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Pharmaceutical Technology APIs, EXCIPIENTS, AND MANUFACTURING eBOOK 2021 35 and the cleaning and maintenance of the facility. Staff must be trained and educated on safe work- ing practices along with ongoing monitoring of the facility to ensure its continued compliance with regulations and design protocols. Hardwall containment For ma ximum containment when processing HPAPIs, a hardwall approach is the most effective, and can enable facilities to handle OELs as low as tens of nanograms per cubic meter. In these scenarios, micronizers can be installed within isolators purged with nitrogen for enhanced manufacturing safety, eliminating the risk of dust explosion for compounds with low minimum ig- nition energy values. The size of the facility can be up to commercial scale, and can provide better efficiency by utilizing continuous milling opera- tion, eliminating the need to stop and change out raw material or micronized drums. An automated washing system can be included to reduce operator intervention, as well as options to accommodate f lexible sampling schemes without the need for external equipment. Such a system requires significant capital expen- diture, but gives a very high degree of automation, is highly efficient at protecting operators, and is designed to give maximum external environmen- tal protection from the HPAPI. Other benefits include accurate control of temperature and rela- tive humidity, and the capability to operate under controlled light- ing conditions when processing light-sensitive compounds. Assessing outsourcing needs For developers looking to choose an outsourcing partner for HPAPI drug development, it is crucial to assess the needs of the project in terms of end result, but where safety is paramount, the invest- ment and operating practices of a company are a top priority. Finding a partner that has the expe- rience, infrastructure, and capabilities to handle projects as development progresses can help re- duce the risk of projects being delayed and im- pacting the success of a commercial launch. With the growing number of drugs that are being developed considered potent or highly potent, the outsourcing industry has adapted, and there has been large-scale investment among service compa- nies to accommodate the need for manufacturing with HPAPIs. What is also known is that HPAPIs have formulation challenges in terms of solubility and dose uniformity, and micronization can play a key part in ensuring these new drugs can be deliv- ered effectively to patients. Its applicability to HPA- PIs in terms of yield efficiency, scale up capabilities, cost-effectiveness, and regulatory understanding means micronization is a solution that can assist at early stage development and continue throughout a drug's journey towards commercialization. PT Figure 1. The "onion skin" design philosophy. FIGURE COURTESY OF THE AUTHORS.