Back in September the US Food and Drug Administration announced that it was going to delay its publication of draft guidance on the qualification of drug development tools, originally promised for the summer.  However, this draft guidance was finally published at the end of October.  While still in draft form, the Guidance substantially expands on the outline of the pilot qualification process given in an article written by two members of the Center for Drug Evaluation and Research published in 2007.

The new guidance principally provides information on the proposed administrative process that will be followed by the FDA in order to qualify new drug development tools (DDTs).  Qualification is defined as “a conclusion that within the stated context of use, the results of assessment with a DDT can be relied upon to have a specific interpretation and application in drug development and regulatory review.”  The document discusses two forms of DDT – biomarkers and patient-reported outcome scales.  There are couple of points that bear discussion in relation to biomarkers.

Firstly, the new qualification procedure is aimed at enhancing the utility of a qualified biomarker across the industry.  Hence, while previously use of a biomarker may have been part of an NDA, IND or BLA, this new programme is designed to make public those biomarkers that satisfy the qualification process, so that future drug development programmes can take advantage of already knowing that the biomarker has been qualified for a particular purpose.  Of course, wherever a new biomarker is proprietary, it can be retained as such by not using the new qualification process, but by remaining part of the NDA, IND or BLA.  This new programme, it seems therefore, is not particularly aimed at individual companies, but more towards collaborative groups that together can share the burden of the development of the drug development tools and submission to the FDA.  Indeed, less than a month after the draft guidance was published, several major pharmaceutical companies and leading academic institutions announced such a collaborative biomarker consortium for COPD.

Secondly, while there is detailed information as to the administrative process, there is no information on the level of evidence required by the FDA to take a biomarker through from submission to qualification.  There are a number of discreet stages that have to be undertaken, but nowhere are the criteria on which a new biomarker will be assessed described.  The means by which such an assessment may be made are described:  In the first stage they include a consultation process between the submitter and the FDA, and formal assessment of the biomarker follows, to include discussion at internal FDA meetings, discipline reviews and potentially even public discussions.  However, the level of evidence required for success at each stage is not discussed.

It is tempting to suggest that this gap in the document is due primarily to the difficulty in formalising the criteria required for qualification of a biomarker.  The wide range of uses to which biomarkers may be put, whether to preselect individuals for study or treatment, inform about disease progression, predict drug efficacy or toxicity or follow dynamically treatment in an individual, makes it difficult a priori to put together criteria that will apply in all cases.  If this supposition is true, and each biomarker will be assessed on its own merits, with no reference to pre-determined criteria, the new qualification procedures do at least give the scientific community the ability to comment and provide feedback on decisions made, since all new qualifications will be published.  Indeed the guidance states “Once a DDT is qualified for specific use, the context of use may become modified or expanded over time as additional data are collected, submitted, and analyzed.  Alternatively, if the growing body of scientific evidence no longer supports the context of use, the DDT qualification may be withdrawn.”  Of concern, such scrutiny will not be applied to proprietary biomarkers submitted as part of INDs, NDAs or BLAs, but some scrutiny and sharing of validation study data is at least a move in the right direction.   The FDA’s qualification process seems likely to stimulate a further increase in the utility of biomarkers as drug discovery tools.

It should be noted that the Guidance Document is still in draft form.  Published on October 25, the FDA is asking for comments and suggestions to be submitted to them by January 24, 2011 for consideration when preparing the final document.