Blog # 5 Guidance for Industry: Residual Drug in Transdermal and Related Drug Delivery Systems

Theresa Seiverd
Blog #5

Name of Guidance: Residual Drug in Transdermal and Related Drug Delivery Systems

Status of Guidance: Draft

Release Date: August 2010

Link to Guidance: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM220796.pdf

Target Audience: Pharmaceutical Industry, specifically developers and manufacturers of drug and device combination products

Laws and Regulations Referenced: None

Summary: The transdermal drug delivery system (TDDS), transmucosal drug delivery system (TDMS), and topical patches contains an excess amount of drug substance beyond what is needed to be delivered to the patient. The excess amount is needed to make sure the patient is getting the intended amount of drug. The excess amount of drug in the product has a significant potential to impact the product’s quality, safety, and efficacy. The goal of this guidance is to ensure that the sponsor is applying a risk base approach to the design and manufacture to the TDDS, TDMS, and similar delivery systems.

Rationale: The excess amount of drug that is retained in the TDDS, TDMS, and topical patches raises a potential safety issue not only to the patient, but also to other family members, caregivers, children, and pets. There have been adverse events reported that are related to prolonged drug exposure because the patient did not remove the TDDS or related device. In fact, some children have died from inadvertent exposure to a discarded TDDS.

Recommendation: The FDA recommends that a quality by design approach be implemented in the in the design, development, and manufacture for TDDS, TMDS, and topical patches. The quality by design approach is the subject of the International Conference on Harmonization (ICH) Guidance for industry: Q8(R2) Pharmaceutical Development. It is a risk-based approach to design and development of the product. This approach leads to better understanding of the product and takes into account the patient needs and post use considerations of the product.

The FDA also recommends that a scientific justification to support the amount do residual drug in the TDDS, TDMS, and topical patches to be included in an application. The discussion of this justification can be provided in section 3.2.P.2 (Pharmaceutical Development) of the Common Technical Document. The justification should be sufficient to demonstrate product and process understanding and to ensure that the risks were considered to minimize the amount of residual drug post use to the lowest possible level.

Impact: By applying the quality by design approach to the development of transdermal and similar delivery systems an added benefit is achieved through a higher level of understanding of the product and manufacturing process. Also quality attributes, the product’s characteristics, and patient use are considered very early in the development process and has the result of a better quality product.