Conclusions

The PAT initiative encourages the pharmaceutical industry to embrace new analytical approaches with the aim of transforming process development and manufacture. Realtime process monitoring and automated control are essential elements of this transformation, which has the potential to improve product quality, cut production costs and reduce time to market.

This case study highlights the availability, relevance, and benefits of a commercially available PAT solution for particle-size analysis. For pharmaceutical products, particle size is often a critical quality attribute that directly impacts performance and/or manufacturability, so better control delivers significant gains. An on-line system was used to transform a stand-alone manual mill into an automated process unit that will integrate into a manufacturing facility with a distributed control system or statistical process control. The Insitec analyzer used is a proven process solution for real-time particle sizing that additionally meets pharmaceutical industry requirements for clean in place, sterilize in place, validation and 21 CFR Part 11, the federal regulations providing guidelines on electronic records and electronic signatures in the United States.

Qualification of an automated mill with closed-loop control delivers a solution that could potentially be used elsewhere in the company for both pilot- and full-scale operations. Semicontinuous operation with extended run times is a realistic and attractive alternative to conventional batch operations.

Alon Vaisman* is an application development manager at Malvern Instruments, Enigma Business Park, Grovewood Road, Malvern, Worcestershire, WR14 1XZ, UK, tel: +44 (0)1684 892456, fax +44 (0)1684 892789 alon.vaisman@malvern.com
. Yanhui Hu is a principal quality-by-design engineer in the quality assurance division at Abbott Laboratories.

*To whom all correspondence should be addressed.