Complex Product Development - Trans-dermal

1. Transdermal Generic Drug Product
and Similarity (Q3) Approach
Shrikant Sadashivrao Patil; PhD
HHCL
R & D Manager, Transdermal and Film
Technology.

2. Statutory Requirements for Generic Transdermal Product
Approval
1) Chemistry, Manufacturing and Controls
2) Bioequivalence of drug substance(s)
3) Toxicological data of used excipients like adhesives,
tackifiers, solvents and enhancers.
4) Evidence that the generic TDS products do not have a
greater potential to cause skin reactions compared to
the reference product
5) Verification that the adhesion of the generic TDS is
not inferior to that of the reference product.

3. Statutory Support for Alternative BE Criteria
A 2003 addition to the Federal Food Drug and Cosmetic
Act at Section 505(j)(8)(A)(ii) indicates that –
“For a drug that is not intended to be absorbed into the
bloodstream, the Secretary may assess bioavailability by
scientifically valid measurements intended to reflect the
rate and extent to which the active ingredient or therapeutic
ingredient becomes available at the site of drug action”.

4. In-vitro bioequivalence
Sameness of;
1) Active ingredient and strength
2) Dosage form and route of administration
3) Formulation: Formulation technology ; example in case
of transdermal hot melt and solvent casting
4) Chemical and physical characteristics
a) Molecular weight, Polymorphism, Monomer content of
active ingredients and excipients b) Particle size c)
Rheology/Viscosity d) In-vitro drug release e)Surface
tension, Tack, peel and shear f) Crystallization g) Cold
flow properties h) Adhesion considerations etc.

5. Points to be consider
 Use a risk based approach that considers the
physicochemical properties of the drug product.
 Assessment of sameness of the formulations between
the reference listed drug and the proposed product, i.e.,
Q1, Q2.
 The product should meet the same physicochemical
attributes as the RLD, Q3.
 Identify and quantify all components of the
formulation.
 Compare the proposed product formulation to the
reference product formulation.

6. Points to be consider
 Determine the critical physicochemical characteristics
of the drug product.
 Compare the physicochemical characteristics using
appropriate validated analytical techniques.
 All tests should be as per critical quality attribute's and
with justified level of variation with RLD.
 Number of batches and replicates should be defined
and sufficient.
 All test methods should be validated with justified
acceptance criteria.
 Tests should reflect in vivo performance.

7. IVPT Studies: Statistical support for BE waiver
In vitro BE (In-vitro permeation studies by using skin):
The objective of IVPT is to confirm the “SAMENESS” of the
test and reference products.
Accordingly, this is an evaluation of two products that compares
mean and % cumulative variation, flux of a given parameter.
Both the test and reference products must exhibit comparability
for that parameter.
Residue content is important parameter of IVPT study.
Acceptable specified limit for % difference between test and
reference should be scientifically justified.

8. Conclusion
Similarity approach (Q3) to transdermal patch formulation can be possible if;
 Drug application is local; non systemic absorption.
 Similarity matching of formulation by means of technology, dosing,
strength, patch size, application time, location and ingredients w.r.t RLD.
 Sameness of formulation physical and chemical properties by means of
Assay, Related substances, dissolution, water content, residual solvent(s)
if applicable, Adhesion characterization like peel, tack, shear, Rheology /
Viscosity, crystallization, particle size, monomer content etc.
 Similarity of product drug release by IVRT and IVPT studies along
with residue content limits with scientifically justified number of
studies on different human skin tissues (Race/gender/age etc.)