Growing interest in modeling prompts launch of MIE program for generic drugs

Officials from the US Food and Drug Administration (FDA) explained how sponsors can increase their chances of getting accepted into the new model-integrated evidence (MIE) pilot program for generic drug applications. The program, which launched on 1 October, aims to expedite generic drug development.

Liang Zhao, director if the division of quantitative methods and modeling for FDA’s Office Research and Standards (ORS) in the Office of Generic Drugs (OGD), discussed the pilot at an 18 January workshop sponsored by the Small Business and Industry Assistance (SBIA) program.

The goal of the program is to facilitate enhanced scientific communication between generic drug developers and FDA, with a specific focus on using modeling techniques in lieu of conducting in vivo bioequivalence (BE) studies to facilitate generic drug development.

Zhao explained that use of modeling approaches can result in reduced development costs time for firms that no longer have to enroll patients in costly BE studies and can result in getting more precise doses faster than a traditional BE study.

“For industry, these advantages encompass not only time and cost savings but also heightened alignment and clarity, particularly when leveraging Model-Integrated Evidence approaches. This becomes particularly pronounced when a comprehensive understanding of a complex modeling approach cannot be fully achieved through pre-ANDA meetings.,” Zhao said. “From the agency's perspective, adopting MIE approaches brings about operational efficiency in managing multiple products, reduces the number of approval cycles, and fosters the development of an ecosystem with industry to devise effective bioequivalence approaches,” he added.

The program is the generic counterpart of the model informed drug development (MIDD) program launched in 2018 under the Prescription Drug User Fee Act (PDUFA VI). (RELATED: Model-Informed Drug Development: Details on FDA Pilot Project, Regulatory Focus 16 April 2018)

The program also complements global efforts that promote modeling for drug development. In May 2022, the International Council for Harmonisation (ICH) released a widely anticipated timetable detailing its plans to issue general guidance on model-informed drug development (MIDD) approaches in drug development. (RELATED: ICH plans model-informed drug development guideline in 3-4 years, Regulatory Focus 4 May 2022)

Zhao explained that interest in modeling is increasing as evidenced by the growing number of pre-ANDA meetings sought by sponsors that want to use modeling approaches in their applications. The number of these interactions grew from two meetings in FYY 2018 to 15 in FY 2022. According to Zhao, through these meetings, industry seeks FDA input on best practices for implementing MIE, including common model approaches, and addressing complex scientific and regulatory issues.

He further noted that more than 1,750 registrants attended the October 2022 virtual workshop sponsored by FDA and the Center for Research on Complex Generics (CRCG) on the use of modeling approaches to support generic product development.

To particpate in the pilot, packages must focus on MIE-focused approaches for establishing BE that cannot be sufficiently addressed under the existing pre-ANDA and ANDA scientific meeting program.

Complex dosage forms, such as orally inhaled dosage products are eligible for the program. Also eligible are non-complex products where sponsors want to develop complex modeling approaches supporting biopharmaceutics classification system (BCS)-based biowaivers and other BE study waivers that are outside current recommendations.

Also covered are novel data analytics tools such as an equivalence analysis of complex particle size distribution (PSD), new quantitative approaches for sameness assessment, and the application of novel data analytics approaches such as machine learning methodology, for BE equivalence assessment.

FDA will receive meeting requests until enough MIE meetings are held and will evaluate the pilot program at the end of the first year.

Maria Monroy-Osorio the regulatory health product manager for ORS, said that submissions should focus on the proposed MIE bioequivalence approach and include specific technical questions. She said that “you should not submit multiple meeting requests of controlled correspondence for the same development products with the same or similar questions.” FDA will decide whether to accept meeting requests within 14 days of receiving the meeting requests.

Eleftheria Tsakalozou, a senior pharmacologist with ORS further addressed the contents of the meeting package. The package should have a “sufficiently developed” scientific proposal, with relevant meeting questions that are clearly stated. Sponsors should also have adequate documentation of the modeling approach and a “clearly documented” model objective. The assumptions and justifications related to model building should also be included.

Those interested in applying should contact FDA at the MIDD meeting program at [email protected]

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Growing interest in modeling prompts launch of MIE program for generic drugs

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