FDA has announced the opening of a docket for interested parties to submit suggestions, recommendations, and comments on a proposed list of biomarkers that were used as outcomes to develop FDA-approved new molecular entities and new biological therapeutics from October 2007 to December 2015. The submissions from interested parties will help FDA determine the utility of the list and may assist FDA in developing databases on biomarkers for drug development. The 60-day window for submitting comments will close on November 18, 2016. The submissions can be either public or confidential.
Specifically, FDA welcomes comments regarding the following two areas:
- Areas of improvement for communicating and disseminating information about biomarkers and their utility as drug development tools.
- The best approach for updating the biomarkers outcomes list, including any modifications of the list, in the future.
FDA Perspective of Biomarkers
The agency has consistently described the importance of biomarkers. A biomarker is “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or biological responses to a therapeutic intervention”. Illustrating their importance, the FDA’s Center for Drug Evaluation and Research (CDER) established the Biomarker Qualification Program to support its work with external stakeholders to develop biomarkers that aid in the drug development process. Through the FDA’s Biomarker Qualification Program, a stakeholder may request regulatory qualification of a biomarker for a particular context of use in drug development.
Biomarkers can be used in a variety of settings, including basic research, drug development, and clinical practice. The Biomarker Qualification Program focuses on biomarkers used in drug development. Once a biomarker is qualified, it can be used in any drug development program under the context for which it obtained qualification. The Biomarker Qualification Program is one of the Drug Development Tools (DDT) Qualification Programs created by CDER to provide a framework for development and regulatory acceptance of scientific tools for use in drug development programs.
Biomarker Challenges in Biosimilar Drug Development
Biologics have transformed the way several diseases have been traditionally treated and managed over the past several years. As patents and exclusivity on several originator biologics are expiring, the industry has been moving in to generate biosimilars. Biosimilars are products that are highly similar to the originator molecules with no clinically meaningful differences in safety, purity and potency.
Owing to the complexity of biological molecules and the variability of sophisticated modern processes by which they are generated, it is difficult to generate fully identical biosimilars. Small structural and functional differences can lead to potentially serious consequences when administered into the diseased host. Regulatory agencies require the generation of physicochemical, structural and functional data on candidate biosimilars prior to approval for use in human subjects. Thus, successful development of biosimilars requires the demonstration of pharmacological similarity with the originator biologics.
MedPAC Supportive of Biosimilar Development
Of particular note, during the last Medicare Payment Advisory Commission meeting, Commissioner Jack Hoadley, a research professor at Georgetown stated, “Unlike the situation where this was discussed in previous years, biosimilars [now] have been approved by the Food and Drug Administration. They're out there. And our goal is to see how to make it easier for consumers to access biosimilars without all the hoops that have currently to be gone through today.”
As reported by Bloomberg BNA, FDA has approved four biosimilars under a 2010 law that created a pathway for such approvals. The agency defines a biosimilar product is a biological product that is approved based on a showing that it is highly similar to an already approved biological product, known as a reference product. MedPAC staffers further noted in a presentation for the commissioners that biologics are large-molecule therapies synthesized from living cells or organisms, in contrast to chemically derived drugs. Biologics are used to treat diseases such as diabetes, rheumatoid arthritis and multiple sclerosis. The staffers stated that biosimilars are expected to reduce costs by 20 to 40 percent.
On further review by the FDA, the biosimilar can be designated as interchangeable with the reference product (RP), which means that a pharmacist could substitute the biosimilar with the RP without a physician's approval. To date, the FDA has not approved an interchangeable biologic drug, only biosimilar drugs.