Followon Biologics: Paving the Way and Making a Case - FDA’s Draft Guidance and an Update from CEI

More evidence that FDA is serious about becoming more efficient (and using the Internet more effectively):  The Agency will provide, on its web site, draft recommendations on how to design the product-specific bioequivalence studies required for Abbreviated New Drug Applications. In the past, such recommendations were only available when a sponsor requested them, resulting in a time-consuming and unnecessary exchange between Agency and sponsor. For more information, read an update by Anne-Marie Murphy on the FDA Law Blog. The previous post on that same blog cites a paper by Gregory Conko of the Competitive Enterprise Institute entitled "Healthy Competition:The Case for Generic and Followon Biologics." It summarizes, succinctly and clearly, the complex approval and manufacturing issues. The following passages address concerns that name-brand BIO companies and other critics of fast-track approval of followon biologics and biogenerics often raise (then makes the point that all biologics involve these risks): ..."Critics of follow-on biologics often illustrate the importance of these concerns by pointing to one instance in which very serious immune reactions were associated with a manufacturing change to a version of the biotech hormone erythropoietin (Epo) produced by an innovator firm...At least four pharmaceutical companies sell different versions of biotech Epo in the U.S."”though each was approved individually as an "innovator" drug, not as a follow-on product. One known but rare side-effect of long-term Epo use is an immunological response called pure red cell aplasia, in which a small number of patients produce antibodies that attack and effectively neutralize both biotech and natural erythropoietin. After a 1998 manufacturing change, patients taking Johnson & Johnson's Eprex brand Epo began suffering an unusually large number of pure red cell aplasia cases. Johnson & Johnson eventually identified the source of the problem and altered its manufacturing process to correct it. A similar problem also occurred in the early 1980s during the clinical testing of a new human growth hormone formulation by an innovator firm A low-level contaminant in the product resulted in an immune system response that caused extreme pain at the injection site, fever, and other symptoms. But the contaminant had not been detected in either lab testing or pre-clinical animal testing.Of course, even full clinical testing of new drugs and biologics on thousands of trial participants is not always sufficient for spotting potential problems because very rare side effects may only be detected when the product is used by much larger numbers of patients. Nevertheless, the incidents do highlight the special diffi culties associated with re-producing biological products. Still, the fact that these incidents arose with innovator, not follow-on, products should give one pause before condemning out of hand the potential of follow-on biopharmaceuticals. These risks are not unique to follow-ons; they occur in all biological products..."Source: Orange Book Blog, which, with FDA Law Blog, should be "required reading" for anyone involved in, learning about, or attempting to cover the industry and FDA).