"What Is a Generic Biopharmaceutical? Biogeneric? Follow-On Protein? Biosimilar? Follow-On Biologic?"

Part 1:  Introduction and Basic Paradigms

Abstract: The concepts, paradigms, terminology and definitions concerning generic biopharmaceuticals (biogenerics) are still in a primitive state. Use of essentially all current terms may support, denigrate or obfuscate various views and discussions of the topic, e.g., to many 'biogeneric' evokes negative connotations from association with generic drugs and/or suggests that products are identical, rather than similar/related. There are three basic views/paradigms/definitions of generic biopharmaceuticals. Entity-based views concentrate on the products and active agents, including chemical structures and the unique aspects imparted by their biological source/identity, manufacturing process and specifications (process=product paradigm). Regulatory-based views concentrate on biopharmaceuticals as being approved or on track for approval as biogenerics (involving abbreviated filings based on comparative testing, sometimes therapeutic equivalence/substitution). Market/commercial-based views concentrate on products as competing for similar/same indications, having similar names, or any other perceived similarities. Depending on the view/paradigm/definition used and whether one takes a world or just Western (major market)-centric view, there are currently either many (hundreds), some or just a few biogeneric products in commerce; and biosimilars/follow-on biologics/biogenerics have either been around for a century or more, a few decades, a few years or do not yet even exist.

Abstract: Because of their complexity, biopharmaceutical products defy use of various conventional chemical and pharmaceutical information paradigms and methods that work well with drugs and other chemical substances. Before one can deal with biogenerics, difficult questions must be answered, e.g., What defines a biopharmaceutical agent or product as unique and distinct from others?; And, what entity-, regulatory-, and/or market-based changes in an agent or product require it to be considered a new, different one? Biopharmaceuticals will have to be defined, named, and tracked. But how should names be assigned, particularly to biogenerics? Should generic/similar names be assigned, facilitating marketing as generics but likely decreasing safety, or should unique names be assigned, favoring safety but likely decreasing the cost savings generic offer? Both unique and (bio)generic names for both finished products and active ingredients will be required for different uses/users. However, current nomenclature systems are inadequent for biopharamceuticals, e.g., with systematic nomenclature (IUPAC and CAS) designed to index the chemical literature, and nonproprietary pharmaceutical nomenclature (USAN and INN) designed to handle small molecule, particularly generic, drugs. New paradigms, terminology, taxonomy, and nomenclature systems are needed for biopharmaceuticals, particularly ones that include biogenerics. This industry maturation will be painful, requiring industry and regulators to define products, their relationships and develop related information resources and educational programs. The U.S. BIOPHARMACOPEIA Registry of Biopharamceuticals will assist in this process by developing new nomenclature systems, candidate names and a public Registry of biopharmaceutical products.

• Part 1:  (Bio)Technology-Based Definitions - This reviews the four very different basic views/paradigms/definitions of what is a biopharmaceutical, concentrating on technology-based definitions, and the terms and definitions used by U.S. and European Union regulatory authorities.
  
  
• Part 2:  Company and Industry Definitions - This reviews and critiques the views/paradigms/definitions of 'biopharmaceutical' no longer linked to biotechnology, with these aberrant definitions often adopted by many in the financial community, press, companies and even major U.S. trade associations (BIO and PhRMA).

  Abstract - Pharmaceuticals are composed of two major subsets - biopharmaceuticals and drugs (the vast majority). Biopharmaceuticals are pharmaceuticals inherently, usually obviously, biological in nature (e.g., proteins, cells) manufactured using biotechnology (involving live organisms). A derivative view limits this to recombinant proteins. Two other common views/paradigms/definitions ignore linkage to biological nature/biotechnology and take business/market-centric views. These either include as being biopharmaceuticals any/all pharmaceuticals connected with a biotechnology-like (small, entrepreneurial) company or that otherwise can be portrayed as being high-tech; or simply consider all pharmaceuticals to now be biopharmaceuticals (i.e., the drug/pharmaceutical industry is now the biopharmaceutical industry). These later two views are very common, but are dysfunctional, e.g., they arbitrarily include many or even all small molecule and other drugs (pharmaceuticals inherently chemical, not biological, in nature and manufactured by chemical means). With the biopharmaceutical industry lacking its own trade organization representing its interests [and sponsoring projects such as the BIOPHARMACOPIEA], the widespread misuse, cooptation and obfuscation of 'biopharmaceutical' (and 'biotechnology') places the underlying definitions, identity and public perception of the industry at risk to public relations, lobbying and rebranding efforts; and confounds discussions of biopharmaceuticals and related issues, e.g., biogenerics.