Saturday, May 8, 2010

Preparation of a New Drug Marketing Application for Clinical Submission

Preparation and the size of a New Drug Application (NDA) are determined by the number of clinical trials required to prove a drug's safety and efficacy. A clinical study involving a drug for the treatment of cancer might require only a few hundred subjects, whereas one involving a drug used for the treatment of cardiovascular disease can require more than 10,000 subjects. Other sections of an NDA that require extensive documentation include sections of preclinical pharmacology, toxicology, carcinogenicity, chemistry, manufacturing and controls (CMC) and information pertaining to the eventual drug label.

The scope of presubmission and clinical submission formal meetings between industry pharma sponsors and the FDA are defined in NDA regulation and guidance documents available at FDA or online at Verbal, frequent communication is strongly recommended between the sponsor regulatory functions and review divisions at FDA.

An End of Phase 2 meeting is strongly recommended with FDA. The minutes of the meeting must be documented, agreed and archived at the sponsor location and FDA. As a rule, correspondence with FDA must be periodically reviewed on the path to clinical submission to ensure completeness of submittable requirements. The timing of the End of Phase 2 meeting is strategic to the advancement of sponsor and FDA understanding of the NDA to be filed. Prior to the End of Phase 2 meeting with FDA, a Briefing Document must be prepared by the sponsor. Included in the End of Phase 2 Briefing Document are key considerations pertaining to the overall preclinical and clinical development plans, adverse events of interest, clinical trial study design, statistical analysis plan, a Q&A section pertaining safety and efficacy findings and a proposed overall clinical submission Table of Contents (TOC). Failure to take full advantage of these meetings with FDA will lead to expensive delays. Communicate with FDA often and with transparency.

The key consideration in preparing an NDA is the number of pivotal clinical trials needed to demonstrate safety and efficacy of a new drug in Clinical Phase 3. With a new drug, 2 adequate and well-controlled clinical trials are generally needed to establish the safety and efficacy of the new drug. For oncology or orphan drugs, however, the acceptability of one pivotal clinical trial may be negotiated with FDA. Considerations pertaining to superiority and equivalence clinical trials must be discussed and agreed with FDA as well and will impact the number of subjects included in the overall clinical submission.

Discussion with FDA early in the NDA process will also aid in the determination of time to clinical submission, time to drug approval, time to market, related costs, capacity and resource considerations. Proper tracking of clinical submission requirements become realistic and achievable. Clinical submission leadership and issue management are more focused and transparent.

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