US FDA Suggests Using ICH Drug Guidance To Meet Device Quality Requirements for Transdermals
Executive Summary
FDA’s draft guidance on transdermal and topical delivery systems says manufacturers can leverage pharmaceutical development studies principles for device design control requirements.
The US Food and Drug Administration has issued draft guidance spelling out that developers of new transdermal products and topical delivery systems can use principles from an International Council on Harmonisation guideline on pharmaceutical development in lieu of attesting compliance with design control information in the agency’s device regulations.
The guidance is to be released on 21 November, but a prepublication copy was made available on 20 November.
Transdermal delivery systems and topical delivery systems, collectively identified as TDS, are used in a variety of therapeutic areas. Transdermal systems are designed to deliver an active ingredient across the skin and into systemic circulation, while topical delivery systems are designed to deliver the active ingredient to local tissue.
An FDA announcement said both systems present similar manufacturing and quality control concerns and similar risk to patients.
Regulated As Combination Products
These drugs are considered combination products and must comply with Title 21 of the Code of Federal Regulations parts 210 and 211 for drug current good manufacturing practices and part 820, the device quality system regulation.
The guidance says that “design controls (21 CFR part 820.30) apply to drug-device combination products including TDS. Essentially, design control activities should confirm that there are no negative interactions between constituent parts and assure that their combined use results in a combination product that is safe and effective and performs as expected.”
Leverage ICH Principles For QTPP
The guidance suggests it may be possible to leverage many aspects of pharmaceutical development described in ICH Q8(R2) to achieve compliance with design controls.
For example, manufactures can use the Quality Target Product Profile as described in this ICH guideline to demonstrate compliance with the “design inputs” under 11 CFR part 820.30(c), which ensures that the product’s design is appropriate to address the intended use of the product.
The QTPP is a prospective summary of the quality characteristics of the TDS product that ideally will be achieved to ensure the desired quality. As an example, a QTPP can include the in vivo delivery of active ingredient to achieve therapeutic effect.
Manufacturers Should Generate CQAs
The draft guidance also states that “early in the TDS development process,” applicants should generate a list of potential critical quality attributes, or CQAs.
The agency will also allow leeway in using ICH principles in Q8(R2) to verify CQAs are met in the finished product, and may substitute CQAs for design “verification” and “validation” in 21 CFR part 820.30(f).
A CQA is a physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range or distribution to ensure the desired product quality. Knowledge of the QTPP for the product, in combination with prior knowledge, risk assessments or experimentation can be used to develop the list of product CQAs.
Applicants must also submit the results of product characterization studies, skin permeability studies, crystallization studies, and residual drug studies. The draft guidance specifies that residual drug studies should be consistent with the FDA's August 2011 guidance. (Also see "Use QbD to Get Through Rough Patch, FDA Tells Transdermal Makers" - Pink Sheet, 1 Oct, 2011.) These studies address minimizing the residual drugs left in the patches.
In addition, manufacturers should also conduct product adhesion studies in accordance with the FDA's 2016 guidance. (Also see "FDA Guidance Aims to Reduce Adhesion Failures of Generic Patches" - Pink Sheet, 30 Jun, 2016.)
The deadline for public comment is 21 February 2019. All submissions must refer to docket No. FDA-2019-D-4447.