patch adhesion and local tolerability of transdermal ... · federal institute for drugs and medical...

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



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



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



Generic application

Equivalence testing should comprise bioequivalence, non-inferiority in terms of adhesion, and demonstration of satisfactory clinical safety and local

tolerance.


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.



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.



Skin adhesion study

As a minimum, the smallest and the largest patch sizes should be tested in vivo.



Assessment of patch area adherence using a 7-point score

Smaller increments allow improved differentiation



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.



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.



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.



Under discussion: How to perform such a study when the proposed to be marketed product includes a non-transparent integrated cover patch?


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.



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



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.



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



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



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.



Thank you for your attention, and now –questions!

patch adhesion and local tolerability of transdermal ... · federal institute for drugs and medical...

Documents