CBER has innovated further with documents
entitled ‘Points to Consider’. These rank below
guidances in terms of their gravity. These are
designed to accommodate rapidly developing tech-
nologies, which, to be fair, is probably a greater
challenge for CBER than CDER. These ‘Points to
Consider’ are almost completely outside the ICH
process, and have been very well received by the
regulated industries.
FDA has also been keeping its eye on the public.
Advisory committee hearings are typically held
by the reviewing divisions prior to any significant
NDA approval. These hearings are open to the pub-
lic, and specifically include an agenda item that
provides for public commentary, quite apart from
the dialog that goes on between FDA staff, their
recruited outside experts and the NDA sponsor
(again, all in public). FDA has also begun to publish
its policy statements. The AIDS community, in
particular, hasbeenespecially effectiveindeflecting
FDA from its otherwise default-mode course in the
review of investigational and new drugs.
31.8 Influences on FDA activities
The FDA, like any other branch of the US govern-
ment, is subject to the oversight of Congress. It is
Congress that writes the laws that FDA must imple-
ment as regulations. FDA must understand the
Congressional intent in any law, or will find itself
called before them to justify their actions. FDA is
also dependent upon Congress for its budget,
which it must get approved yearly. The court of
public opinion has had more of an influence on the
FDA in the past 20 years than any other time in its
history. This influence is directly focused at the
FDA, or indirectly through interaction with Con-
gress or the media. The AIDS community brokethe
ground in this arena in the 1980s when they
demanded access to more drugs for this dreadful
disease more quickly. Fueled by the success of their
actions, other patient groups have challenged FDA
authority since then. Groups such as the American
Association of Retired People have voiced their
concern on a wide range of activities. The
American Academy of Pediatrics continues to
fight for more drugs for children. A number of
cancer patient groups seek the ear of the FDA on
a regular basis. Pharmaceutical trade associations
are also active voices.
Other recent regulatory developments, which
are covered elsewhere in this book, include legisla-
tion regarding risk management as a forthcoming
integral part of all NDA approvals (see also below),
and new requirements for studying potential cardi-
otoxicity (which is the subject of a valuable ICH
guidance).
Although the special nature of children in clin-
ical trials is dealt with elsewhere in this book, it
should not be forgotten that the FDA has been
influenced to make regulatory changes specific to
this age group as well. The victims of the sulfani-
lamide elixir tragedy that drove the 1938 Food,
Drug and Cosmetic Act were mostly children.
The Food and Drug Modernization Act (1997)
again explicitly encouraged IND sponsors to study
children earlier in their development programs than
had been the case previously. A six-month exten-
sion of product exclusivity upon NDA approval
was the incentive, and pediatric research guidelines
were issued (see http://www.fda.gov/ cder/pedia-
tric). In 1998, a mandatory rule requiring studies in
children for certain therapeutic areas was intro-
duced, and in 2002 the Best Pharmaceuticals for
Children Act renewed these provisions as a matter
of law, and expanded them on certain pharmacov-
igilance technical matters. The Pediatrics Research
Equity Act (2003) constituted a separate Pediatric
Advisory Committee within the FDA, and further
codified the requirements for studies in children
for almost all new molecular entities. European
regulators have done likewise in 2005.
All these regulatory innovations have improved
labeling for clinicians using drugs for children,
and have increased the frequency of pediatric clin-
ical trials manyfold. By January 1, 2006, some
720 pediatric clinical trials had been specifically
requested by FDA in connexion with new product
approvals, and of these 35% have been for efficacy
and safety, 29% for pharmacokinetics and safety,
15% solely for safety, 9% for PK–PD assessments
and 12% for various others. These trials were
reckoned to be in children with 117 different
diseases, distributed among 15 specific therapeutic
areas.
31.8 INFLUENCES ON FDA ACTIVITIES 405