May 1, 2008, Vol. 2, No. 18

Biopharmaceuticals: Lack of Information Disclosure Confounds Public Trust, Particularly in the Context of Biosimilars

By Ron Rader
BioWorld Perspectives Contributing Writer

Editor's note: Ron Rader is the president of the Biotechnology Information Institute.

Biopharmaceuticals, particularly those regulated as biologics, are black boxes in terms of useful information that is available about what they are (which is largely based on how they are made). This rules out meaningful transparency, public oversight, and trust in biopharmaceuticals, particularly concerning eventual approvals of biosimilars.

How will any of the concerned communities, including the medical, scientific, pharmacy and advocate/activist communities and patients, ever be informed or assured regarding the identity of products, manufacturing-related product safety and the validity of FDA biopharmaceutical product approvals? And how will there be meaningful public oversight and trust in biosimilars when little or no information will likely be available to allow meaningful comparisons between innovator drugs and biosimilars?

If one accepts that process = product, as propounded by innovator companies in the contest of biogenerics debates, by definition, no one knows what biopharmaceuticals are! When biotechnology processes (involving live organisms) are used, the manufacturing processes, materials and conditions determine the nature and composition of resulting products (with products from different manufacturers inherently unique). However, no one knows much about specific biopharmaceuticals — what they are, which is based on how they are made — because information about manufacturing processes and specifications is not available. Generally, such information is considered proprietary and not disclosed by the manufacturer or the FDA.

The Secrets Surrounding Biologics

Biologics product approvals are inherently secret pacts between the sponsor and FDA concerning the acceptable ranges in variations in manufacturing processes, materials and final specifications that qualify as allowing the final formulated product to be marketed. And nearly all later supplemental approvals involving changes in products and their manufacture are never substantively disclosed by the FDA or the sponsor. Even if useful information was publicly disclosed upon original approval, there is no way to know the extent to which it still applies to the current product.

As author of the only reference book concerning biopharmaceuticals, I can attest that insufficient information is available regarding the identity, manufacturing processes and specifications of most marketed biopharmaceuticals. Considerable effort must be expended to find information from diverse sources, with the resulting profiles almost always lacking some basic information (such as product specifications, which no one discloses) and not being authoritative.

Contrary to the presumptions of many in the scientific and medical communities, manufacturing methods and specifications for biopharmaceuticals are almost never reported in peer-reviewed or other scientific literature. In addition, it is very difficult to derive real-world product-related information from patents. Product inserts/labeling are among the few authoritative sources available, but at best these include only a few sentences or crude, terse descriptions of products. And when information is available, European Public Assessment Report documents are now the most informative source, not anything from FDA or manufacturers.

Biotech Companies: Part of the Problem and Solution

Companies universally assert that all product information is, by definition, proprietary. When asked, PR reps often express fear and avoid providing product information. And most medical information departments have been scrubbed of any information, including published articles, which substantively describe products, their manufacture and specifications. Staff in these departments are often not knowledgeable in the technical sense about what their products are (how they are made, materials used, final specifications, etc.).

There are exceptions to non-disclosure, mostly where manufacturing methods are hyped as part of products' marketing (e.g., plasma derivative manufacturers often disclose detailed information about viral inactivation and purification processes).

Government Processes Discourage Transparency

Looking at the FDA's public approvals-related documentation, there is often not even a single sentence, much less a paragraph or section, presenting information about what the product is, how it is made, final specifications, whether the product tested in preclinical and clinical testing is the same as that approved or now marketed, or whether the FDA-approved product is different than the product marketed in other countries.

For someone looking, what was actually approved is often very unclear. The only information actually identifying or describing what has been evaluated is often the active agent's or product's common and/or trade names.

CMC (chemistry, manufacturing and controls) aspects are much more fundamental and important in terms of safety than results from clinical trials. Pharmaceutical developers in the U.S. are now required to publicly disclose considerable information about clinical trials, their protocols and results, but nothing about the products themselves!

Seemingly endless attention is paid to, and endless information is often available, concerning trials; however, there is usually little useful information regarding manufacturing, purity, potency, consistency and final specifications.

Suggestions for Change

Will there be any meaningful transparency or public oversight and trust in the approval of biologics, particularly biosimilars? The answer is no — not without some changes by industry and FDA, which will probably need to be forced on them by Congress.

I would suggest that those concerned with safety, public trust or the implementation of an effective FDA biosimilars regulatory regime consider pushing for the following: requiring all newly approved biopharmaceutical products to include a sponsor-generated (or FDA-generated and sponsor-approved) public domain, and substantively informative descriptions of products' identity/sources, manufacturing processes and final specifications. This also should be done in an abbreviated fashion for supplemental approvals involving manufacturing/product-related changes. This way, at least there will be some basic information available about what products are at any particular time, and it will be more authoritative information than currently is available.

Disclosing such overviews of CMC aspects will do little to help reverse engineering by biogenerics developers, while advancing knowledge, science and public trust.

With detailed, previously undisclosed clinical trials information now becoming routinely available, it is time for industry to reconsider its antiquated policies toward disclosing descriptive information about its marketed products.

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