WASHINGTON, D.C.—The adage says that "close only counts inhorseshoes and hand grenades," and the same measure will now be applied tobiosimilars. But how close is close enough?
In the first glimpse of regulators' thinking on the subject,Dr. Janet Woodcock, director of the U.S. Food and Drug Administration's (FDA)Center for Drug Evaluation and Research, and her co-authors write in the NewEngland Journal of Medicine that theapproval for biosimilars will require a new paradigm of sponsor-FDAinteractions involving analysis of much more data than traditional generics.
Although typically more structurally complex than thesmall-molecule drugs more prevalent in today's market, biologics vary incomplexity from cellular therapies to small, highly purified proteins.
"Unfortunately, access to such products may be limited, notinfrequently because of their cost," the authors state.
To improve access, Congress passed the Biologics PriceCompetition and Innovation (BPCI) Act of 2009, authorizing the FDA to overseean "abbreviated pathway" for approval of biologics that are "biosimilar" toalready-approved products. Utilizing knowledge from the reference products, theabbreviated pathway will eliminate unnecessary testing of biosimilars inanimals and humans.
By way of comparison, in 2009, almost 75 percent ofsmall-molecule prescriptions dispensed in the United States were for generics,and the approval of a generic drug resulted in average savings of 77 percent ofthe product's cost within the first year. Although cost reductions forbiosimilars probably won't be as large, the Federal Trade Commission predictsthat their availability will significantly reduce biologics' cost and increasetheir accessibility, Woodcock and her colleagues say.
"Given the complex nature of biologics, it's unlikely that a'one-size-fits-all' systematic assessment of biosimilarity can be developed.Instead, FDA scientists plan to integrate various types of information toprovide an overall assessment that a biologic is biosimilar to an approvedreference product. Such a 'totality of the evidence' approach can also beapplied to assessing biosimilars, since it seems possible to exceed a currentstate-of-the-art analytic characterization by evaluating more attributes andcombinations of attributes at greater sensitivities with multiple complementarymethods. There may be strategies that allow a 'fingerprint'-like identificationof very similar patterns in two different products. This may involve newtechnologies or improvements in current technologies. The methodology may alsovary depending on the complexity of the biological product being evaluated.Although additional animal and clinical studies will generally be needed forprotein biosimilars for the foreseeable future, the scope and extent of suchstudies may be reduced further if more extensive fingerprint-likecharacterization is used," the authors state.
Drugmakers are keenly interested in the process being mappedout by the FDA, and the agency is currently considering how interactions withcompanies might be structured and how they will affect the user-fee programthat Congress has mandated for biosimilars. As required by the Biologics PriceCompetition and Innovation Act, the FDA is consulting with public andbiosimilars industry stakeholders in developing recommendations for abiosimilars user-fee program for fiscal years 2013 through 2017.
"At the outset of the FDA-biosimilars industry stakeholdermeetings, FDA and industry stakeholders agreed to a set of 'ground rules'governing our discussions," Woodcock tells ddn. "Under the ground rules, the participants will not discuss withexternal parties the issues under discussion in the FDA-industry stakeholdermeetings. The purpose of these ground rules is to promote open and constructivediscussions; in FDA's view, this approach is necessary to produce the best setof proposed recommendations for a biosimilar user fee program. Accordingly, FDAcannot respond to your inquiry. However, following the conclusion of the publicand industry stakeholder meetings, FDA will publish the proposedrecommendations in the Federal Register for public comment. After consideration of such publicviews and comments, FDA will revise the recommendations as necessary beforetransmitting them to Congress."
As is true of other aspects of pharmaceutical development,the advent of a vigorous market for biosimilars will take time. Under the U.S.healthcare law passed last year, brand-name biologic drugs were granted a12-year period of market exclusivity before generic versions can be sold. Themarket is expected to grow from $243 million in 2010 to $3.7 billion by 2015,according to a report from market analysis firm Datamonitor.
