Evidence map›Paper›PMID 33547863›Full record

ReviewCPT: pharmacometrics & systems pharmacology2021

Physiologically-based pharmacokinetic modeling to support bioequivalence and approval of generic products: A case for diclofenac sodium topical gel, 1.

Eleftheria Tsakalozou, Andrew Babiskin, Liang Zhao

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in CPT: pharmacometrics & systems pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 70 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Eleftheria TsakalozouDivision of Quantitative Methods and Modeling (DQMM), Office of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Andrew BabiskinDivision of Quantitative Methods and Modeling (DQMM), Office of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Liang ZhaoDivision of Quantitative Methods and Modeling (DQMM), Office of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
United States Food and Drug Administration · USCenter for Drug Evaluation and Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Establishing bioequivalence (BE) for dermatological drug products by conducting comparative clinical end point studies can be costly and the studies may not be sufficiently sensitive to detect certain formulation differences. Quantitative methods and modeling, such as physiologically-based pharmacokinetic (PBPK) modeling, can support alternative BE approaches with reduced or no human testing. To enable PBPK modeling for regulatory decision making, models should be sufficiently verified and validated (V&V) for the intended purpose. This report illustrates the US Food and Drug Administration (FDA) approval of a generic diclofenac sodium topical gel that was based on a totality of evidence, including qualitative and quantitative sameness and physical and structural similarity to the reference product, an in vivo BE study with PK end points, and, more importantly, for the purposes of this report, a virtual BE assessment leveraging dermal PBPK modeling and simulation instead of a comparative clinical end point study in patients. The modeling approach characterized the relationship between systemic (plasma) and local (skin and synovial fluid) diclofenac exposure and demonstrated BE between the generic and reference products at the presumed site of action. Based on the fit-for-purpose modeling principle, the V&V process involved assessing observed data of diclofenac concentrations in skin tissues and plasma, and the overall performance of the modeling platform for relevant products. Using this case as an example, this report provides current scientific considerations on good practices for model V&V and the establishment of BE for dermatological drug products when leveraging PBPK modeling and simulation for regulatory decision making.

Indexed as

Models, BiologicalTherapeutic EquivalencyAdministration, CutaneousAnti-Inflammatory Agents, Non-SteroidalDiclofenacHumansSkinAnti-Inflammatory Agents, Non-SteroidalDiclofenac

Identifiers

PMID33547863
PMCPMC8129718
OpenAlexW3128371112

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.