FDA defends guidance timekeeping but admits one document took 15 years
The Agency revealed it takes the Center for Drug Evaluation and Research (CDER) an average of 710 days to finalise draft guidance, and the Center for Biologics Evaluation and Research (CBER) 743 days. Medical device guidance is finalised, on average, after 797 days. All other FDA Centers were much quicker to finalise guidance on products like nutritional supplements and tobacco.
A document on deciding the “sameness” of monoclonal antibodies with orphan drug designations took the longest to finalise, at almost 15 years, but the FDA claimed this is an exception, as the Agency had forgotten about the guidance during reorganisation and staff changes at CDER.
Senators: ‘Significant concern’
The FDA defended its timekeeping in a letter last week responding to Republican senators. Lamar Alexander (R-TN) and three colleagues wrote to Margaret Hamburg in May 2014, saying the FDA does not finalise guidance in a timely manner. They also expressed “significant concern about the FDA’s use of draft guidances to make substantive policy changes.”
Industry insiders claim draft guidances are “increasingly becoming default FDA policy,” said the politicians.
Although official policy says guidance documents are distributed for comment purposes and are not binding, in the absence of finalised guidance, “draft guidances are increasingly becoming default FDA policy and position,” said Alexander’s letter.
It also claimed the FDA website does not differentiate between draft and final guidances, making them seem to have equal weight.
‘Draft’ guidance: binding?
Thomas Kraus, Associate Commissioner for Legislation, FDA, responded, saying guidance documents are generally not legally enforceable and do not bind manufacturers or the FDA to a course of action. Instead, they represent “the FDA’s current thinking.
“Therefore, FDA employees may depart from guidance documents only with appropriate justification and supervisory concurrence. Because guidance is not binding, affected parties may choose to use an approach other than the one set forth in a guidance document, unless the guidance document is reiterating legal mandates.”
Kraus added that documents are clearly marked to indicate whether they are drafts or final versions.
Delays
Kraus said delays writing and finalising documents are inevitable, since they need input from subject matter experts, sometimes involving the Department of Health and Human Services or the Office of Information and Regulatory Affairs. Once a draft guidance is issued and the public comment period is closed, the document needs another round of review from medical, scientific or technical experts.
The FDA is looking for ways to finalise draft guidances more quickly, Kraus said, but warned the Agency needs more funds:
“Without new resources, in order to ensure that guidances can be finalised in a timely manner, FDA will need to issue fewer discretionary guidance documents.
“This may disappoint stakeholders, as they often tell us that they find draft guidances provide useful information, even before they are finalized.
“In light of this concern, the Agency may modify actions and target dates based on stakeholder feedback.”
Kraus added the FDA is working to improve transparency. FDA guidances are not currently all located in one place online. Since 2011 the Agency has been building a centralised website that links to each Office’s list of guidances, but Kraus said this is an enormous IT task and “given the number of existing guidances, revising the already entered metadata will take time.” He did not give an expected completion date.
