By Lynn L. Bergeson
On May 13, 2019, the U.S. Food and Drug Administration (FDA) issued in final guidance designed to assist sponsors in demonstrating that a proposed biological product is interchangeable with a reference product for the purposes of submitting a marketing application or supplement. This would mean that an abbreviated licensure pathway would be created, where biological products shown to be biosimilar to or interchangeable with an FDA-licensed biological reference product may be submitted without intervention. The guidance focuses on therapeutic protein products, providing an overview of scientific considerations in showing interchangeability of a proposed therapeutic protein product with a reference product. It pertains to a series of guidance documents FDA is developing to implement the Biologics Price Competition and Innovation Act of 2009. This final guidance provides sponsors with more certainty on the development of these proposed interchangeable products. Its scope includes scientific considerations of:
- The data and information needed to support a demonstration of interchangeability;
- The design and analysis of a switching study or studies to support a demonstration of interchangeability;
- The comparator product in a switching study or studies; and
- The development of presentations, container closure systems, and delivery device constituent parts for proposed interchangeable products.
By Lynn L. Bergeson
From July 23-24, 2019, the Food and Drug Law Institute (FDLI) will be hosting the Introduction to Drug, Biologics, and Biosimilars Law and Regulation conference in Boston, MA. The conference will cover an overview of administrative agencies that impact these industries and how they interact with the U.S. Food and Drug Administration (FDA). It will also include sessions on the development of drug and biological products, FDA’s review and approval of marketing applications, biosimilars and generic drugs, manufacturing issues, and case studies, among other topics.
By Lynn L. Bergeson
On April 2, 2019, U.S. Food and Drug Administration (FDA) Commissioner, Scott Gottlieb, M.D., and Deputy Commissioner for Policy, Legislation and International Affairs, Anna Abram, released a statement on the status of FDA’s Plant and Animal Biotechnology Innovation Action Plan (Action Plan). Focused on FDA’s risk-based regulatory framework, the Action Plan aims at securing confidence in the safety and performance of plant and animal-based products for consumers, patients, and U.S. trading partners. In his published statement, Dr. Gottlieb emphasizes FDA’s ongoing implementation of the Action Plan, particularly on intentional genomic alterations in animals. Using genetic engineering and genome editing technologies, these innovations are providing additional clarity about how FDA’s regulatory framework works and should continue to work. A key part of the Action Plan’s implementation involves FDA’s Center for Veterinary Medicine’s Innovation Program, which provides sponsors with innovative products based on genomic alterations in animals to benefit from early feedback and guidance.
In the released statement, Abram further highlights the impacts of intentional genomic alterations in animals on human health. DNA editing not only benefits animals by halting animal-to-animal transmission of diseases, but also has the potential to benefit humans. According to Abram, FDA has already evaluated and approved several intentional genomic alterations in animals that produce drugs used to treat human diseases, advance the studies of new drugs, as well as human organ and tissue transplants. The Commissioners state that by ensuring safety of intentional genomic alterations to animals and animal-derived foods, FDA will continue to evaluate the effectivity of these alterations based on the totality of evidence provided rather than from any one particular assessment or result.
On April 25, 2019, FDA’s Center for Veterinary Medicine and the Center for Biologics Evaluation and Research will host a live webinar to discuss policy changes that may improve the Action Plan framework.
By Lynn L. Bergeson
In a recent statement prepared by U.S. Food and Drug Administration’s (FDA) Susan Mayne, Ph.D., Director of FDA’s Center for Food Safety and Applied Nutrition, and by Dennis Keefe, Ph.D, Director of FDA’s Office of Food Additive Safety, FDA highlights its commitment to assisting plant biotechnology developers to foster innovation and ensure that consumers can confidently trust FDA’s high safety standards. Plant biotechnology consists of methods used to introduce new traits or characteristics to a plant (e.g., plants resistant to insect pests, plants with reduced food waste, or plants with reduced levels of harmful elements, amongst others). To assist developers in this field, FDA has a voluntary premarket Plant Biotechnology Consultation Program, which provides developers with the opportunity to engage with FDA to help navigate the appropriate regulatory pathways. The program includes individualized advice from FDA’s biotechnology and food safety experts prior to a plant-based product being permitted to enter the market and allows for biotechnology developers to consult with these FDA experts throughout the entire development, data collection, and evaluation process.
By Lynn L. Bergeson
On March 8, 2019, U.S. Food and Drug Administration (FDA) Commissioner Scott Gottlieb, M.D., released a statement on the continued efforts to advance safe biotechnology innovations, and the deactivation of an import alert on genetically engineered (GE) salmon. In his statement, Dr. Gottlieb emphasized FDA’s mission to evaluate the safety of intentional genomic alterations (IGA) in animals that will ultimately be sold for consumption in the U.S. According to FDA’s recent framework for the efficient development of safe biotechnology products, Plant and Animal Biotechnology Innovation Action Plan, Dr. Gottlieb stated that FDA has taken important steps to help advance new products.
Part of these efforts includes FDA’s 2015 decision to approve an application related to GE salmon containing the first approved IGA in an animal meant for food consumption. In 2016, however, the U.S. Congress directed FDA not to allow into commerce any food containing GE salmon until it issues final labeling guidelines for informing consumers of the GE salmon content in the food. Consequently, in compliance with Congressional views, FDA implemented an import alert in that same year that prevented GE salmon from entering the U.S. With the enactment of the National Bioengineered Food Disclosure Standard (NBFDS) by Congress, the U.S. Department of Agriculture (USDA) was made responsible for the implementation of a mandatory standard for disclosing foods that are bioengineered. FDA was, therefore, divested of its authority over labeling GE content in human foods. Given the Congressional enactment of NBFDS, Dr. Gottlieb stated that FDA believes this Congressional mandate on GE salmon has been satisfied by USDA’s issuance of final regulations implementing NBFDS. NBFDS requires that human food containing GE salmon be labelled to indicate that it is bioengineered. Therefore, FDA has deactivated the import alert that prevented GE salmon from entering the U.S.
By Lynn L. Bergeson
On November 5, 2018, the U.S. Food and Drug Administration (FDA) announced that a proposed collection of information on the Biosimilars User Fee Program was submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995. FDA’s Biosimilars User Fee Program was established under the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), which amended the Public Health Service Act through the addition of Section 351(k). The BPCI Act also amended the Federal Food, Drug, and Cosmetic Act to include Section 351(k) under human drug applications for prescription drug user fees provisions. The Program is meant to “create an abbreviated approval pathway for biological products shown to be biosimilar to or interchangeable with an FDA-licensed reference biological product. This allows a company to apply for licensure of a biosimilar or interchangeable biological product.” In 2012, the Biosimilar User Fee Act (BsUFA) allowed FDA to assess and collect user fees for activities connected with biosimilar biological product development (BPD). Some of these activities include the submission and review of forms, as well as an annual survey of all BsUFA participants.
The information collection proposal estimates an annual reporting burden of 57 hours, based on the number of respondents, the number of responses per respondent, the total annual responses, and the average burden per response. OMB will be accepting comments on FDA’s collection of information proposal until December 5, 2018.
By Lynn L. Bergeson
On October 30, 2018, the U.S. Food and Drug Administration (FDA) published a statement by FDA Commissioner Scott Gottlieb, M.D., and FDA Deputy Commissioner Anna Abram regarding FDA’s new action plan to advance plant and animal biotechnology innovation. Aimed at ensuring the safety of plant and animal biotechnology products and avoiding unnecessary barriers to future innovation, the Action Plan focuses on three key priorities:
- Advancing public health by promoting innovation;
- Strengthening public outreach and communication; and
- Increasing engagement with domestic and international partners.
The statement includes an indication that FDA will be seeking public input in the coming year. Once input is received, the first step in implementing the new action plan will be the adoption of “a comprehensive policy framework for the development and regulatory oversight of animal biotechnology products, including for intentionally genetically altered animals and the food and drug products derived from them.” According to their statement, this policy framework will be modern and flexible, accompanied by two guidance documents in 2019. The guidance documents are intended to provide greater clarity on how FDA will be applying regulatory oversight in evaluating risk profiles of various products. In addition to these elements, the Action Plan also highlights FDA’s commitment to efforts with both national and international partners in fostering efficiency and cooperation.
By Lynn L. Bergeson
On June 21, 2018, the U.S. Food and Drug Administration (FDA) announced it was withdrawing the draft guidance, “Statistical Approaches to Evaluate Analytical Similarity,” issued in September 2017. The announcement states that the draft guidance, if issued in final as written, “was intended to provide advice for sponsors developing biosimilar products regarding the evaluation of analytical similarity between a proposed biosimilar product and the reference product.” Further, comments submitted to the docket “addressed a range of issues that could impact the cost and efficiency of biosimilar development, including the number of reference product lots the draft guidance would recommend biosimilar developers sample in their evaluation of high similarity and the statistical methods for this evaluation.” FDA states that after considering the public comments that were received on the draft guidance, it determined it would withdraw the draft guidance as it gives further consideration to the scientific and regulatory issues involved, and that it intends to “issue future draft guidance that will reflect state-of-the-art techniques in the evaluation of analytical data to support a demonstration that a proposed biosimilar product is highly similar to a reference product.” FDA will communicate publicly when new draft guidance is issued.
By Lauren M. Graham, Ph.D.
On October 12, 2017, the U.S. Food and Drug Administration (FDA) announced two public meetings regarding its Agricultural Biotechnology Education and Outreach Initiative. The meetings will be held in Charlotte, North Carolina, on November 7, 2017, from 8:00 a.m. to 1:00 p.m. (EST) and in San Francisco, California, on November 14, 2017, from 8:00 a.m. to 1:00 p.m. (PST). FDA states the purpose of the public meetings is “to provide the public with an opportunity to share information, experiences, and suggestions to help inform the development of this education and outreach initiative.” This initiative, which Congress appropriated $3 million to fund, calls upon FDA to work with USDA to provide education and outreach to the public on agricultural biotechnology and food and animal feed ingredients derived from biotechnology. More information on the initiative and information on how to register for the meetings is available on FDA’s website. Comments on questions listed in the Federal Register notice, scheduled to be published tomorrow, are also being requested and can be filed in Docket FDA-2017-N-5991 on www.regulations.gov. Comments are due by November 17, 2017.
By Lynn L. Bergeson and Margaret R. Graham
On June 30, 3017, the National Academies of Sciences, Engineering, and Medicine (NAS) released its final version of its report Preparing for Future Products of Biotechnology, which it states “analyzes the future landscape of biotechnology products and seeks to inform forthcoming policy making [and] … identifies potential new risks and frameworks for risk assessment and areas in which the risks or lack of risks relating to the products of biotechnology are well understood.” This report is a collaboration among a committee of experts including the Committee on Future Biotechnology Products and Opportunities to Enhance Capabilities of the Biotechnology Regulatory System (Committee), the Board on Life Sciences, the Board on Agriculture and Natural Resources, the Board on Chemical Sciences and Technology, and the Division on Earth and Life Studies and sponsored by the U.S. Environmental Protection Agency (EPA), the U.S. Department of Agriculture (USDA), and the U.S. Food and Drug Administration (FDA). Lynn L. Bergeson was an external contributor to the Committee’s deliberations and presented before the Committee on the subject of the biotechnology regulatory system.
The report includes sections on emerging trends and products of biotechnology; the current biotechnology regulatory system; understanding risks related to future biotechnology products; opportunities to enhance the capabilities of the biotechnology regulatory system; and an index on congressionally defined product categories that FDA regulates; as well as conclusions and recommendations that were included in our blog item on the prepublication version.
More information on the regulatory issues of biotechnology products is available on our biobased products blog under key word biotechnology, as well as the Bergeson & Campbell, P.C. (B&C®) regulatory developments website under key phrase biobased products, biotechnology.