Use of Visual Residue Limits Expanding

Acceptance criteria for pharmaceutical manufacturing equipment as stated in 21 CFR 211.67.b.6 requires visual inspection of equipment for cleanliness prior to use. This is the one inspection all operators should be performing regardless of the sampling and analysis techniques employed as part of cleaning validation or verification.

From start to finish, visual inspections are required as part of good manufacturing processes, with formulators required to visually inspect equipment for cleanliness before beginning formulation work, and analysts performing visual inspections of equipment before taking swab samples for equipment cleaning verification. While there are these GMP requirements for visual inspections of equipment, their use can be expanded to reduce operating costs providing appropriate support exists.

While the FDA’s Guide to Inspection of Validation of Cleaning Processes discounts using visual inspections exclusively for cleanliness determination, there are techniques that can be employed to help expand its application and usage. Visual inspections can be complimented with quantitative instrumental techniques such as swab sampling followed by analysis with HPLC or TOC. Comparisons of data accumulated over time can round out and support usage of visual inspections on expanded terms.

More recently, defensible validation schemes have been developed that were not previously available. Processes now exist for the training and certification of individuals and equipment for visual residue limit (VRL) determination and for visual inspection qualification (VIQ). ERA is pursuing patent approval currently for the VRL and VIQ processes it has developed in conjunction with several industry authorities on the subject.

As recent events indicate, the pharmaceutical and biotech industries are certainly not immune to the very challenging economic climate generated in 2008. As companies pursue sound, defensible opportunities to lower operating costs, it is certain that historical norms will be scrutinized. As part of the cleaning validation and verification requirements companies address daily, efforts to introduce and expand the use of visually clean inspections is expected to be greater than it has ever been in the past.