A related issue is whether a follow-on product could be rated therapeutically equivalent to an innovator biologic. Documenting
comparability is quite challenging, said Siegel, but "ensuring interchangeability is essentially impossible." Even with the
added studies, Omnitrope did not get a therapeutically equivalent rating from FDA.
To demonstrate substitutability, Woodcock says that the follow-on sponsor may need studies showing that repeated switching
between the innovator and the follow-on has no negative effects.
The prospect of reduced prices on expensive biotech therapies is the main force behind the push for follow-on biologics. A
coalition of generics makers, payers, pharmacy benefit managers (PBMs), and patient advocates claim that new life-saving drugs
are not worth much if patients can't afford them. The PBM Express Scripts unveiled a report in February projecting savings
of $70 billion over ten years from biogenerics.
However, consulting firm Avalere Health estimates savings of only $3.6 billion over ten years. These analysts claim it will
take years for manufacturers to develop and for FDA to approve new follow-ons, and these products will cost more to test and
produce. If they're not interchangeable, moreover, physicians will be slow to prescribe them. But payers say that even prices
only 10% less will save millions on drugs that cost more than $100,000 a year.
As the political pressure rises to legalize follow-ons, brands are seeking added patent protection. The Hatch-Waxman Act provides
five years of exclusivity before generics can challenge a new drug's patent. In Europe, drugs and biologics essentially are
protected for 11 years, which looks attractive to US innovators, especially small biotech companies. The high cost of developing
new biologics—which the Tufts Center puts at $1.25 billion fully capitalized—and more expensive manufacturing processes warrant
stronger protection from patent litigation, industry claims.
The lead biogeneric bill, which is sponsored by Rep. Henry Waxman (D-CA) and backed by Sen. Hillary Clinton (D-NY), doesn't
address exclusivity. But generic industry leaders appear willing to negotiate patent issues and to pay user fees in order
to move the legislation forward.
LET FDA DECIDE
Dealing with such a wide range of complex biologics requires a flexible regulatory policy, says Woodcock. As with EU regulators,
FDA envisions a case-by-case approach to testing and evaluating comparability of follow-ons. To assist manufacturers, the
agency is developing a guidance to clarify what data it recommends for developing follow-ons of those biologics governed by
the Food, Drug and Cosmetic Act. Additional guidances will address technical issues, beginning with immunogenicity and physical
characterization methods for follow-ons. Establishing an approval pathway for this limited list of biotech therapies would
support policies for approving a broader range of follow-ons.
More immediately, evaluation of these products will be complex and time-consuming, but Woodcock says FDA has the expertise
to make the hard decisions that will arise. Overall, agency officials anticipate a gradual evolution towards follow-ons. While
FDA now has the tools to assess comparability of small peptides, Woodcock explained, it may take a decade to develop similarly
precise methods for evaluating larger molecules.
Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, firstname.lastname@example.org