The US Food and Drug Administration has proposed allocating an extra US$4.6 million a year to improving and expediting new drug development as part of a package of measures that would increase the annual user fees levied on industry by US$87.4 million (+29%) to US$392.8 million.

The fee increases are among the FDA’s recommendations to Congress for re-authorisation of the 1992 Prescription Drug User Fee Act (PDUFA). The Act has since been re-authorised twice, each time for a five-year term, with the current PDUFA III programme scheduled to end on 30 September 2007.

The FDA’s proposals for PDUFA IV, which would cover the fiscal years (FY) 2008 to 2012, were presented at a public meeting in Washington on 16 February. The agency has been working on the recommendations for more than a year, in consultation with stakeholders including Congress, industry, patient advocates, healthcare professionals and consumers.

Post-marketing needs tightening up

The bulk (US$29.3 million) of the proposed US$37.9 million increase for programme enhancements would go on tightening up the FDA’s post-marketing surveillance programme to ensure the continued safety of medicines after launch. A further US$4.6 million, to include staff costs for 20 more full-time equivalents, would be directed at expanding the implementation of Good Review Management Principles (GRMPs) within the agency and providing guidance to industry on issues such as clinical trial design.

One aspect of the GRMP initiative would be giving applicants for marketing approval a better idea of review timelines, including the expected date for starting discussions on product labelling and for any FDA requests relating to post-marketing studies. Historically, labelling discussions have begun in the late stages of review, often in the last week before approval, the agency notes. Similarly, it often makes requests for post-marketing commitments late in the review cycle.

In terms of expediting new drug development, the FDA intends to put out draft guidance documents for industry on clinical hepatotoxicity, non-inferiority trials, adaptive trial designs and end of Phase II (a) meetings by the close of FY 2008. Draft guidance on multiple endpoints in clinical trials, enriched trial designs and imaging standards for use as an endpoint in clinical trials should be out be the end of FY 2009, FY 2010 and FY 2011 respectively.

Additional staff resources would also free up reviewer time to participate in “scientific research collaborations that will ultimately help clarify regulatory pathways for new technologies and potential new biomarkers for drug safety and effectiveness," the FDA said. This would include workshops geared to guidance development in the fields of predictive toxicology, biomarker qualification, missing trial data and new approaches to a structured model for benefit/risk assessment.

The final proposals for the PDUFA IV programme will be forwarded to Congress once the FDA has weighed up all the public comments on its recommendations and made any necessary adjustments. Many of the goals cited overlap with those of the FDA’s Critical Path initiative, launched in March 2004 with the aim of modernising and streamlining medical product development. By Peter Mansell