Transdermal, transmucosal and topical drug delivery patches contain a larger amount of drug than is administered to the patient. The excess facilitates delivery but has led to adverse events, including children dying, and consequently there is a desire to minimise residual drug.
In draft guidance the US Food and Drug Administration (FDA) recommends that scientific justification to support the quantity of residual drug is included in an application.
This information should demonstrate product and process understanding. It should also show that a scientific, risk-based approach has been taken to reducing residual drug. Also, residual drug in a newly developed system should not exceed quantities found in similar FDA-approved products.
While recognising the role the drug surplus plays, the FDA believes approaches can, and should, be taken to reduce residual drug while maintaining the desired therapeutic release rate.
Alterations to formulation, design and system components can all impact on drug delivery and the quantity of residual drug. In particular, the FDA highlights penetration enhancers, self-depleting solvent systems and choice of adhesive.
The type and concentration of excipients, drug load, adhesive thickness and design of the backing layer can also impact on residual drug.
In the draft guidance the FDA also states that adopting the principles of quality by design (QbD), a scientific, risk-based, and proactive approach, can help patch manufacturers reduce residual drug.
Adopting QbD can drive continual improvement of the product throughout its lifecycle to ensure it meets patient requirements and post-use considerations. For manufacturers of drug delivery patches this can help create products that deliver the optimum dose while minimising excess.
Further benefits of QbD include greater understanding of the manufacturing process. For patch producers this can help assess performance characteristics, such as drug permeation, adhesion and application site reaction, as well as product quality attributes.
The FDA states that QbD is applicable to new products and reformulations. Comments and suggestions regarding the draft guidance should be submitted in the next 90 days.