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By Ajit S. Narang, Rajesh B. Gandhi, and Vishal Nashine

Ajit Narang-final   Rajesh Gandhi-final   Vishal Nashine-final

Increasing time, resource, and competition pressures have necessitated due diligence for acceleration of pharmaceutical, preclinical, and clinical development for several assets. However, acceleration goals of fast-to-first-in-human (FIH) versus fast-to-commercial present very different weightage of decision-making criteria leading to short- and long-term benefits and trade-offs. The counter-balances and approaches to handle such trade-offs are also different for small and large molecule drugs.

For small molecule drugs, enabling phase 1 with a fit-for-purpose formulation such as a drug-in-bottle (DIB) or drug-in-capsule (DIC) approach is well established. In addition, enabled drug delivery approaches such as amorphous solid drug dispersions (SDDs), time-release capsules for oral administration, and solubilized formulations are dosed in phase 1 with only the requirement of a foreseeable path to commercial drug product. In most of these cases, the late stage clinical and commercial drug product presentation is different than the phase 1 formulation.

For large molecule parenteral drug products, fast-to-FIH is generally supported with a platform formulation strategy. However, there is an increasing desire to use the phase 1 formulation in late stages of clinical development, even though the actual commercial formulation may not be the same. In addition to the increasing need to minimize drug development timelines, these front-loading pressures are increasing with the emerging trends in clinical testing of biologicals that involve large adaptive trials with staged expansion phases such that an entire clinical drug development program might occur in a continuum.

Challenges inherent with such front-loading of drug product decisions include the need for concentration flexibility pending dose decision; resource and time constraints working against the in-depth involved QbD-development expected for the commercial product; and integration of device-development pathway and timelines into product development strategy.

These challenges result in decisions that are faced early in product development wherein fast-to-FIH works against fast-to-commercial paradigm, and vice-versa. The session Fast-to-FIH Versus Fast-to-Commercial: Paradigms, Trade-Offs, and Counter-Balances at the 2015 AAPS Annual Meeting and Exposition in Orlando is designed to highlight these emerging paradigms in drug development using some real-life examples. In this session, Earl Dye from Genentech, a Member of Roche Group, will highlight the chemistry, manufacturing, and controls (CMC)/good manufacturing practices (GMP) considerations for expedited development programs, and Rahul Rajan from Amgen will discuss the front loading and bridging considerations in accelerated formulation development of monoclonal antibodies and mAb-based modalities.

Ajit S. Narang, Ph.D., is a principal scientist in the Drug Product Science & Technology Department at Bristol-Myers Squibb. He works for the Parenteral Science Technology function on pharmaceutical development of biologics.
Rajesh B. Gandhi, Ph.D., is a group director in the Drug Product Science & Technology Department at Bristol-Myers Squibb. He leads Parenteral Science Technology, accountable for the late-stage pharmaceutical development of biologics.
Vishal Nashine, Ph.D., is a senior research investigator in the Drug Product Science & Technology Department at Bristol-Myers Squibb with extensive experience in early and late stages of biologics development.