Simplifying the Complex Generics

During the afternoon session at the first annual GRx+Biosims Meeting held in Baltimore, MD, from September 5-7, 2018, a panel discussion was held to deliberate over aspects that are important to consider when developing a complex generic drug product. The panel consisted of FDA as well as generic industry representatives. GDUFA II provides drug manufacturers with several tools to assist in the development of complex generic drug products including enhanced communication opportunities with FDA and opportunities for innovative approaches in developing a complex generic drug. The program is designed to clarify regulatory expectations for prospective applicants early in the development process, assist applicants to bring to the agency innovative approaches in establishing “sameness” and bioequivalence and assure complete submissions for complex product with the goal of promoting a more effective and efficient review process and reduction in the number of review cycles.

The discussion primarily focused on the pre-development meeting process. The main points of discussion were lessons learned, specific considerations for the process relating to pre-GDUFA II complex generics, how much data is enough and optimal timing for submission of data during the pre-development meeting. Topics related to the best way to leverage existing product-specific guidance and propose alternate approaches also came up. The role of controlled correspondence in the complex generic drug development process was also covered by the panel. FDA stated that they have seen high interest in the pre-development meeting program and controlled correspondence process.

The complex generic program is almost a year old and the consensus from the panel was that the industry is generally happy with the complex generic program and the controlled correspondence process but there are still lessons to be learned from the past year. It is important for applicants to understand when a controlled correspondence may be more appropriate than a pre-development meeting request. Controlled correspondence is a faster process and is discipline specific; that is, a controlled correspondence should cover a single issue for a specific FDA discipline. The pre-development meeting process is more appropriate when multiple disciplines are involved. Industry also needs to effectively integrate the communications from controlled correspondence and pre-development, pre-ANDA meeting inputs into their R&D program. Based on this, one of the advice from the panel was to effectively use both pathways and ask the right questions to make sure they get the right advice from the agency.

The discussion clarified that a pre-development meeting is not a consultation meeting. Prospective applicants should have a game plan for their development program and at least pilot data to present to FDA to facilitate a successful meeting. Where applicable, applicants should include alternative plans in their meeting request package rather than bring these up at the last minute in the form of pre-ANDA meetings. FDA encouraged sponsors to come up with innovative alternatives even for products, which already have published guidance for bioequivalence studies.

It was finally concluded that although the complex generic program is rather new and both FDA and industry are still learning, overall the program has been a positive step in the development of complex generic drugs that will provide high-quality, lower-cost alternatives for patients.