By Benjamin Policicchio, PhD and Suzanne M. Sensabaugh, MS, MBA

Welcome to the fourth and final blog post in our mini-series focused on the 2017 Update to the Coordinated Framework for the Regulation of Biotechnology. In the three previous posts, we provided background relevant to this update, discussed the roles and responsibilities of the primary agencies that regulate biotechnology products, and then provided an overview of the interagency communication and coordination that exists between these primary agencies. In this post, we will discuss one case study provided within the update to help clarify the roles and responsibilities of the three major agencies (Food and Drug Administration [FDA], Environmental Protection Agency [EPA], and United States Department of Agriculture [USDA]) and proposed future reviews of and updates to the Coordinated Framework.

Case studies have been provided in this Update to the Coordinated Framework to aid developers in navigating the regulatory framework starting from research activities in the laboratory, to full commercialization of the product. Though these case studies provide examples, it is stressed that developers should contact agencies at the early stages of product development to help make the regulatory process more predictable. We will discuss one case study as presented in this Update, although the Update itself contains 8 different case studies.

Case study #7: A Hypothetical Genetically-Engineered Rabbit

A brief background of the product is provided: “The rabbit (Oryctolagus cuniculus) genome is genetically engineered to express recombinant human insulin (rh insulin) for use as a therapeutic protein in the treatment of human patients lacking adequate functional insulin. The human insulin coding sequence is controlled by 5’ bovine αS(1) casein promoter sequences direct expression of recombinant insulin protein in rabbit milk. The construct is microinjected into fertilized oocytes and the resulting embryos are transferred to the oviduct of a recipient dam. Once a germline GE animal is identified as a lineage progenitor, it is bred to establish a lineage of GE rabbits used in insulin expression in milk.”

Only the FDA has oversight over this product as the recombinant DNA construct encoding the recombinant human (rh) insulin protein integrated in the genome of the GE rabbits is regulated as a new animal drug by the FDA Center for Veterinary Medicine (CVM) and the rh insulin purified from the GE rabbit milk is regulated as a human drug by the FDA Center for Drug Evaluation and Research (CDER). Each product requires a separate approval.

The developer responsibilities during development (e.g., the laboratory, farm, and clinic) are such that the developer should initiate discussions with FDA/CVM once the lineage progenitor has been identified, upon which the FDA/CVM would open an investigational new animal drug file (INAD) leading to approval pertaining to this GE rabbit lineage.

Sponsors must meet all of the requirements for safety and effectiveness of the new animal drug prior to the approval of the rh insulin. For the rh insulin, the sponsor must submit an Investigational New Drug (IND) application to FDA/CDER prior to clinical trial activities. The developer may seek pre-IND advice as well. If FDA approves the rh insulin product, FDA posts a notice of the approval and provides a summary of the safety information relevant to the approval on its website.

Upon public engagement, the FDA codifies the approval of the new animal drug and publishes a Federal Register notice when the approval is codified. Further, the FDA posts on its website a summary of the information on which this approval was based.

A subsection exists within the Update detailing the timeline and mechanism for the review of and, if necessary, update to the Coordinated Framework. The Biotechnology Working Group will produce an annual report for at least five years on specific steps the agencies are taking to implement the Strategy produced by this Update to the Coordinated Framework and any other steps that are being taken to improve the transparency, coordination, predictability, and efficiency of the regulation of biotechnology products. The Biotechnology Working Group will continue to monitor scientific and technical developments in biotechnology and its applications, and to work with stakeholders to undertake future updates to the Coordinated Framework as warranted.

This concludes this mini-series on the 2017 Update to the Coordinated Framework for the Regulation of Biotechnology. For more information, you can read the 2017 Update to the Coordinated Framework for the Regulation of Biotechnology here:



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Suzanne Sensabaugh

Suzanne M. Sensabaugh has advanced the development of over 130 biologics, biosimilars, and combination products since 2009. She can be reached at