Regulatory Update, February 2016
Monday, February 1, 2016
Draft FDA Guidance on Safety Assessment for IND Safety Reporting
In the Dec. 17, 2015, edition of the Federal Register, the FDA announced the availability of a draft guidance document titled Safety Assessment for IND Safety Reporting. The draft guidance provides recommendations to sponsors on developing a systematic approach to investigational new drug application (IND) safety reporting for human drugs and biological products developed under an IND. The draft guidance is a follow-on to the 2010 guidance for industry and investigators titled Safety Reporting Requirements for INDs and BA/BE Studies that provides recommendations for how sponsors of INDs can identify and evaluate important safety information that must be submitted to the FDA and all participating investigators, including a recommendation that sponsors develop a safety assessment committee.
There are recommendations on the following: the composition and role of a safety assessment committee; aggregate analyses for comparison of adverse event rates across treatment groups; planned un-blinding of safety data; reporting thresholds for IND safety reporting; and the development of a safety surveillance plan.
It is critical for sponsors to detect and report, as early as possible, serious and unexpected suspected adverse reactions (SUSAR) and clinically important increased rates of previously recognized serious adverse reactions. Early detection of such occurrences will enable sponsors to carry out their obligation to monitor the progress of the investigation and, when necessary, to take steps to protect subjects to allow an investigational drug to be safely developed despite potential risks. Early detection also allows sponsors to report meaningful safety information to the FDA and all participating investigators in an IND safety report as soon as possible.
Timely reporting of meaningful safety information allows the FDA to consider whether any changes in study conduct should be made beyond those initiated by the sponsor and allows investigators to make any needed changes to protect subjects. For those reasons, the draft guidance provides recommendations intended to help sponsors meet their reporting obligations. The FDA recommends that sponsors develop a safety assessment committee and a safety surveillance plan as key elements of a systematic approach to safety surveillance. A safety assessment committee would be a group of individuals chosen by the sponsor to review safety information in a development program and tasked with making a recommendation to the sponsor regarding whether the safety information must be reported in an IND safety report. A safety surveillance plan should describe processes and procedures for assessing serious adverse events and other important safety information.
Submit electronic or written comments by Feb. 16 to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852. The notice includes detailed instructions on how to submit written comments with confidential information, if applicable; the instructions should be followed carefully. Identify comments with Docket No. FDA-2015-D-4562.
Final FDA Guidance on Studies of Implantable Minimally Invasive Glaucoma Surgical Devices
In the Dec. 15, 2015, edition of the Federal Register, the FDA announced the availability of a final guidance document titled Premarket Studies of Implantable Minimally Invasive Glaucoma Surgical (MIGS) Devices. This leapfrog guidance document was developed to notify manufacturers of the recommended nonclinical and clinical studies to support a premarket approval application (PMA) for implantable MIGS devices.
The guidance document recommends non-clinical and clinical studies to support a PMA for implantable MIGS devices. Current surgical treatments are aimed at reducing intraocular pressure and often reserved for moderate to severe disease. During the past decade, novel medical tools called “MIGS devices” have emerged. They are designed to treat less severe glaucoma by enhancing physiological aqueous outflow with an approach that causes minimal ocular trauma.
This document makes final the draft version of the guidance. The FDA received 12 sets of public comments and revised the guidance, where applicable. Multiple comments were received regarding the definition of glaucoma and the inclusion of pre-perimetric glaucoma. Based on discussion at the “FDA/American Glaucoma Society Workshop on Supporting Innovation for Safe and Effective Minimally Invasive Glaucoma Surgery,” Feb. 26, 2014, the FDA does not believe that pre-perimetric glaucoma (i.e., optical coherence tomography changes and optic nerve changes without any field abnormalities) should be included in those interventional studies because there are differing opinions among experts about whether this condition warrants surgical treatment. The guidance is a “leapfrog” guidance; leapfrog documents are intended to serve as a mechanism by which the FDA can share initial thoughts regarding the content of premarket submissions for emerging technologies and new clinical applications that are likely to be of public health importance very early in product development, generally before the FDA has even received any such submissions. It represents the FDA’s initial thinking and the recommendations may change as more information becomes available. The current recommendations are designed to provide a conservative approach to protection of human subjects.
Submit electronic or written comments as instructed above and identify them with Docket No. FDA-2015-D-0288.
The Regulatory Update is excerpted from Research Practitioner, Volume 17, Number 1, January-February 2016.