Renewal - Investigation of impact of manufacturing difference and formulation variation on drug release for Levonorgestrel Intrauterine System (U01) Clinical Trials Not Allowed

Background:Levonorgestrel-releasing intrauterine system (IUS) is a type of complex drug product with multiple complexities:
it is a long acting product (with drug release up to 5 years), it is locally acting, and it is a drug-device combination product.

There are several IUS drug products on

credit: Flickr


the market; however, there have not been any approved Abbreviated New Drug Applications (ANDAs) so far.

The Agency has previously sponsored a grant (RFA-FD-15-006) with the aim to develop a discriminatory dissolution method for this complex drug product.

Outcomes from this grant include a reliable IUS preparation method, a real-time dissolution method with discriminatory capability, and an accelerated dissolution method.

These achievements now make it possible to conduct a systemic investigation on the impact of critical process parameters (CPP) and formulation variations on the release rate of IUS drug products.

This is a grant expansion of RFA-FD-15-00 6. Upon the completion of this new grant, the results will:
1) deepen the understanding of this complex drug product from a generic drug development perspective, 2) help identify the CPPs and possible formulation variations for this drug product, and 3) inform development of an accurate, sensitive, and less time-consuming BE approach for IUS products.The objective of this study is to identify the CPP and their impact on the critical quality attributes (CQAs), quantitatively determine the impact of manufacturing parameters and formulation variations on the release rate of levonorgestrel of IUSs and estimate acceptable variations on physicochemical properties that do not cause significant changes in drug release rate for this type of complex drug product.

The results from this proposed study will further help the Agency to develop PSGs on IUS products and foster the development of generic IUS products.Objectives:(1) To formulate levonorgestrel IUS products that are qualitatively and quantitatively inequivalent in inactive ingredients (non-Q1/Q2) and evaluate the impact of formulation variations on drug release rates.

The applicant is also encouraged to develop methods that are capable of discriminating polydimethylsiloxane (PDMS) from different sources and different crosslinking density of PDMS.(2) To identify CPPs and CQAs for IUS products and evaluate the impact of CPPs on the CQAs and drug release rates.(3) To conduct dissolution studies, both under real time and accelerated conditions, with two commercially available IUS systems (Mirena and Liletta).

In addition, identify their excipient differences and CQA differences, correlate those identified differences with their levonorgestrel release rates, and provide sufficient evidence for the Agency to estimate acceptable variations on physicochemical properties that do not cause significant changes in drug release rate for IUS products.Additional detail regarding the study objectives listed above:
(1) The intrauterine systems chosen to serve as the reference products for this study include two marketed products, Mirena (levonorgestrel-releasing IUS, 52mg) and Liletta (levonorgestrel-releasing IUS, 52 mg)
Related Programs

Food and Drug Administration_Research

Department of Health and Human Services


Agency: Department of Health and Human Services

Office: Food and Drug Administration

Estimated Funding: $600,000


Relevant Nonprofit Program Categories





Obtain Full Opportunity Text:
Full Announcement

Additional Information of Eligibility:
Eligible Organizations Eligibility is limited to the University of Connecticut

Full Opportunity Web Address:
https://grants.nih.gov/grants/guide/rfa-files/RFA-FD-20-020.html

Contact:


Agency Email Description:
Work Email

Agency Email:


Date Posted:
2020-01-10

Application Due Date:


Archive Date:
2020-04-15



Social Entrepreneurship
Spotlight



Heartsong Ceremonies for Today’s World


Heartsong Ceremonies for Today’s World

Danu  Fox founded Heartsong Ceremonies when she observed the majority of the population no longer go to any kind of formal celebration or gathering. Fox view ceremonies as observances where magic happens. Heartsong Ceremonies aim for just that.




Nonprofit Jobs

  Social Services Jobs
  Education Jobs
  Social Services Jobs
  Executive Director Jobs
  Program Director Jobs





More Federal Domestic Assistance Programs


Antiterrorism Assistance Domestic Training Programs | Public Health Research Accreditation Project | Affordable Care Act (ACA) The Primary Care Services Resource Coordination and Development Program | Technical Assistance Grants | Community Development Block Grants/Entitlement Grants |  Site Style by YAML | Grants.gov | Grants | Grants News | Sitemap | Privacy Policy


Edited by: Michael Saunders

© 2004-2020 Copyright Michael Saunders