Thursday, November 21, 2024 11/21/2024

Development of Real-Time and Accelerated Dissolution Methods for a Long-Acting Levonorgestrel Intrauterine System

Award Number: U01FD005443
ORGANIZATION: FOOD AND DRUG ADMINISTRATION
OPDIV: FDA
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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SUMMARY/ABSTRACT There are four levonorgestrel-releasing intrauterine systems (LNG-IUSs) approved by the U.S. FDA. However, to date, there are no approved generic LNG-IUSs. Development of LNG-IUSs is challenging: 1) long acting (up to 5 years); 2) locally acting; and 3) drug-device combination products. Under our U.S. FDA grant (RFA-FD-15-006), we have successfully developed and optimized a processing method for qualitatively and quantitatively (Q1/Q2) equivalent LNG-IUSs using Mirena® as the reference product. Physicochemical characterization methods, and a reliable real-time release testing method with discriminatory capability, have been developed. This allowed determination of the impact of drug particle size, physical structure (dimensions and configuration of the device) as well as the source of the outer membrane on in vitro drug release. We have also established accelerated testing methods using hydro-organic media. With these methods in hand, the next logical step to enable development of generic equivalents of the LNG- IUSs is to understand the design space of LNG-IUSs based on the quality target product profiles (QTPPs). Accordingly, it is now necessary to systematically investigate the impact of critical process parameters (CPPs), formulation variations, and the device physical structure (dimensions and configuration) on the release profiles. This will require the development of non-Q1/Q2 equivalent LNG-IUSs, since Q1/Q2 equivalent formulations are limited in terms of the composition and concentration of the excipients. Over the past two decades, our laboratory has made considerable contributions to the formulation development and in vitro release testing (both real- time and accelerated) of many different long-acting complex parenteral drug products. In collaboration with the FDA, we have developed appropriate in vitro approaches to enable bioequivalence recommendations for these complex parenteral drug products, through evaluation of the impact of raw material attributes, as well as processing and formulation parameters on their performance. Building on this knowledge, it is now proposed to develop a manufacturing method for LNG-IUSs suitable for adaption to commercial manufacturing that will allow identification of the CPPs and evaluation of their impact on the critical quality attributes (CQAs). The influence of processing parameters, formulation variations and device physical structure on the release rate of LNG-IUSs will be quantitatively determined. In addition, a robust accelerated release testing method will be developed to reduce the time for in vitro performance testing. Liletta® (a similar product to Mirena®) will be investigated as a second commercial comparator. This research will facilitate the establishment of bioequivalence recommendations for generic LNG-IUSs.


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 = $115,000 )
2024	2024	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	000	10	8/28/2024	NON-COMPETING CONTINUATION	$115,000
2024	2024	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	001	10	8/29/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $115,000

Issue Date FY: 2023 ( Subtotal = $115,000 )
2023	2023	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	000	9	8/11/2023	NON-COMPETING CONTINUATION	$115,000
														Subtotal = $115,000

Issue Date FY: 2022 ( Subtotal = $300,000 )
2022	2022	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	000	8	8/19/2022	NON-COMPETING CONTINUATION	$300,000
														Subtotal = $300,000

Issue Date FY: 2021 ( Subtotal = $300,000 )
2021	2021	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	001	7	8/30/2021	NON-COMPETING CONTINUATION	$300,000
2021	2019	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	000	5	11/25/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $300,000

Issue Date FY: 2020 ( Subtotal = $425,000 )
2020	2020	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	001	6	5/18/2020	COMPETING CONTINUATION	$425,000
2020	2019	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	000	5	5/7/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $425,000

Issue Date FY: 2019 ( Subtotal = $45,000 )
2019	2019	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	000	5	8/6/2019	NON-COMPETING CONTINUATION	$45,000
														Subtotal = $45,000

Issue Date FY: 2018 ( Subtotal = $45,000 )
2018	2018	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	000	4	7/18/2018	NON-COMPETING CONTINUATION	$45,000
														Subtotal = $45,000

Issue Date FY: 2017 ( Subtotal = $70,000 )
2017	2017	UNIVERSITY OF CONNECTICUT	438 WHITNEY RD EXTENSION UNIT 1133	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	000	3	8/8/2017	NON-COMPETING CONTINUATION	$70,000
														Subtotal = $70,000

Issue Date FY: 2016 ( Subtotal = $170,000 )
2016	2016	UNIVERSITY OF CONNECTICUT	438 WHITNEY ROAD EXTENSION	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	000	2	8/25/2016	NON-COMPETING CONTINUATION	$170,000
														Subtotal = $170,000

Issue Date FY: 2015 ( Subtotal = $170,000 )
2015	2015	UNIVERSITY OF CONNECTICUT	438 WHITNEY ROAD EXTENSION	STORRS	CT	06269	CAPITOL	USA	Food and Drug Administration Research	000	1	9/1/2015	NEW	$170,000
														Subtotal = $170,000

Grand Total All Awards = $1,755,000

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Development of Real-Time and Accelerated Dissolution Methods for a Long-Acting Levonorgestrel Intrauterine System

Award Number: U01FD005443

ORGANIZATION: FOOD AND DRUG ADMINISTRATION

OPDIV: FDA

AWARD CLASS: COOPERATIVE AGREEMENT

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

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