Follow On Biologics White Paper

On September 25^th and 26^th 2006 at MIT, the Center for Biomedical Innovation held a symposium with one key topic being Follow-on Biologics.  The constituent’s attending the symposia represented academia, industry, and regulators.  The symposia’s purpose was to identify opportunities for significant transformation, collaboration, and could utilize a Safe Haven environment for sharing information among the constituents.  To this end, the use of Chadwick Rules enabled open discussions on formerly competitive or controversial topics.

Professor Cooney, Department of Chemical and Biochemical Engineering, and Professor Sasisekharan, Department of Biological Engineering, led the group. The participants represented innovators, generic biopharmaceutical companies, academic members, consultants, and scientific and legal experts.   They initiated a discussion around a set of key assumptions affecting Follow-on Biologics, see Attachment 1. The focus for biologics encompassed regulatory guidance and standards, critical safety issues e.g. immunogenecity, and definitions-follow on, equivalency, similar, and economic parameters affecting all stakeholders. The symposia team also identified stakeholders and their interests such as legislators, patients, physicians, regulators, innovators, and follow-on biologic companies.

Follow-on Biologics is hotly debated as key variables affect each constituent and have significance in the quality of healthcare, and to individual quality of life and value to the of shareholder.  Further, economic investments, pricing, patent life are variables which often lead to conflict within the sector.  Professor Cooney stated, “We have over twenty years of experience with biologics and significant advances in analytical tools and methods which enable us to define many former unknowns to ensure greater safety and product reliability.” The participants shared their experience in working with regulators and uniformly felt a need for consistency in the regulatory process.

The current demand for biologics is very significant in addressing a myriad of diseases, patient population specifics, as well as health care costs. However, factors such as formulary pricing, costs of development, regulatory vagaries and pending legislation are of concern. The consortia team shared an interest in defining critical parameters and standards for measuring safety, clinical trials, and in examining specifics such as immunogenecity for both safety and efficacy. Thus, the Center for Biomedical Innovation (CBI) would be desirably suited to consider options that would integrate the constituent’s needs, generate data and focus on improving productivity, lowering cost and offering greater access to safe and efficacious biologics for the public.

There were three fundamental principles elicited from the consortium. First, the concept of a Safe Haven was paramount in the thought process to examine innovative solutions to a complex issue. A second principle was to create a data driven foundation for future regulation and guidance. Professor Sasisekharan cited, “This needs to be a data driven process and we have the tools and talent to extract the data.” A third principle was to build upon this foundation of integrated data and address public policy and legislative issues by understanding the economic impacts via modeling methods.

The symposium team introduced three recommendations for consideration by CBI. The goal was based upon the full breadth of existing experience, engage stakeholders and establish pathways to formulate appropriate and consistent regulatory standards and guidance for all biologics (FOB and innovator).

1.  The initial step would require an integrated database within the safe haven to share safety and efficacy data.
2. In parallel, analyze new scientific and technological approaches that may offer regulatory guidance to address safety and efficacy uncertainties.
3. As a result of the data platform, CBI will create econometric models to address the national and global issues of healthcare legislation factors such as access, cost, risk-benefit consideration, plus regulatory mandates and financial incentives or deterrents.

At CBI/MIT, the FDA recently announced a relationship with CBI for post-marketing Surveillance. The intent would be to share information in a safe haven environment and apply MIT academic resources and expertise to evaluate safety signals on marketed pharmaceutical drugs. Given the nature of this effort, the Follow-on Biologics could append the database and begin to expedite the assessment with data from sources such as the Government Agencies and NDA submissions.  This would be the building block for the subsequent initiatives and leverage the strategic partnership and Safe Haven concept.

As there are over 150 biological products serving a variety of diseases and conditions, it is imperative to address the issues of healthcare costs, global supply, regulations, and investment incentives that sustain the future growing need. “The initial step is the formation of a strategic steering committee. If they would utilize the principles endorsed by the symposia team, it would result in a productive first step,” noted Dr. Frank Douglas, Executive Director of MIT’s CBI.  Consequently, through rapid assimilation of data sources, legislative bodies may have access to unbiased data and expertise. Econometric models will evolve to support future legislation scenarios and offer constructive options for committees to consider.

For Public Health and Public Policy to advance, there is a sense of urgency. Initially, to embrace a Safe Haven concept and create an integrated database, as well as generate valid data, is critical to all constituents. It serves the public interest, the industry and the academic institution. This is an innovative approach to leverage the industry, regulatory, and academia to resolve Healthcare issues. It will encounter resistance with justifiable issues of concern; however, with an intent and sustained vigor, the public interest will best be served as there are very few alternatives addressing and important and timely issue.

Attachment 1:

Key Assumptions

• FDA and Agencies demand consistent manufacturing processes and quality biologic products
• Safety and Efficacy remain paramount
• Comparability
• Aggregation
• Purity
• Process controls – CMC
• Comparability factors are: Immune response; impurities; ROA – dose & frequency; glycosylation; neoepitopes, immuno modulation properties and require standards
• Structure, function, purity require stress testing and quantification
• Battery of Analytical tools enhance measurement, quantitation and detection – qualification
• Potential Mapping of protein, polysaccharides, lipids for fingerprinting facilitates learning
• Glyco form Mapping (glycosylation variance mapping to prognosticate disease progress or state)