What facilities, equipment and processes are required when working with HPAPIs and how do these differ from those for traditional APIs?
In addition to the equipment and procedures, chemical processes and unit operations might be different than with traditional APIs. For instance, product drying will be avoided wherever possible and preparative chromatography is commonly used for purification because HPAPIs are often complex molecules and difficult to purify with crystallisation (low yields). Moreover, chromatography allows safe purification because this technique is fully automated and the confinement of highly active compounds is easily maintained.How has pharma's increased use of HPAPIs influenced the development of specialised manufacturing equipment?
A large variety of specialised equipment, such as isolators, glove boxes, highly efficient particle air filters, etc. is now available. However, building HPAPI capabilities requires strong experience in the field in order to design the appropriate installations. Thus, specialised manufacturing equipment alone is not sufficient and the plant should be considered as a whole.
What common mistakes, dangers and challenges should companies be aware of when first handling HPAPIs?
Since no general guidelines have been issued for HPAPI manufacturing, this mastery can only be obtained through extensive and long-lasting experience in handling highly potent molecules. We would discourage any company from handling highly potent molecules for the first time without the support of experts in the field. Manufacturing HPAPIs is not only a question of equipment and procedures, but also a question of know-how and commitment to ensure the safe handling of highly potent molecules.
Does the manufacture of HPAPIs present any specific quality control challenges?
Yes. First of all, the majority of analyses have to be performed in-house since HPAPI analysis is not commonly done on a subcontract basis. As a result, HPAPI manufacturers need dedicated equipment for quality control. Because levels of highly potent impurities must be very low, highly effective analytical equipment and measurement methods are absolutely necessary. Lastly, given the risk associated with the handling of HPAPIs, quality control is subjected to the same constraints as R&D and production, and needs to be performed in the appropriate environment (e.g., lab hoods equipped with glove boxes and HEPA filters) and using very specific procedures.