Regulatory Focus™ > News Articles > New FDA Document Clarifies IND Process for Drugs, Biologics and Biosimilars

New FDA Document Clarifies IND Process for Drugs, Biologics and Biosimilars

Posted 30 April 2013 | By Alexander Gaffney, RAC

A new procedural document issued by the US Food and Drug Administration (FDA) instructs its staff on the best practices-known as Good Review Practices (GVPs)-used in the review of investigational new drug (IND) applications.

INDs are used by pharmaceutical and biotechnology companies at the relative start of the new drug application (NDA) and biologics licensing application (BLA) process, and once approved allow sponsors to begin the clinical testing phase of product development.

The IND is essentially a license to circumvent the Federal Food, Drug and Cosmetic Act (FD&C Act), which otherwise prohibits the interstate movement of any unapproved new drug product, and the process at large is in effect from the issuance of the IND approval by FDA through the NDA or BLA submission by the company. This process is flexible, however, and may include additional marketing applications or trials depending on the submission path(s) taken by the sponsor.

The New MAPP

The New Manual of Policies and Procedures (MAPP) issued by FDA is specifically meant for the Center for Drug Evaluation and Research (CDER), the main regulatory body for human pharmaceutical products and many biological products as well.

While it doesn't address many aspects of the IND process, such as the content of scientific reviews or the conduct of staff therein, it does lay out the specific dates and timelines by which staff are supposed to review an IND application.

Explains FDA: "The ability of CDER review staff and managers to adhere to and consistently achieve these review management principles depends on the availability of adequate resources (e.g., staffing, training, and information technology support). CDER also needs the full cooperation and participation of sponsors for effective implementation of the GRMPs. Therefore, this document describes best practices for CDER review staff, which will be implemented over time as resources permit. It is intended to describe CDER's ultimate goals for review timelines, but does not establish actual review timelines at this time."

At the core of the MAPP is a desire to seek process efficiencies sought by legislators and industry in the FDA Safety and Innovation Act (FDASIA), which calls for FDA to improve the speed at which it reviews and approves applications. "We can accomplish these efficiencies by actively describing and implementing best practices (e.g., in meetings and in timely responses to other sponsor submissions)," FDA explained.

And more than just efficiency, FDA said that consistency would serve to maximize the number of trials that are useful to a product's eventual application, thereby cutting down on development time and costs for sponsors and FDA alike.

MAPP Basics for Industry

The MAPP goes on to list a few core principles by which the entire process must operate if it is to be efficient and consistent. And the process, FDA notes, starts largely with the IND sponsor, whom they said is responsible for maintaining and submitting a "well-organized and complete submission." FDA staff are asked to work to promote the submission of such INDs, but notes that their ability to influence the submission itself can be limited.

Sponsors may also ask CDER officials to look at and answer questions, which should be identified on the first page of the submission. These will be answered if FDA staff have the time to do so, which is not guaranteed.

Further basics of the content of the IND are outlined in the MAPP as well, and cover the target product profile, supporting data, the hypothesis, statistical analysis plan, the trial start date and the marked-up copy (e.g. any protocol amendments).

Sponsors are also advised to cut down on overall regulatory time by identifying key issues and questions, including all important information, the clearly identifying the intent of the submission.

The MAPP also identifies one component of the biosimilar IND submission strategy, which notes that the objective of the development plan is "not to independently demonstrate efficacy and safety." Instead, FDA writes, the objective is to demonstrate "that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components" and that there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity and potency of the product."

The entire guideline, including the timelines for various product application types, may be found here.

FDA: Good Review Practice: Good Review Management Principles and Practices for Effective IND Development and Review

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