situation in 1986, and it was alsodetailed in a 1986 study,
Biotechnology Nomenclature and InformationOrganization,
by the National Academy of Sciences (
). Two decades later, the situation haschanged little, if any. For example, thereare a large number of relevant research,medical, regulatory, and company information resources, but there is still just one reference source specializing inbiopharmaceutical products (
). Thereare no comprehensive directories orother resources concerningbiotechnologies (e.g., those available forlicensing or used in commerce).Biotechnology and biopharmaceuticalproducts have yet to be integrated intobroader chemical and pharmaceuticalinformation science and resources/systems. Because of their complexity,these products defy use of variousconventional chemical andpharmaceutical information paradigms,methods, and artifices that work well with drugs and other chemicalsubstances. Other factors result in ascarcity of basic informationconcerning biopharmaceuticals. Frommany technical perspectives, suchproducts remain enigmas.
As mentioned, biopharmaceuticalactive agents and products can bedescribed, defined, and consideredunique or related/(bio)generic only through multifaceted or holisticconsideration of their entity (process
product), regulatory (approval), andcommercial aspects. But before youcan define relationships andcommonalities, you must define whata specific, unique, or distinctbiopharmaceutical actually is: Whatinformation makes an agent orproduct unique and distinct fromothers? And, what entity-, regulatory-,and/or market-based changes in anagent or product require it to beconsidered a new, different one? How information resources, particularly higher quality resources at the top of the information “pyramid,” handlebiopharmaceuticals will provide theframework for how everyone perceivesand thinks of such products. The complexity and diversity of biopharmaceuticals complicatesdescribing them and dealing withrelated information. Biopharmaceuticals,as with other commercial products,cannot simply be described or definedfrom a single perspective. In the real world, for most uses, many factorscollectively define products, and eachfactor must be considered. Adequatedescription of a biopharmaceuticalinvolves lengthy text — useless as aname or identifier. The informationneeded to describe a biopharmaceutical varies with the type of product, but itgenerally requires knowledge of itssource (e.g., what protein from whatorganism), structural aspects; the hostcells or expression system used formanufacture; the manufacturingprocess; dosage form/formulation;approval status; and commercial aspects(e.g., manufacturer and marketer).A significant change from anentity, regulatory, or commercialperspective potentially defines a new,different agent or product. At thesimplest or most basic level, a uniquebiopharmaceutical is a specificfinished product, containing a specificactive agent, with its own originalapproval, and manufactured andmarketed by a single company. Butthis simplistic view does not work wellin the real world. Agents, products,manufacturing, approvals, companies,and marketing change and evolve; andregulatory approvals often have littlerelationship to whether products arethe same, similar, or new/different. The same (or similar?) product may be manufactured and/or marketed by different companies, have differentdosage forms/formulations, receivedifferent approvals, have differentnames in different countries, and besold under the same or a different tradename for the same or differentindications.
What Makes Products Different?
For example, does a product become(must it be considered) a new, differentproduct, if its active agent undergoes amajor change — e.g., if the species of host cell line used for manufacture of arecombinant protein is changed? Whatif the product is largely reformulated— e.g., albumin replaced by a sugar asprotein stabilizer? Does it matter whether such changes result only in asupplemental approval becauseregulatory agencies somehow considerthem to be comparable? And what if such changes are never publicly disclosed (which is very common)? What about the same agent in differentformulations (e.g., lyophilized powderand aqueous solution)? When considering entity-baseduniqueness or novelty, should you rely on approvals, which are very inconsistent in this respect (e.g., FDAoriginal versus supplemental biologicsapprovals) and which often are notreported? Whose approvals (whichcountry’s or countries’) do you go by? Isa product manufactured and marketedby one company the same or different when it is simply relabeled and sold by another company under a differentname? Does it matter whether it is soldfor the same or a different indication orin the same or different countries?Some things are fairly clear. Forexample, products with clearly differentactive agents are distinct and/orunique. For many purposes, productsfrom different companies, withdifferent trade names and/or fordifferent indications may be judged tobe distinct. However, in practice, whendealing with real biopharmaceuticals, you encounter just about every permutation of factors involved.Generally, because of the difficulty,these aspects are often ignored or by necessity loosely applied, much as mostcurrent discussions concerningbiogenerics fail to define or apply specific criteria. For example, in theonly biopharmaceuticals reference,products are considered in the same orseparate monographs, with somerelated similar entries largely redundantand some simply referencing othersbased on what works to explain thesituation (
).Products that have received original(full) approvals (BLAs or NDAs, forexample) can generally be assumed tobe unique or distinct from other similarproducts that have received originalapprovals. But the FDA and otherregulatory approvals often do notcorrelate well with entity- orcommerce-based factors. With