Thursday, November 21, 2024 11/21/2024

Assessing the skin pharmacokinetics of topical drugs, and the bio(in)equivalence of topical drug products, using non-invasive techniques

Award Number: U01FD006533
ORGANIZATION: FOOD AND DRUG ADMINISTRATION
OPDIV: FDA
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

The quantitative determination of the bioavailability (BA) of a topically applied drug at its site of action in the skin represents an unmet regulatory need. The majority of dermatological drug targets are found in the epidermis and upper dermis (including appendages such as hair follicles and sebaceous glands), beneath the principal skin barrier, the stratum corneum (SC). While some alternative methods to clinical endpoint BA and bioequivalence (BE) studies have been identified, the evaluation of other surrogate approaches is a ‘work-in-progress’. The central hypothesis of the research strategy proposed is that spectroscopic (in particular, Raman) imaging is able to provide a non-invasive, accurate, sensitive and reproducible determination of the rate and extent to which a topically administered drug becomes available at its site of action below the SC (and, specifically, the viable epidermis). The initial goal is to establish experimental methods, combining Raman and mass spectrometry imaging, to prove this hypothesis ex vivo; subsequently, the objective is to develop Raman imaging in vivo, and to calibrate the approach using complementary techniques. The project has the following specific aims: (a) to conceive strategies by which unambiguous Raman spectroscopic analysis of a drug in the skin can be achieved despite the potential for significant, background signal interference; (b) to evolve a robust approach to correct for drug signal attenuation as a function of increasing depth of measurement in the skin; (c) to demonstrate that continuous, real- time Raman imaging after topical application of a formulation can measure the drug’s “input kinetics” into the viable epidermis ex vivo; (d) to correlate and validate Raman spectroscopic assessment of drug input with parallel, high-sensitivity mass spectroscopic analysis and imaging; (e) to develop Raman imaging to quantify drug input kinetics into the viable epidermis in vivo and to calibrate the method using SC sampling and reverse iontophoresis, another non-invasive method, in combination with mathematical modelling; (f) to demonstrate that the refined spectroscopic tool can characterise the epidermal BA of a topically applied drug and distinguish correctly between formulations that are BE and those that are not; and (g) to apply spatio-temporal mathematical modelling to identify the mechanistic processes underlying the observed results, to explore the impact of drug properties on those mechanisms, and to estimate and validate key metrics of topical bioavailability. In summary, therefore, the proposed project combines different, but synergistic, approaches to assess topical BA/BE with novel spectroscopic imaging strategies to demonstrate that the routine, facile and noninvasive measurement of drug pharmacokinetics in the skin in vivo is an attainable objective with considerable potential for application in regulatory science and decision-making.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF BATH	CLAVERTON DOWN	BATH				GBR	Food and Drug Administration Research	000	5	6/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	UNIVERSITY OF BATH	CLAVERTON DOWN	BATH				GBR	Food and Drug Administration Research	001	5	8/2/2023	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF BATH	CLAVERTON DOWN	BATH				GBR	Food and Drug Administration Research	000	5	12/2/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $249,919 )
2022	2022	UNIVERSITY OF BATH	CLAVERTON DOWN	BATH				GBR	Food and Drug Administration Research	001	5	8/19/2022	NON-COMPETING CONTINUATION	$249,919
2022	2021	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON			GBR	Food and Drug Administration Research	000	4	11/15/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $249,919

Issue Date FY: 2021 ( Subtotal = $249,999 )
2021	2021	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON			GBR	Food and Drug Administration Research	001	4	8/13/2021	NON-COMPETING CONTINUATION	$249,999
2021	2020	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON			GBR	Food and Drug Administration Research	000	3	11/4/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $249,999

Issue Date FY: 2020 ( Subtotal = $249,999 )
2020	2020	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON	BA2 7AY		GBR	Food and Drug Administration Research	001	3	7/24/2020	NON-COMPETING CONTINUATION	$249,999
2020	2019	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON	BA2 7AY		GBR	Food and Drug Administration Research	000	2	12/13/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $249,999

Issue Date FY: 2019 ( Subtotal = $250,000 )
2019	2019	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON	BA2 7AY		GBR	Food and Drug Administration Research	001	2	8/6/2019	NON-COMPETING CONTINUATION	$250,000
2019	2018	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON	BA2 7AY		GBR	Food and Drug Administration Research	000	1	6/19/2019	NEW	$0
														Subtotal = $250,000

Issue Date FY: 2018 ( Subtotal = $250,000 )
2018	2018	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON	BA2 7AY		GBR	Food and Drug Administration Research	001	1	8/29/2018	NEW	$0
2018	2018	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON	BA2 7AY		GBR	Food and Drug Administration Research	002	1	9/14/2018	NEW	$0
2018	2018	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON	BA2 7AY		GBR	Food and Drug Administration Research	000	1	8/27/2018	NEW	$250,000
														Subtotal = $250,000

Grand Total All Awards = $1,249,917

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Assessing the skin pharmacokinetics of topical drugs, and the bio(in)equivalence of topical drug products, using non-invasive techniques

Award Number: U01FD006533

ORGANIZATION: FOOD AND DRUG ADMINISTRATION

OPDIV: FDA

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer