Can you name three authoritative even somewhat comprehensive sources for information about marketed biopharmaceuticals? Can you name one? Actually, other than this author's book, Biopharmaceutical Products in the U.S. and European Markets, there are no standard reference books, databases or other information resources concerning biopharmaceuticals or other types of biotechnology products and technologies. This situation was described in a 1986 report, Biotechnology Nomenclature and Information Organization, by the National Academy of Sciences (and in papers/presentations by the author - 1989 CABIN presentation; 1988 Amer. Chem. Soc. paper) and has not changed since then.
The scarcity of basic reference sources concerning biopharmaceutical and biotechnology products goes to the very heart of many of the public perception and education problems experienced by the biotechnology/biopharmaceutical industry. How can the public, scientists, physicians, regulators and even those within the industry be expected to learn about and have confidence in these products when there are no resources for even the most basic information, including for those within the industry, and where available, much information is often imprecise, ambiguous or even wrong (requiring knowledgeable evaluation and comparison with other information).
Basic information about biopharmaceutical products that, even for industry experts, is hard or impossible to find and put together (the information included in Biopharmaceutical Products in the U.S. and European Markets, where available):
There are certainly many pharmacopeia, handbooks, compendia, etc., concerning marketed pharmaceutical products. These do an excellent job of presenting product medical/use information. However, none present desired information from a biotechnology perspective and nearly all concentrate solely on medical/use aspects. Most available references handle biopharmaceuticals poorly, treating them the same as drugs/chemicals, failing to provide even basic descriptions of what the products are, and/or simply ignoring/omitting whole classes of products (e.g., vaccines, blood products). Many treat biopharmaceuticals as generic products, presenting information about similar (but distinct/unique) products from different manufacturers in the same monograph, e.g., having a single entry for the multiple hepatitis B vaccines or human growth hormone products. None of these resources include adequate information about the unique scientific, technological and commercial aspects of these products, including descriptions of underlying technologies and the nature of these products, development history, relevant patents and licensing, manufacturing methods, quality control measures, market characteristics, etc.--information required to have even a basic understanding of these commercial products. Also, none of the available resources adequately fulfill a basic registry (authority file) function concerning the identity and sources of these products.
Conventional nomenclature, classification and registry systems generally fail when applied to biopharmaceutical products. Chemical structure/identity-based (e.g., IUPAC, CAS), biological (taxonomic), trade name/trademark; primary, secondary and other structural information (protein and gene sequences); culture collection deposits for organisms and cell lines, and other nomenclature, classification and Registry schemes are individually inadequate to define and identify biopharmaceutical products. These systems are generally imprecise, generic and broad in their actual use -- failing to sufficiently identify/describe the biopharmaceutical active ingrdient or final product -- and generally failing to convey information regarding biological source, manufacture and specifications/quality control that define these agents/products. Most of these systems concentrate solely on one parameter, with this often having little relevance to biopharmaceutical products without inclusion of much other information. Trade names/trade marks are inadequate, with these names changed arbitrarily, e.g., often carried over to new, next-generation products. FDA-assigned (proper) names are actually generic names, with the same name applied to similar products. Similarly, Chemical Abstract Service (CAS) Registry Names and Numbers are also generic in their treatment of biopharmaceuticals, e.g, failing to distinguish between similar but unique/different products from different manufacturers. Protein/polypeptide and gene sequences and culture collection depository numbers for cell lines and genetic constructs only begin to describe products.
Unique and unambiguous identification of biopharmaceutical products currently requires lengthy description and characterization of their identity, manufacture and specifications, often from a number of perspectives and using suboptimal terminology. Such encyclopedic descriptions are provided by Biopharmaceutical Products in the U.S. and European Markets.
The Biotechnology Information Institute (BII) has published Biopharmaceutical Products in the U.S. and European Markets, the first and only reference book (and Web site/database) concerning marketed biopharmaceuticals. See www.biopharma.com for further information. This book, now 1234 pages, essentially cumulates all non-medical information available in the public domain regarding marketed biopharmaceutical products. It concentrates on products' biotechnology and commercial aspects, including details of composition, manufacturing methods, companies involved, patents and technology transfer, regulatory history and status, and marketing. However, the book's contents have not yet been reviewed/confirmed by manufacturers -- ultimately, the only authoritative source for product information -- and the available descriptive information regarding products' identity, manufacture and quality is highly inconsistent (varying from product-to-product), although the best available, by far.
An incredibly diverse array of databases and other information resources provide access to scientific and medical information, e.g., the primary literature, and sequence and genomic data. However, these provide little or no substantive information about actual marketed biopharmaceuticals, e.g., what they are (defined by their chemistry/identity, manufacture and quality control). Often, this information is simply not published in the scientific/medical literature or it is well-hidden within the hundreds of articles likely to have been published concerning a marketed product. There are no or insufficient mechanisms for linking scientific and product or technology information, e.g., no authoritative (peer- or company-reviewed) biopharmaceutical product registry system.
Various NIH and other federal programs have invested vast sums ($billions?) on genomic and other basic biomedical databases, but with no concern or investment in their ability to link to real-world, e.g., product- and technological, information. This includes the National Library of Medicine (NLM), which interprets the National Biotechnology Information Act, which authorized the National Biotechnology Information Center (NCBI), as excluding biopharmaceutical products, technologies and other real-world biotechnology (even though the Congressional hearings concentrated on the contributions of marketed biopharmaceutical products to the nation's health, welfare and economy). Rather, all NCBI funds are devoted to sequence and other genomic database resources. NLM book collection guidelines even explicitly rule out acquisition of references concerning real-world biopharmaceutical technologies and industry, e.g., biopharmaceutical manufacturing technologies.
Many of the observations discussed here also apply to other classes of biotechnology products and technologies. For example, the agricultural and food biotechnology areas similarly lack any useful information resources describing what these products are, who makes them and how, the technologies involved, etc.
Considerable resources--tens of millions of dollars annually--are being spent by industry and government for public biotechnology information and education campaigns. These almost exclusively concentrate on agricultural and food biotechnology, with few, if any, concentrating on more mainstream and important healthcare-oriented biotechnologies (dominated by biopharmaceuticals). This is despite biopharmaceuticals constituting the great majority (80%) or more of biotechnology by most parameters, including product sales, number of companies, employment, etc. The many public information/education campaigns and resouces are largely redundant -- seemingly perpetually redeveloping and recycling the same general, non-technical information to the same lowest common denominator audiences. No resources are targeted to provide substantive technical or other information about biotech/biopharmaceutical products and technologies. Without access to supporting technical and other information allowing those interested to learn more about products and technologies, public information/education efforts will ultimately fail. This situation further raises the question, If those within the (bio)pharmaceutical industry can't find adequate substantive information about marketed products/technologies (which is often the case), how can anyone else ever be expected to?
Authoritative technically-oriented information resources about biotechnology and biopharmaceutical products and technologies are desparately needed to complement and support public information/education efforts; and for those in the scientific and industrial communities. The current situation of a severe lack of authoritative (including peer/company-reviewed) technical information sources detracts from public information/education efforts. A top-down or trickle-down approach needs to be included in these efforts. Information resources need to be available for those most knowledgeable in the field (to support a tickle-down effect). Otherwise, the scarcity of product- and technology-specific information will persist; critics and detractors will go unanswered; and the public and even those within the industry will continue to lack access to information to support judgements about the quality, safety, societal impact and other aspects of these complex products and technologies. It is also easy to envision scenarios where lack of information access contributes to liability and other legal problems and restrictive regulation of industry.
Biologics were exempted from various laws/regulations starting in the 1970s requiring the identification (registration) of substances and products in the marketplace, and the reporting of introduction of new substance/products in commerce (e.g., Toxic Substances Control Act inventory). Thus, neither FDA nor industry has ever been mandated to or otherwise bothered to publicly uniquely and unambiguously identify these products. Various substance/product registry systems do not adequately cover biopharmaceutical active agents and products/formulations. For example, the Chemical Abstracts Service (CAS) Registry System often fails to include entries for distinct products; mixes up active agents and formulated products; and/or groups different products (e.g., from different manufacturers) together in the same entry.
In many respects, other than the book, Biopharmaceuticals in the U.S. and European Markets, information resources in the biopharmaceutical area have not advanced for decades. The state of the infrastructure of information resources concerning biopharmaceutical (and other biotechnology) products may be compared with that of chemical, other product and toxicology information decades ago. Prior to the mid-late 1970's, there were very few chemical/product and toxicology information resources available, and substances/products in commerce were not uniquely and unambiguously identified. Federal information activities mandated by the Toxic Substances Control Act (TSCA), the National Cancer Act, and other societal efforts to regulate and define chemical substances in commerce from the mid-1970's to the present have resulted in a very healthy array of chemical, product and toxicology information resources. Similarly, scientific resources in the life sciences, especially the biomedical sciences, have flourished and a healthy array of information resources developed, many with federal support. However, times have changed, and federal mandated efforts in biopharmaceutical product/technology information are not appropriate, likely or desireable. It's now up to industry to get its own house in order.
The incredible masses of published information are often of little or no use in describing biopharmaceutical products. The peer-reviewed and other scientific and medical literature generally contain little or no substantive information about the products they discuss, often simply referring/using (like FDA documentation) a trade or other name to identify products. Publications from early development phases tend to provide more active agent/product descriptive information, but the relevance of this information to the marketed product introduced years later is often unclear. For example, there are recombinant proteins that were initially manufactured in one expression system (e.g., E. coli) and tested through early phase trials, but with Phase III testing and the marketed product being a different product, produced in a different expression system, e.g., mammalian cells. Such substantive product changes during development, particularly changes in expression systems, host cell lines, etc. are becoming more common. Those not using Biopharmaceutical Products in the U.S. and European Markets or otherwise knowing this would have no reason to even suspect this from examination of the literature (with medical/clinical articles often including little information about the agents studied), product inserts, or other information sources.
Patents contain a wealth of information, often including detailed information about products' chemistry/identity and manufacture. However, patents rarely explicitly cite or provide examples, culture collection deposits, sequences, processes, etc., linked explicitly with actual commercial products or technologies. This is particularly true for more recent U.S. patents, with court precedents regarding presentation of 'best mode' allowing overloading of patents with examples, culture collection deposits, etc., with no designation of those most relevant to actual commercial use. Even those knowledgeable are left to make subjective judgements regarding the relevance of information in patents to marketed products.
Product inserts/labeling, in many respects, are the only truly authoritative source for biopharmaceutical product information! These are official FDA, high quality, carefully crafted documents originally prepared by the manufacturer and, unlike most other commercial product information, kept up-to-date. However, these documents are designed for healthcare providers and generally contain only minimal information about the product, its source, manufacture, specifications/quality control, etc.
Manufacturers/marketers are, ultimately, the only source for authoritative information about marketed biopharmaceuticals (with FDA and other regulatory agencies being derivative sources). However, manufacturers/marketers may often be characterized as black boxes or black holes in terms of descriptive product information. Cmpany information gatekeepers (e.g., public relations and medical information departments) generally fail to provide substantive product information. There is a prevalent assumption (misconception) in industry, particularly within the larger and more established companies, that all product (vs. medical/use) information is proprietary, even information previously disclosed, published and touted by the company in press releases. Ironically, generally the longer a product has been on the market and the more established the product and company, the less substantive descriptive information is available about the product. Thus, little or no useful information is often available from many of the largest pharmaceutical companies concerning the longest and most-used products, particularly vaccines and blood products. This includes universal vaccines required to be administered to all infants and other persons in the U.S.; and other products similarly perpetually suffering from public mistrust and misinformation.
The most common response from company PR/press offices requested to provide "readily available, public domain, e.g., published, information" about their products is crude/rude neglect (i.e., no response, not even to written requests). They apparently hope the requestor will simply go away. When inquiries are followed up, company spokespersons commonly revert to acting stupid. They act as though they don't understand the request, as though such a request for product (vs. medical/use or company) information is totally alien/unheard-of, and/or repeat overly simplistic questions, effectively halting communication. Some company spokespersons have even refused to provide product inserts, promotional literature, prior press releases, etc. In recent decades, essentially all products and manufacturing processes can be presumed to be substantially, if not fully, disclosed in and protected by patents (that's what they are for). However, when asked, hardly any company spokespersons will even consider a request to identify exemplary patents related to marketed products (even after being reminded of earlier press releases touting their patents), providing the common response that this is proprietary information. Similarly, when asked for reprints or bibliographies of articles describing their products (vs. their medical/use aspects), the common response is none/neglect or that such information is not available for release. Such practices may have been acceptable in earlier decades, when FDA Summary Basis of Approval (SBA) and other review documents and even advisory committee public meetings included substantive discussion of chemistry, manufacturing and control (CMC) aspects, i.e., when substantive descriptive product information was disclosed by FDA in the public domain. However, with FDA's current practice of often not even mentioning CMC aspects in public review documents, it is up to industry to disclose some some minimally descriptive information.
The databases and literature collections of many company medical information departments have been scrubbed of all references to product descriptive information (concerning chemistry/indentity, manufacture, quality control). This is often to such an extent that these offices freely admit not being able to provide a description of what their biopharmaceutical products are (beyond the scant information in product inserts/labeling).
Failure of companies to provide product information arises from corporate culture sorely in need of fixing/correction, with most information gatekeepers simply assuming all product (vs. medical/use) and technology information to be trade secrets. Whatever the reasons for corporate fears/paranoia and nondisclosure of nonproprietary product/technology information, these probably no longer apply. The (bio)pharmaceutical and biotechnology industries appear not to have (re)examined policies and practices concerning product and technological information disclosures for decades. These policies have clearly not been reexamined in the context of biopharmaceuticals being the most highly complex, high tech, high visibility and often controversial products. Combine these factors with FDA no longer being a source for substantive product information, and one has the recipe for a potential public trust/relations disaster!