Safety First in Biotech Development - Heightened attention to product safety issues is slowing the approval process for new therapies. - BioPharm International


Safety First in Biotech Development
Heightened attention to product safety issues is slowing the approval process for new therapies.

BioPharm International
Volume 22, Issue 11


REMS assessments include updated information on postapproval studies or clinical trials undertaken by the sponsor, including the status of the study, expected completion date, and whether any difficulties have been encountered in meeting set goals. This information also is provided in annual reports on postapproval studies, as required by FDAAA in an effort to address complaints that pharmaceutical companies have failed to complete agreed-on postmarketing studies in a timely manner. Congress authorized the FDA to require postapproval studies to achieve specific objectives and to levy fines on companies that miss agreed-on deadlines.

Consequently, FDA reviewers now have to determine the scope and timing of postmarketing studies as part of the application review process. Instead of merely vetting study proposals from manufacturers, agency staffers have to examine what scientific data can best assess known and unknown serious risks and set appropriate timeframes for completion of postmarket studies and trials.

This greater scrutiny of postmarketing studies seems to be having a notable effect. The FDA's latest annual report on the program showed considerable progress by manufacturers in achieving "on schedule" status for fulfilling postmarketing study obligations. About 20% of studies are ongoing (started on schedule) or submitted to the FDA, while most are "pending"—that is, not yet started, but not delayed. This category includes many studies involving pediatric populations, which have to wait until all other safety information is submitted and reviewed.

FDAAA also authorizes the FDA to require additional postmarket studies for already approved drugs and to require changes in labeling when new safety information emerges. The agency sent out 14 letters requiring additional studies from mid-2008 to mid-2009, and issued 18 safety labeling notification letters during that period, another task that taps agency resources.


Woodcock hopes that CDER's 21st century review process will deal with these new challenges by better managing the application review process. The aim is to compress application review times upfront to provide more leeway at the end of the review period and address safety issues and resolve internal and external disputes. This is a considerable challenge, though, because the average NDA consists of 10 gigabytes of material, a massive amount of information for reviewers to digest.

CDER conducted a pilot program last year that reviewed 17 applications for NMEs under the system and plans to extend the streamlined approach to most NMEs and new BLAs this year and to all applications and supplements by 2012. The new process involves meeting in advance with manufacturers to identify key issues, such as whether an advisory committee meeting will be needed and potential postmarket safety requirements. There are earlier internal deadlines for establishing multi-disciplinary review teams, for identifying application deficiencies, and for reviewing product labeling to meet approval decision timeframes. These efforts may get the FDA on track with review deadlines, but changes have to support more stringent assessment of biomedical safety issues and ensure safe use throughout the product lifecycle.

Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634,

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