Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Patch adhesion and local tolerability ofTransdermal Delivery Systems
Requirements according to the new draft EMA Guidelines
Dr. Janet SchrieverFederal Institute for Drugs and Medical Devices
(BfArM), Germany
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Transdermal drug delivery systems (TDDS)
Designed to deliver a therapeutically effective amount of drug across a skin into the systemic circulation.
Examples: Nicotine patches Fentanyl and
Buprenorphine patches Hormonal patches
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Draft Guideline on quality of transdermal patchesDeadline for comments March 2013
Annex 2: In vivo skin adhesion
Draft Guideline on the pharmacokinetic and clinical evaluation of modified-release dosage formsDeadline for comments September 2013
Appendix I: Sensitisation and irritation test for transdermal products
NEW
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Generic application
Equivalence testing should comprise bioequivalence, non-inferiority in terms of adhesion, and demonstration of satisfactory clinical safety and local
tolerance.
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – International Symposium on Past Successes, Future Challenges in Paediatric Oncology, May 16, 2008
The adhesive of the TDDS is critical to the safety, efficacy and quality of the product.
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Skin adhesion study
Ensure adhesion equivalence prior to bioequivalence investigations in volunteers.
May be included as a component part of human clinical pharmacokinetic and efficacy studies, or
May be an independent study with either patients or volunteers.
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Skin adhesion study
As a minimum, the smallest and the largest patch sizes should be tested in vivo.
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Assessment of patch area adherence using a 7-point score
Smaller increments allow improved differentiation
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Assessment of patch area adherence
The frequency of assessment should be more than daily, e.g. 0.0 hours (immediately after application), 6.0 hours, 12.0 hours and 24.0 hours (immediately prior to patch removal) after patch
application. The adherent area may be photo-technically recorded (i.e.
digital photographs) at each assessment time point.
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Requirements
Mean adherence > 90% should be expected Poor adherence events should be investigated and possible
causes and risk factors determined. The results should be reported in explanatory tabular and
graphical formats.
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Under discussion: How to assess the adhesion score?
Hold a transparent overlay (pre-printed with a box grid) over the patch.
Mark the area of detachment directly on the overlay.
Avoid re-attachment of the patch to the skin during the assessment.
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Under discussion: How to perform such a study when the proposed to be marketed product includes a non-transparent integrated cover patch?
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – International Symposium on Past Successes, Future Challenges in Paediatric Oncology, May 16, 2008
The condition of the skin may influence the absorption of an active substance from a TDDS and affect the efficacy or safety
of the product.
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Sensitisation and irritation test
Similarity has to be shown for skin irritation and sensitization unless otherwise justified by e.g. very similar quantitative and qualitative composition.
Draft Guideline on the pharmacokinetic and clinical evaluation of modified-release dosage forms (Appendix I) recommends study design and scoring systems
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Overall Study Design for a generic application
Active- and placebo-controlled, multiple-dose, three-phase, parallel-group design.
Evaluation of both cumulative dermal irritation and contact sensitization.
Test, reference and placebo transdermal patches should be applied to randomly assigned test areas on the backs of subjects in two groups (Group 1 and Group 2) .
Trained blinded observer.
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Assessment of dermal response using a 8-point scale
Dermal response scores require that at least 25% or more of the patch area demonstrate an observable response.
"Strong" reaction to the test patch
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Assessment of other effects using a 5-point score
Dermal response scores require that at least 25% or more of the patch area demonstrate an observable response.
"Strong" reaction to the test patch
Federal Institute for Drugsand Medical Devices
Dr. J. Schriever – Patch adhesion and local tolerability of Transdermal Delivery Systems, May 16, 2013
Results
Skin irritation: Compare the test and reference treatments for the mean irritation scores (average numeric dermal response over the observations) and the total cumulative irritation scores (sum of the numeric dermal response scores over the observations).
Skin sensitization: Tabulate dermal response scores ≥2 during the Challenge Phase.