2021 LS&HC Horizons - Flipbook - Page 71
Life Sciences and Health Care Horizons 2021
71
Complex generics
In the brackish waters between drugs and
biologics lies a diverse class of innovative
drug products with an important common
denominator: they are difficult to copy. Referred
to in the EU as “non-biologic, complex drugs,”
and called “complex generics” by FDA, the
original generic drug laws did not contemplate
these products.
Complex generics include (1) Complex Active
Ingredients, such as low molecular weight
heparin, peptides, nanoparticle iron, complex
mixtures, natural source products, (2) Complex
Formulations, such as liposomes, microspheres,
copolymers, (3) Complex Routes of Delivery/
Locally Acting Drugs, and (4) Complex DrugDevice Combinations.
Under the Drug Competition Action Plan
and GDUFA II, FDA is authorized to invest
substantial research dollars into solving the
problem of adapting the generic drug approval
system to fit these complex substances. In 2020,
FDA established the Center for Research on
Complex Generics at the University of Michigan
and the University of Maryland.
Complex generics can be inordinately difficult
to manufacture and characterize. In addition
to pharmacokinetic studies, they may require
extensive in vitro, pharmacodynamic, clinical
and other data. The question is whether these
kinds of data are capable of showing “sameness”
and bioequivalence; and whether FDA has the
authority to review the data under a generic drug
application. Unlike the biosimilars pathway –
which contains an expectation that uncertainties
between the test and reference products will be
addressed with new clinical data – for complex
generics there is no such provision.
In addition to establishing “sameness” for
inherently complex substances – particularly
natural source products and synthetic peptides
– many complex products (e.g., combination
products and long acting depots) raise
bioequivalence study issues. FDA has been
working on a variety of in vitro models to relieve
generics from having to conduct lengthy in vivo
studies, but the validity of these models remains
unresolved.
These types of products have gained attention
from high end generic sponsors, who see an
opportunity to enter as a lone generic, or a
lone 505(b)(2) competitor, where the norm for
most generics is to enter as one of many in a
crowded field.
David Fox
Partner, Washington, D.C.
david.fox@hoganlovells.com
Jason Conaty
Counsel, Washington, D.C.
jason.conaty@hoganlovells.com
