Re: Docket No. FDA-2010-D-0246: Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems
The Biotechnology Industry Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on the “Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems.”
BIO represents more than 1,200 biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 other nations. BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products, thereby expanding the boundaries of science to benefit humanity by providing better healthcare, enhanced agriculture, and a cleaner and safer environment.
I. Quality-By-Design Should Remain a Voluntary, Alternate Approach:
BIO appreciates FDA’s efforts to provide industry with additional clarity around the Agency’s current thinking and expectations regarding product manufacturing, yet we believe that this guidance document is unnecessary as the key principles contained within are covered by other means, including regulation and guidance (such as design controls under 211CFR 820.30).
In this guidance, FDA not only provides information on what must be achieved (minimize the amount of residual drug substance in the transdermal drug delivery systems (TDDS) and transmucosal drug delivery systems (TMDS) products), but how the company is to achieve that end, namely by implementation of a Quality-by-Design (QbD) approach to product development. BIO generally supports QbD as a voluntary, alternate approach to enhance product quality and manufacturing efficiency, but as described in this guidance it may become unnecessarily burdensome and may not reflect the optimal development process. Indeed, the Quality-by-Design approach as described in International Conference of Harmonization (ICH) Guidance Q8(R2) on “Pharmaceutical Development” is designated as an “alternate” method of development when a manufacturer wishes to claim a “design space”. Specifying this development approach is not consistent with ICHQ8(R2) language which FDA has approved.
While we agree with the goal of minimizing the amount of residual drug that may be available in the delivery device after use, we do not support FDA’s identification of a specific development process. Provided that the end goal is achieved and the development process is scientifically sound, there is no need to specify the use of QbD. The residual drug amount left over on TDDS, TMDS, or topical patches would need to be justified consistent with the need to justify specifications.
II. Environmental Impact Assessment Should Cover Patch Disposal Issues
Finally, the approach outlined in this guidance for minimizing the active pharmaceutical ingredient (API) load in the patch for discarded systems is inappropriate. If risks to public health posed by discarded systems exist, these risks should be discussed in the environmental impact assessment already included in New Drug Applications (NDAs) and Biologic License Applications (BLAs). Specifically, 211CFR 25.40 on Environmental Assessments (EA) states “The EA shall focus on relevant environmental issues relating to the use and disposal from use of FDA-regulated articles”. Where disposal is an issue, handling measures can be suggested, analogous to the use of sharps containers for syringes.
BIO appreciates this opportunity to comment on the “Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems.” Specific, detailed comments are included in the following chart. We would be pleased to provide further input or clarification of our comments, as needed.
Andrew J. Emmett
Managing Director, Science and Regulatory Affairs
Biotechnology Industry Organization (BIO)