In this issue, Wang and colleagues present a new program, the End-of-Phase 2A (EOP2A) meeting, that has been piloted at the Food and Drug Administration (FDA) during the past several years. They describe the details of agency and pharmaceutical industry exchange, which involves a specific focus on the exposure-response relationships of an investigational drug/biological at a time point between completion of phase 1 human trials and prior to extensive phase 2b and phase 3 clinical trials. This meeting involves a detailed examination of available data mapping dose/exposure to efficacy and safety measures using pharmacokinetic and pharmacodynamic modeling approaches. Wang and colleagues share how the FDA pharmacometrics group has undertaken analysis on the data presented by the pharmaceutical industry, communicate their data analysis to the industry sponsor, and facilitate an open and objective exchange of information directed at improving the future drug development approach. They present blinded examples of the multiple different interactions with the industry on different drug development programs. These examples include recommendations around dose, dosing regimens, and clinical trial design. While the experience at the FDA has been limited, the feedback presented by Wang and colleagues suggests a highly valuable experience that in many cases altered the design of the clinical drug development program. The pilot EOP2A meeting that the FDA is exploring is an important part of the fundamental changes that are occurring in modern drug development and part of the FDA's Critical Path vision. Figure 1 displays a vision of drug development that Novartis is currently pursuing to improve predictability, productivity, and efficiency, using the “2 rails” of modeling and simulation and biomarkers to support decision-making in an “explore and confirm” approach for early and late-phase development. The “third rail” of the Novartis approach involves communicating and sharing drug development information with the FDA in an open, dynamic, and interactive manner. The EOP2A program that the FDA has piloted becomes an essential and innovative new vehicle to create the necessary industry/agency communication. While recommendations arising from the EOP2A meetings are not binding to the agency or to industry, there will be a need to ensure that guidance derived from the pharmacometrics group at the FDA is aligned and coordinated with the relevant Medical Review Divisions in the Office of New Drugs that will ultimately oversee the New Drug Application review. . The Novartis concept of drug development, which includes the 2 “rails” of modeling simulation and biomarkers, and the “third rail” of FDA communication. The EOP2A meeting concept advocated by the pharmacometrics group in the Office of Clinical Pharmacology at the FDA addresses gaps in the current state of drug development where data is often compartmentalized and prior knowledge is not used to help guide drug development decision-making. Use of prior knowledge will optimize the design of clinical trials, dose selection, and the patient study populations. Leveraging prior knowledge of disease states and data on similar drugs, as well as information from the sponsor's own drug development program using modeling and simulation, holds the promise of significantly reducing late-stage drug development failures and reducing the cost of drug development. This is in the interest of everyone, including the public, government, and industry. The pharmaceutical industry needs to support the concept of the EOP2A meeting program proposed by Wang and colleagues. While the FDA undertook much of the pharmacometric data analysis and modeling and simulation on industry data in this pilot program, industry should be taking the lead in undertaking this modeling and simulation effort, then presenting the results to the FDA for comment, critique, and review in the next generation of EOP2A meetings. This will facilitate expansion of the program beyond the pilot phase and allow for a “scale-up” of this concept. Further, the FDA should provide a detailed guidance on the EOP2A meeting format and concepts, including how to manage the proprietary nature of data provided by a sponsor that may be used in models prior to approval. We are committed to maximizing the value of the innovative and important EOP2A program that the FDA has created, and hopefully this will be an industrywide response. The “third rail” of communication and data exchange needs to be expanded and used for the ultimate benefit of public health. Financial disclosure: None declared.