drug product technology interaction at Catalent, outline the benefits of developing drug formulation and clinical supply strategies in parallel.
P
reparing a drug to be suitable for clinical trials is more than just understanding the molecule or chemistry; it is
about developing the best and most stable formulation, but also determining how to get the best investigational medicinal product (IMP) to the patient. Finding the best solution has implications for the manufacturing, packaging and supply chain strategies when progressing a product from early phase development to clinic. Just as the molecule’s chemistry must be considered when choosing a drug-delivery technology, so must the drug’s characteristics and intended recipients when developing the packaging design. The packaging design may then inform decisions on the delivery approach, resulting in an optimised drug product ready for the clinic. There are clear advantages in the chemistry, manufacturing and controls (CMC), and clinical teams collaborating from an early stage optimises the trial materials and maximises the chances of a successful study.
Minimise the risk Companies that offer formulation development, manufacturing and packaging expertise can bring experts together to design the best packaging system for the product, whereas companies with limited access to all the container/closure options available may progress suboptimal solutions. For example, if an active pharmaceutical
ingredient (API) is hygroscopic, the increased moisture may destabilise a tablet product. This is particularly problematic with prodrugs that hydrolyse easily and can lead to recrystallisation of amorphous products, resulting in a loss of solubility, and, therefore, bioavailability. Physical characteristics of the product can also be affected, with increased friability causing tablets to crumble in the container.
32 | Outsourcing in Clinical Trials Handbook
One solution might be to coat a tablet with a moisture barrier, but this adds development time and complexity, and can potentially create chemical incompatibility between the coating and the API. A coating step also adds complexity to the manufacturing process and, if not applied carefully, it might cause the product to become tacky, and lead to defects in the coating layer if the tablets stick to one another. Such factors increase the vulnerability to moisture penetration. If the formulation is a capsule, the increased difficulty of coating can raise the risk of defects. Working with clinical supply service experts could offer a physical – rather than a chemical – solution, such as the use of blister packaging. The risk of defects in either a tablet or a capsule product is greatly reduced, as is the possibility of chemical incompatibilities. Minimising these risks allows the product to progress to the clinic faster and blister packaging may offer further benefits, such as allowing dosing instructions on the packaging strips or protecting the IMP and patient safety through tamper-evident materials or childproofing.
An integrated advantage As a product progresses through drug development, there are advantages to using
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