METHODS
Financial Inclusion Criteria
For a branded protein pharmaceutical product to have any value to a potential biogeneric manufacturer, it must have an adequate
potential for economic return to justify the significant investment required to develop the biogeneric mimic. We arbitrarily
selected $20 million as the minimum annual product sales for any branded product to justify developing even the simplest of
biogeneric mimics. This figure errs, if anything, on the side of including some products that may not be economically feasible
targets, but it was decided that providing a comprehensive list was of greater value than providing an incomplete, but highly
selective list.
The starting data set for this analysis, therefore, consisted of a list of all pharmaceutical products (including protein
and small-molecule products) for which the 12 full months' worth of US sales data from September 2004 to August 2005 was at
least $20 million.11 From this preliminary list, all protein and peptide products were identified and retained, while all small molecule products
were removed from consideration.
Exclusion Criteria
Table 1. Classes of products excluded from consideration
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Once the list of all protein and peptide products with annual sales of at least $20 million was prepared, products that fell
into the categories listed in Table 1 were removed. The specific reasons for removing each category from consideration are
provided in the table, but the more general rationale is that these types of products have not been part of the mainstream
discussions of biogenerics. These excluded products represent either classical biological products that clearly fit within
the literal PHSA definition of "biological products" and have remained under the jurisdiction of CBER, or highly specialized
situations not amenable to generalized regulatory guidance. Excluding such products from this analysis is not meant to suggest
that they cannot be genericized, but simply highlights the fact that they have not been considered in the recent discussions
of biogeneric products.
Recent Public Discussion
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The products remaining on the list at this point were consistent with the focus of recent public discussions, which have been
about developing biogenerics for well-characterized (or at least well-characterizable) recombinant DNA and natural source
target products. (For more on the discussions see the sidebar.)
Data Consolidation
The final adjustment to the list of biogeneric targets was to group redundant entries together as if they were single products.
The first criterion used for this grouping was to consolidate entries for products that were deemed therapeutically equivalent
(A-rated) in FDA's Orange Book.12 The second criterion was to consolidate all products from a single manufacturer containing the same active ingredient; the
rationale was that the same active ingredient from the same manufacturer, though used in different finished products, ought
to be the same.
The result of these consolidations, therefore, was a list in which each entry contains a unique active ingredient. This approach
was taken in part to avoid undue weighting of some products, particularly insulins, for which several distinct formulations
are available from a given manufacturer using a single active ingredient.
Product Attributes Each product on the final list of biogeneric target products was examined for a variety of characteristics, including filing
mechanism (NDA or BLA), number of amino acid residues, major chemical modification (glycosylation, PEGylation), source (synthetic,
rDNA, or native DNA), expression system (where appropriate), and whether the product bears a current A-rating (indicating
therapeutic equivalence) in FDA's Orange Book.
Table 2a. Biogeneric target products with annual US sales > $20 million
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Most of this information was derived from package inserts for the products, although some was obtained from other sources,
such as publicly disclosed product approval or licensing information available through FDA's Freedom of Information Act (FOI)
Office, and scientific publications.
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