Question & Answer with Sander Vinks, PhD, PharmD, FCP, Regarding MIDD and M&S
In the ever-evolving landscape of drug development, efficiency, precision, and regulatory success are paramount. Model-Informed Drug Development (MIDD) and Modeling and Simulation (M&S) have emerged as transformative approaches, enabling pharmaceutical companies to optimize clinical trials, refine dosing strategies, and streamline regulatory approval processes. Recognizing the immense potential of these methodologies, the FDA has championed their integration through initiatives such as the MIDD Paired Meeting Program.
To shed light on the impact and future of MIDD/M&S, Dr. Sander Vinks, the leading expert in the field, is sharing insights into the growing applications of MIDD, its role in rare disease research, and why Sponsors are increasingly adopting these data-driven strategies to navigate the complexities of drug development.
What is Model-Informed Drug Development?
As defined by the FDA, MIDD is “an approach that involves developing and applying exposure-based biological and statistical models derived from preclinical and clinical data sources to inform drug development or regulatory decision-making.” FDA is committed to advancing MIDD as a valuable scientific and regulatory tool and one of the developing mechanisms to rely more on digital evidence.
According to FDA, “MIDD approaches use a variety of quantitative methods to help balance the risks and benefits of drug products in development. When successfully applied, MIDD approaches can improve clinical trial efficiency, increase the probability of regulatory success, and optimize drug dosing/therapeutic individualization in the absence of dedicated trials.”
MIDD is also known and referred to as Modeling and Simulation (M&S), a shorter term for the entire encompassment, which refers to the computational mathematical models that simulate data that are then used for decision-making.
FDA MIDD Paired Meeting Program
Further championing the use of MIDD and M&S, in 2022, the FDA created the MIDD Pilot Program to facilitate integrating MIDD into more drug applications and advancing its use in the Prescription Drug User Fee Act VI (PDUFA VI), included as part of FDA Reauthorization Act of 2017 (Public Law 115-52). In 2023, the Prescription Drug User Fee Act (PDUFA VII) as part of the FDA Reauthorization Act of 2023, cemented the pilot program into the MIDD Paired Meeting Program. The MIDD Paired Meeting provides selected Sponsors the opportunity to meet with FDA and discuss MIDD approaches as it related to their product development. The program accepts one to two paired-meeting requests quarterly throughout the PDUFA VII (2023-2027) period. Additional proposals that meet the eligibility requirements and are conducted by FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER).
MIDD FAQ: Question & Answer with Dr. Sander Vinks
What do you find to be one of the most impactful uses of MIDD / M&S for Sponsors’ / clients’ product programs?
Dr. Sander Vinks: I think every aspect of MIDD / M&S is impactful for Sponsors, especially when a Sponsor plans to incorporate MIDD early in development and take advantage of FDA’s MIDD Paired Meeting Program, which provides additional meetings and interaction opportunities with FDA. The FDA greatly champions the use of MIDD and works with Sponsors to refine and define the MIDD aspects of their program.
What areas do you predict will see the most utilization of MIDD / M&S?
Dr. Sander Vinks: I predict that Pediatrics and Rare Diseases will be growing areas where Sponsors request MIDD / M&S assistance for their programs to meet and complete FDA requirements for pediatric trials.
Currently, we see the most requests for MIDD / M&S to help Sponsors optimize their doses for efficacy, therapeutic value, and safety, eliminating the need for multiple trials to test out doses solely based on nonclinical data estimates.
Where do you think MIDD / M&S should be utilized more?
Dr. Sander Vinks: Rare diseases that have the greatest unmet medical needs.
There are hundreds of rare diseases without FDA-approved therapies, which represent the area of greatest medical need. FDA’s CDER promotes the use and has expanded the scope for quantitative medicine to employ disease models (mathematical models of a specific disease’s natural progression without treatment) for multiple applications, including:
- Patient enrichment (as Sponsors often face patient enrollment issues in rare diseases)
- Clinical trial design (using M&S to optimize the trial for the specific rare disease)
- Endpoint selection (help selecting the optimal endpoint to yield a therapeutic response)
- Pediatrics extrapolation
- Late-phase trial design
Do you agree that more Sponsors / clients are shifting to using MIDD / M&S options for their product programs to meet FDA requirements, combat rising prices for clinical trials, shortages in nonclinical testing, and speed up program timelines?
Dr. Sander Vinks: Yes, since the pandemic, there have been shortages in species used for nonclinical testing (mice, cynomolgus monkeys, and nonhuman primates), drug product supplies, and challenges with patient enrollment. Modeling & Simulation provides solutions to these challenges for many Sponsors.
In times of shortages, Sponsors face challenges to accomplish their program development plans. Modeling and Simulation provides alternative solutions for Sponsors that are more time and cost-effective rather than putting their product development plans on hold. For example, if a Sponsor were to encounter a shortage of species in their nonclinical testing plans, Modeling and Simulation could utilize a small data package from the Sponsor to model out and simulate how additional specimens would be affected. This would enrich the Sponsor’s original small data package and provide additional insights for their preclinical and IND-enabling plans. This example is a small facet of the numerous applications and solutions that MIDD / M&S can provide to Sponsor’s development programs.
What would you most like Sponsors / clients to understand about MIDD / M&S and what would be your key message to them?
Dr. Sander Vinks: I would like Sponsors to understand how informative and flexible of a tool that MIDD / M&S is for development programs – both during development and for finding solutions to problems. Many may think that MIDD / M&S is only used early in product development, or can only be used to address certain aspects, such as the evaluation of drug – drug interactions, but in reality, we are able to design and create insightful and mechanism-based models that can assist Sponsors throughout their entire development lifecycle.
My key message to Sponsors and clients would be to explore the value added from MIDD / M&S approaches through conversations with the pharmacometrics experts on ProPharma’s Regulatory Sciences team and by engaging with FDA through their MIDD Paired Meeting Program. Most importantly, FDA champions the use of MIDD / M&S at all stages of the regulatory process and FDA interactions.
Achieve Successful Interactions with FDA with the Right Regulatory Partner
As the pharmaceutical industry continues to embrace innovation, MIDD and M&S stand out as indispensable tools for optimizing drug development, improving clinical trial efficiency, and meeting FDA’s regulatory requirements. By leveraging these advanced methodologies, Sponsors can navigate challenges such as patient enrollment, dose optimization, and rare disease research with greater precision and efficiency.
FDA’s commitment to integrating MIDD into the regulatory landscape, through initiatives like the MIDD Paired Meeting Program, further underscores its value. For Sponsors looking to enhance their development strategies and regulatory success, engaging with experts in MIDD/M&S is a critical step forward. Our team of expert regulatory consultants is ready to assist you throughout the entire process, helping you harness the full potential of these transformative approaches.
