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Experts at the ISPE annual meeting describe best practices, including containment and production in classified spaces.
Next-generation pharmaceutical manufacturing-which must be more efficient, lower cost, and faster to market, while maintaining or improving quality-was a recurring theme at the International Society for Pharmaceutical Engineering (ISPE) annual meeting (Nov. 8–11, 2015, Philadelphia, PA). Although many discussions focused on the high-growth area of biopharmaceuticals, oral-solid dosage (OSD) is a large volume, globally important segment that is here to stay. The 2015 overall winner of the ISPE Facility of the Year Awards, in fact, is an OSD facility-AstraZeneca China's 533,000-ft2 solid-dose facility built in Taizhou, China for local supply of OSD drugs.
OSD drug manufacturing is mature and has been slow to change, but it is time for OSD manufacturing to embrace next-generation technologies, noted presenters from ISPE's OSD Community of Practice at the annual meeting. This group authored the third edition of the OSDBaseline Guide, Volume 3, which will be published in the first quarter of 2016 (1). The new edition considers new technologies available, such as process analytical technology for controls and instrumentation, and other changes in regulations and best practices, such as automation to reduce the risk of human contamination.
A new chapter in the guide addresses containment and cross-contamination, which are increasingly important in OSD because of the growing use of highly potent APIs. It is important to identify parts of the OSD processing equipment that are crucial for containing potent materials, explained Richard Denk, sales for containment at SKAN, in a presentation. These include direct openings in the process where material transfer takes place, such as API dispensing, as well as equipment such as filters in the deduster, which may need containment when opened for cleaning and maintenance, noted Denk (2). Packaging equipment is another aspect to be considered for containment, because operations such as blister filling could potentially expose product.
Another area addressed by the guide is the growing regulatory pressure to produce OSD drugs in classified space, explained Norman Goldschmidt, vice-president at Genesis, Architects, Engineers and Constructors, in a presentation at the meeting (2). The US FDA doesn't require classification for OSD manufacturing spaces, but the China FDA (CFDA) is looking for Grade D classification, he explained. This is similar to the design standard of ISO-8 "at rest," which is suggested in the World Health Organization (WHO) TRS-961 Annex 5 (3), although Grade D has some additional testing requirements. Achieving this level is not burdensome, but can be achieved with air changes in the range of 5 to 20, said Goldschmidt. The new Baseline Guide does not recommend a specific air change rate, however, because the appropriate number depends on many factors, including the potency and form of the product and dustiness of the process step. Dilution of pharmaceutical powders via HVAC [heating, ventilation, and air conditioning] is not necessarily the best or only way to control contamination, cautioned Goldschmidt, who pointed out that the guide discusses various methods for environmental control and containment, including isolation, closed operations, and automation.
Having a better understanding of new technologies and using them in manufacturing processes will help OSD manufacturers meet regulatory and cost pressures and become more efficient and effective.