FDA Issues Several Draft Guidance Documents

Since the last issue, FDA released six draft guidance documents in the Federal Register. Interested persons should submit electronic or written comments on draft FDA guidance documents by the date specified (in parentheses) to have their comments considered for preparation of the final document, but comments will be accepted at any time and may be used in the future. Submit comments as instructed above. Identify comments with the associated Docket number (also in parentheses).

Clinical Evaluation of Drugs for Treatment of Gastroparesis

On July 23, 2015, FDA announced a draft guidance titled “Gastroparesis: Clinical Evaluation of Drugs for Treatment.” This draft guidance is intended to provide sponsors with FDA’s current thinking regarding clinical trial design and clinical endpoint assessments to support development of drugs for treatment of diabetic and idiopathic gastroparesis. (Docket No. FDA-2015-D-2479; September 21, 2015)

Common Issues in Drug Development of Rare Diseases

On August 17, 2015, FDA announced a draft guidance titled “Rare Diseases: Common Issues in Drug Development.” The purpose of this draft guidance is to advance and facilitate the development of drugs and biologics to treat rare diseases. Drug development for rare diseases has many challenges related to the nature of these diseases. This draft guidance is intended to assist sponsors of drug and biological products for treating rare diseases in conducting more efficient and successful development programs through a discussion of selected issues commonly encountered in rare disease drug development.

Although these issues are encountered in other drug development programs, they are frequently more difficult to address in the context of a rare disease than a common disease for which there is more widespread medical experience. These issues are also more acute with increasing rarity of the disorder. (Docket No. FDA-2015-D-2818; October 16, 2015)

Biomarker—Plasma Fibrinogen in Studies Examining COPD

On July 7, 2015, FDA announced a draft guidance titled “Qualification of Biomarker—Plasma Fibrinogen in Studies Examining Exacerbations and/or All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease.” This draft guidance provides a qualified context of use (COU) for plasma fibrinogen in interventional clinical trials of chronic obstructive pulmonary disease (COPD) subjects at high risk for exacerbations and/or all-cause mortality. This draft also describes the experimental conditions and constraints for which this biomarker is qualified through FDA’s Biomarker Qualification Program. This biomarker can be used by drug developers for the qualified COU in submissions of INDs and other applications without the relevant FDA review group reconsidering and reconfirming the suitability of the biomarker.

This draft guidance provides qualification recommendations for the use of plasma fibrinogen, measured at baseline, as a prognostic biomarker to enrich clinical trial populations of COPD subjects at high risk for exacerbations and/or all-cause mortality for inclusion in interventional clinical trials. This biomarker should be considered with other subject demographic and clinical characteristics, including a prior history of COPD exacerbations, as an enrichment factor in these trials. FDA concluded that analytically valid measurements of the biomarker can be relied on to have a specific use and interpretable meaning. (Docket No. FDA-2015-D-2244; September 8, 2015)

Biomarker—Total Kidney Volume in Studies for Treating ADPKD

On August 17, 2015, FDA announced a draft guidance titled “Qualification of Biomarker—Total Kidney Volume in Studies for Treatment of Autosomal Dominant Polycystic Kidney Disease.” This draft guidance provides a qualified COU for total kidney volume (TKV), measured at baseline, to be used as a prognostic enrichment biomarker to select patients with autosomal dominant polycystic kidney disease (ADPKD) at high risk for a “progressive decline” in renal function, defined as a confirmed 30% decline in the patient’s estimated glomerular filtration rate (eGFR), for inclusion in interventional clinical trials. This biomarker may be used in combination with the patient’s age and baseline eGFR as an enrichment factor in these interventional clinical trials. (Docket No. FDA-2015-D-2843; October 16, 2015)

Qualification of Testicular Toxicity: Evaluation during Drug Development

On July 17, 2015, FDA announced a draft guidance titled “Testicular Toxicity: Evaluation during Drug Development.” This draft guidance is intended to help sponsors identify nonclinical signals that raise concern regarding the potential for human testicular toxicity and to evaluate those signals appropriately in human studies. The draft guidance describes the standard battery of nonclinical studies that are used to assess the effects of pharmaceuticals on the male reproductive system. It discusses findings in nonclinical studies that may increase the level of concern for drug-related testicular toxicity. Examples of nonclinical studies that could be used to further evaluate initial signals of testicular toxicity are also described. The draft guidance then provides a general approach on how to weigh the relevance of nonclinical findings, taking into account factors that can confound the interpretation of these findings. (Docket No. FDA-2015-D-2306; October 15, 2015) 

The Regulatory Update is excerpted from Research Practitioner, Volume 16, Number 5, September-October 2015.