RAPS is closely monitoring developments in the Coronavirus (COVID-19) outbreak. See our public safety page for the latest updates.

Regulatory Focus™ > News Articles > 2019 > 11 > FDA Drafts Guidance on Transdermal and Topical Drug Delivery Systems

FDA Drafts Guidance on Transdermal and Topical Drug Delivery Systems

Posted 20 November 2019 | By Michael Mezher 

FDA Drafts Guidance on Transdermal and Topical Drug Delivery Systems

The US Food and Drug Administration (FDA) on Wednesday issued draft guidance detailing product development and quality considerations for transdermal and topical delivery systems (TDS) for new and generic drugs.
The 28-page draft guidance explains FDA’s “current thinking on product design and pharmaceutical development, manufacturing process and control, and finished product control,” in addition to discussing other issues that may impact the performance of a drug delivered via a TDS, including adhesion failure and applied heat.
As their names imply, transdermal delivery systems are meant to deliver a drug through the skin and into systemic circulation, whereas topical delivery systems are meant to deliver a drug locally. FDA says that both systems “present similar manufacturing and quality control concerns and similar risks to patients,” and mostly fall into one of two categories: matrix type and liquid or gel reservoir type delivery systems.
FDA notes that the guidance may not apply to other types of TDS, such as microneedles, active transport TDS or TDS applied to broken skin and advises applicants to focus on matrix type TDS due to “inherent failure modes and safety risks associated with reservoir TDS.”
Drugs delivered via TDS are considered combination products and as such FDA says that requirements for design controls under 21 CFR part 820.30 apply in addition to current good manufacturing practice (cGMP) requirements for combination products.
FDA explains that “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.”
“While quality by design [QbD] and design controls share similar characteristics and goals, the device Quality System regulation (21 CFR part 820) includes specific requirements for design development that manufacturers must satisfy,” FDA writes.
However, FDA offers that sponsors may be able to satisfy those requirements by leveraging pharmaceutical development principles described in International Council for Harmonization (ICH) Q8(R2):
“For example, the Quality Target Product Profile (QTPP) … is similar to ‘design inputs’ (21 CFR part 820.30(c)), which ensure that design requirements are appropriate to address the intended use of the product. Further, studies conducted to verify that the critical quality attributes (CQAs) are met in the finished product may also address requirements for design ‘verification’ and ‘validation’ (21 CFR part 820.30(f), (g)), which ensure that the product’s ‘design outputs’ (21 CFR part 820.30(d)) result in a product that safely and effectively achieves its intended effects).”
Some examples of recommended QTPP elements include in vivo delivery of an active ingredient to achieve therapeutic effect, minimization of residual drug, adherence for duration of wear period, minimization of irritation, chemical and physical stability for shelf life and non-drug substance-related impurities. FDA notes that sponsors may identify other QTTP elements “depending on therapeutic need, patient population, or other functional property requirements.”
FDA also emphasizes that applicants should identify potential CQAs for drugs delivered via TDS early in development, and should “typically include appearance (such as lack of visible crystals), dimensions, uniformity of dosage units, assay, permeation enhancer content, impurities and degradants, in vitro drug release profile, preservative/antioxidant content (if present), peel adhesion, tack, release liner peel strength, shear strength, cold flow, residual solvents, residual monomers, microbial limits, and package integrity.”
The guidance goes on to discuss product and process development for TDS products and the information that should be included in an application for a product delivered via TDS.

Regulatory Focus newsletters

All the biggest regulatory news and happenings.