Comments on FDA's Draft Guidance

November 5, 2003

Dockets Management Branch (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, Maryland 20852

Re: Docket No. 2003D-0380, Federal Register: September 5, 2003 (Volume 68, Number 172, pp. 52781-52782)

Dear Sir/Madam:

The Biotechnology Industry Organization (BIO) appreciates the opportunity to comment on the Food and Drug Administration's (FDA's) Draft Guidance for Industry: "Process Analytical Technology -- A Framework for Innovative Pharmaceutical Manufacturing and Quality." BIO represents more than 1,000 biotechnology companies, academic institutions, state biotechnology centers and related organizations in all 50 U.S. states and 33 other nations. BIO members are involved in the research and development of health-care, agricultural, industrial and environmental biotechnology products.

BIO supports the FDA's development of Process Analytical Technology (PAT), and therefore we would like to comment on Line 69 of the draft guidance: ". . . the guidance is currently not applicable to products in CDER's Office of Biotechnology Products." BIO suggests that line 69 be expanded to point toward future guidance for biotechnology products.

In principle, the scientific, risk-based framework of PAT is applicable to biotechnology products. In order to include biologics, BIO suggests that the guidance be further developed to include concepts applicable to products that may have significant microheterogeneity. This would include guidance on the development of specifications including the principles for addressing data obtained from inherently variable biological processes.

Many of the principles of PAT are currently practiced in portions of biotechnology processes (such as buffer preparation, fermentation / cell culture and product recovery / purification). The opportunity exists for further, voluntary applications of PAT across the process platform. While the types of PAT and associated controls might have certain similarities between different products, for biotechnology products they will most likely be very product and process specific. This is in contrast to more traditional drugs, where the tools for process control are likely to be more generalized. These concepts should be included in the training for agency staff.

BIO suggests that during FDA's consideration of the applicability of PAT to biotechnology products, process validation be addressed. Process validation is the documentation of process understanding, control and verification. The role of process validation with respect to PAT should be clarified.

Thank you for your consideration of these comments. Please do not hesitate to contact me should you have any questions.

Sincerely,

Gillian R. Woollett, MA, DPhil
Vice President
Science and Regulatory Affairs