30 months elapsed between NDA submission and
approval, but the patent term restoration was only
nine months; no new clinical trials or toxicology
studies were needed during this review.
The generic scandal of the 1980s involved phar-
maceutical companies making, and FDA staff
accepting, bribes in the interests of rapid generic
drug approval. No new legislation resulted, even
though two Vice-presidential commissions (one
Republican, the other Democratic) inquired into
the matter. Similarly, there was no new legislation
following the massive Clinton initiative; drug pri-
cing was probably the principal missed target on
that occasion. It is arguable whether or not these
vents triggeredthe subsequentspate ofmergers and
acquisitions within the pharmaceutical industry.
The Prescription Drug Users Fee Act (PDUFA,
1992) traded off fees paid upon NDA submission
for performance standards on the part of FDA. This
was the first time that any effective accountability
had been applied to FDA, somewhat reversing the
orientation of the Agency. PDUFA is due for
reauthorization in 2002, and an analysis ofits effect
is being conducted by several industry and govern-
ment organizations.
The last major revision of Food and Drug Law
took place in 1997, coincident with the first
reauthorization of PDUFA. The Food and Drug
Administration Modernization Act (FDAMA) of
1997 was only the third major overhaul of the
original 1906 Act. It was the first to occur without
the impetus of a disaster or perceived disaster.
After a troubled start in 1996, FDAMA received
overwhelmingly positive support in both houses of
the US Congress, getting 98 of 100 votes in the
Senate, and a unanimous vote in the House.
The perceived need for FDAMA by Congress,
the industry and ultimately the FDAwas the recog-
nition that while the law and the regulations had
changed little from the 1962 Amendments, the
requirements made by the FDA of the industry
had increased dramatically. Part was due to
advances in technology and medicine, but part
was due to FDA reviewer preferences. Both of
these contributed to the phenomenon known as
‘regulatory creep’ that was demonstrated by wide
variances across the FDA in requirements.
Although there were some significant break-
throughs that advanced healthcare and the regula-
tory process, a major portion of the legislation
focused on the formalization of ‘best practices’
that existed within the FDA and making these the
standard throughout the FDA.
Some of the major breakthroughs of FDAMA
includedformalization of the evidence needed from phar-
macoeconomic studies;authorized and regulated the dissemination of
information on unapproved uses of approved
products to healthcare providers by pharmaceu-
tical companies;enhanced theavailability of labeling information
for use in pediatric patients by recognizing the
difficulties of developing drugs for this group
and providing an incentive to undertake this
work.Examples of modernization which were the result
of identifying ‘best practices’ within FDA and
making them the standard includeimproving access to unapproved drugs;clarifying the definition of ‘substantial evidence
of efficacy’ to include only one pivotal study
provided there is adequate confirmatory evi-
dence. This had long been used for the approval
of oncology drugs, but was now able to be
applied more widely;formalization of various administrative aspects
of the IND and NDA process.Although PDUFA and FDAMA offered significant
opportunities to improve the drug development
process and make more drugs available to more
people, more quickly, for themost part, the promise
has yet to be fully realized. There are two reasons
for this, both acknowledged before the legislative
changes were initiated. The first reason is that the
‘regulatory creep’ that was being corrected was
something that took place over the period 1962–- It would be unrealistic, not to mention
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