www.biopharminternational.com March 2018 BioPharm International eBook 7
Outsourcing Resources Complete Response Letters
Avoiding Complete Response
Letters
CRLs put the brakes on drug development and damage corporate
reputation and stock prices. Upfront investment and better sponsor
oversight are ways to prevent them.
AGNES SHANLEY
C
omplete response letters (CR Ls) have
become a powerful way for FDA to push
drug developers to improve their prod-
uct and process understanding during
early development phases. By pointing
out failures discovered during FDA plant preapproval
inspections (PAIs), whether issues involving current
good manufacturing practice (cGMP) compliance or
methods used to establish product safety or efficacy,
CRLs stop the approval process until those problems
are remediated. For companies that have received
them, CRLs have resulted in significant loss of investor
confidence and tumbling stock prices.
The purpose of a CRL, as its name implies, is to
provide sponsors with the "big picture," explains
Christopher Smith, an independent consultant with
the FDA Group. Before using them, FDA would han-
dle everything in a piecemeal way, he says, and spon-
sors would get deficiency letters from the various
disciplines within FDA (e.g., chemistry, clinical, bio-
equivalence, labeling, statistics, etc.) and might also be
notified there was a "facility issue."
During the process, it sometimes seemed to sponsors
that FDA wasn't communicating well internally. So
FDA now uses a CRL to pull everything together and
tell the sponsor where everything stands.
Hanna
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