Choosing oral solid-dosage production processes: Could a classification system help?

A proposal for a drug-product manufacturing classification system (MCS) for oral solid-dosage forms, which would build on the idea of the biopharmaceutics classification system (BCS), was published in January 2015 (1). Written by specialists in the UK’s Academy of Pharmaceutical Sciences (APS) MCS working group, the proposal has been discussed at various industry forums by primary authors Michael Leane, principal scientist at Bristol-Myers Squibb; Kendal Pitt, senior technical director at GlaxoSmithKline; and AstraZeneca’s Gavin Reynolds. The system would gather existing knowledge and experience to categorize and describe the properties of an API that would enable manufacture of a finished drug product with a given processing route. The classification system would complement the BCS and help developers select a process for a given API and/or indicate how an API could be optimized for processing with a given route. “A common understanding of risk would help in choosing a solid-dosage manufacturing process and would provide targets for API particle engineering efforts,” said Leane in an interview with Pharmaceutical Technology.

The processing technologies included in the classification system are, in order of increasing complexity: direct compression (DC), dry granulation (DG), wet granulation (WG), and other technologies (OT), such as melt granulation or liquid or semi-solid-filled capsules, for example. More complex processes can handle a wider range of API properties, but may have more steps or related costs. DC, for example, is the simplest process with only mixing and compression, but unfavorable API particle size and shape may be difficult for DC to handle. MCS would aid API development that seeks to engineer API particles to enable use of the simplest process possible for a given formulation. The MCS can also provide information for negotiations between CMOs and pharmaceutical companies by providing a common understanding of API properties and what might be needed to produce a drug product.

The MCS would also facilitate scale-up to clinical or commercial manufacturing facilities. “The MCS would help ensure that the chosen process is more robust by putting the process in the center of the design space rather than at the edges,” explains Leane.

“If you choose the optimal process, scale-up should be easier and have less risk,” adds Pitt. “A more complex manufacturing process might have less worries about how the API will perform but more potential for troubles with scale-up. In granulation, for example, the wetting step could cause a form change; milling subjects the API to shear, and drying subjects it to heat. There are a lot more steps for something to go wrong.”

The MCS is seen as a simplified starting point that classifies only API properties. Interactions with excipients, for example, were not included in the outline. Although excipient choice can certainly affect a formulation, the working group felt that this might add too much complexity to the system. “Companies can use the MCS to perform their own proprietary, more detailed risk analysis that would include a company’s own knowledge, preferences, and expertise based on their own therapeutic areas,” suggests Leane.

The MCS working group plans to continue its discussions and present their ideas at the FIP World Congress of Pharmacy and Pharmaceutical Sciences (Dusseldorf, Germany, October 2015) to elicit suggestions and thoughts from industry professionals. The authors plan to subsequently publish another paper describing possible refinements to the system. 

Reference
1. M. Leane, et al., Pharm. Dev. Technol. 20 (1) 12-21 (2015).

Article DetailsPharmaceutical Technology
Vol. 39, No. 4
Pages: 30

Citation: When referring to this article, please cite it as J. Markarian, “Choosing oral solid-dosage production processes: Could a classification system help?,” Pharmaceutical Technology 39 (4) 2015.