As a follow-up on yesterday’s article on the road to biogenerics, Food and Drug Administration deputy commissioner Janet Woodcock testified before an Oversight Committee held to examine the prospects and need for a pathway that would allow the FDA to approve safe and affordable generic versions of biotech drugs. Witnesses included representatives of FDA, pharmaceutical manufacturers, scientists, and consumer groups.

During the House Oversight and Government Reform Committee hearing, Woodcock said that while the FDA can currently establish the safety between versions of simple protein-based drugs, it will likely “be a stepwise progression over a decade or so,” before the agency can scientifically verify that a generic version of a complex biotech drug can be substituted for the original. 

The issue comes down to a question of whether generic drug companies would have to conduct clinical trials (and to what extent) before gaining approval. Rep. Henry A. Waxman, D-Calif., along with Representatives Emerson, and Pallone and Senators Schumer and Clinton, have re-introduced H.R. 1038, the “Access to Life-Saving Medicine Act,” which would establish a process through which the FDA will be able to approve generic biologics or biopharmaceuticals.

In summary, H.R. 1038 “Amends section 351 of the Public Health Service (PHS) Act to authorize the Secretary of HHS to approve abbreviated applications for biological products that are ‘comparable’ to previously approved (reference) biological products.”

The current abbreviated pathway described in section 505(b)(2) of the FD&C Act permits an applicant to rely on published literature or on the FDA’s finding of safety and effectiveness for a referenced approved drug product to support approval of a proposed product. A 505(b)(2) applicant must demonstrate that reliance on the previous finding of safety and effectiveness is scientifically justified and must submit whatever additional nonclinical and clinical data are necessary to establish that the proposed product is safe and effective.

The FDA has used this pathway to approve some follow-on protein products including Hylenex (hyaluronidase recombinant human), Hydase (hyaluronidase), Fortical (calcitonin salmon recombinant) Nasal Spray, Amphadase (hyaluronidase), GlucaGen (glucagon recombinant for injection), and Omnitrope (somatropin [rDNA origin]).

However, Woodcock made clear that things won’t go easy absent a drastic change in the law stating that:

Because of the variability and complexity of protein molecules, current limitations of analytical methods, and the difficulties in manufacturing a consistent product, it is unlikely that, for most proteins, a manufacturer of a follow-on protein product could demonstrate that its product is identical to an already approved product. Therefore, the section 505 (j) generic drug approval pathway, which is predicated on a finding of the same active ingredient, will not ordinarily be available for protein products.

To establish that two protein products would be substitutable, the sponsor of a follow-on product would need to demonstrate through additional clinical data that repeated switches from the follow-on product to the referenced product (and vice versa) would have no negative effect on the safety and/or effectiveness of the products as a result of immunogenicity. For many follow-on protein products — and in particular, the more complex proteins – there is a significant potential for repeated switches between products to have a negative impact on the safety and/or effectiveness. Therefore, the ability to make determinations of substitutability for follow-on protein products may be limited.

Not that the FDA has been resting on it’s laurels. As evidence of progress on follow-on protein products, Woodcock noted that :

Because there are many challenging scientific and policy questions about follow-on protein products, FDA has actively promoted a public dialogue on these issues. FDA has held two public meetings (September 2004 and February 2005) and co-sponsored a workshop, in collaboration with the National Institute for Standards and Technology, and with the New York Academy of Sciences (December 2005), to gather input on scientific and technical issues related to follow-on protein products. These meetings resulted in a large number of comments and concerns from the interested parties that have informed our considerations of these issues.

Expect continued arguments over the process as well as the projects savings over current costs.

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