美国 FDA MIDD 配对试点计划如何帮助赞助商

Its purpose is to advance and integrate quantitative tools within drug development and regulatory science decision-making. These tools can encompass exposure/response, biological, and statistical models using preclinical or clinical datasets to achieve effective integration. Already, we have witnessed several innovations in MIDD. This is thanks to the 2004 Critical Path Initiative, the FDA’s landmark framework to enhance the probability of drug development success.

More vital advancements for MIDD have recently contributed to evidence of effectiveness decisions. They have also supported advisory committee deliberations on a drug’s benefits/risks based on individual trial data as well as meta-analysis and cross-study quantitative analyses.

Akin to the 2004 Critical Path Initiative and the then introduction of the EOP2a meeting framework, the current MIDD Paired Meeting Program falls under the Prescription Drug User Fee Act (PDUFA VII), under the auspices of the FDA Reauthorization Act of 2023.

The MIDD Paired Meeting Program was created to provide:

• An opportunity for drug developers and the FDA to discuss the application of MIDD to the development and regulatory evaluation of investigational medical products, and
• Advice about how particular MIDD approaches can be used in a drug development program

While MIDD encompasses a wide array of topics, the ones the FDA is critically focused on include

• Dose selection or estimation
• Clinical trial simulation
• Predictive or mechanistic safety evaluation

The latter aspect is crucial as the agency continues to perfect predicting human safety based on credible in vitro and in silico tools and techniques.

Let’s examine some key aspects of this new FDA MIDD paired pilot program.

Since the paired program has basic objectives, conceivably any drug discovery and development asset is eligible. The FDA’s analysis of the areas of impact confirmed this.

About 70% of the programs fall in the Phase 2-3 development space (Figure 1). However, it’s good to see a small number of candidates in the preclinical to translational clinical space.

We believe that the agency is amenable to any modality. Drug developers with unprecedented targets and molecules that they want agency advice on can see significant gains from this program.

As seen from Figure 2, a wide variety of modalities have been the subject of these discussions. Small molecule drugs continue to remain popular. It’s good to see that newer biological drug modalities are also part of these conversations.

In general, the agency is interested in dose selection, clinical trial simulations, as well as predictiveness of preclinical data to assess human risk. In that regard, the topics have been wide-ranging (Figure 3). We would like to see more integrated meta-analyses and broader use of model-based meta-analysis (MBMA) in decision-making.

MIDD is a powerful tool that can improve drug discovery and development decision-making. PubMed includes many examples of the benefits of MIDD.

The International Consortium for Innovation & Quality in Pharmaceutical Development (IQ) surveyed pharmaceutical companies that participated in the agency’s paired meeting program. Their survey concluded that participating sponsors were able to decrease development time and costs. Table 1 captures the benefits of the paired pilot program documented by IQ.

Table 1: IQ participating company member benefits of the FDA MIDD paired pilot program (Reference 2)

In summary, program participants have much to gain from this new FDA mechanism for advice. Drug discovery and development programs have so many challenges, including trial cost, patient recruitment, data integration, and decision-making. Given the complexity of recruiting large trials on time, using MIDD science can help. The agency carving time to ensure sponsors can leverage these innovations is a step in the right direction.

Certara’s MIDD experts have been front and center of the tools, software, and technology. We ensure meaningful returns to our clients by delivering value and quality. For more information on how MIDD can assist in your development program, watch this webinar.