Industry Seeks More Leniency in FDA Draft Guidance on Safety Assessments for INDs

Regulatory NewsRegulatory News
| 17 February 2016 | By Zachary Brennan 

A number of drugmakers are calling on the US Food and Drug Administration (FDA) to be more flexible with sponsors in developing guidance on safety assessments for investigational new drug (IND) applications, according to comments published Wednesday on the draft document.

The draft guidance from December calls on sponsors to create a safety assessment committee (SAC) to review safety information in a clinical development program and make recommendations to the sponsor on whether a numerical imbalance in the unblinded rates of safety events meets the criteria for IND safety reporting.

FDA says a SAC “should regularly perform unblinded comparisons of rates across treatment groups for serious adverse events that are prespecified in the premarket safety surveillance plan as anticipated serious adverse events or as previously recognized serious adverse reactions listed in the protocol or the investigator brochure, as long as appropriate steps to maintain the overall study blinding are taken.”


Industry group BIO called on FDA to revise the draft guidance to allow more flexibility for sponsors to accommodate product-specific aspects of a development program, given companies’ pre-existing internal safety monitoring processes and governance.

“As currently written, the draft guidance’s recommendations regarding the SAC, would present significant operational challenges, especially for small- and mid-sized companies,” BIO said. “We also note that it is unclear whether the presence of an SAC will result in earlier detection of important safety information. As such, we believe it would be more beneficial and appropriate if this draft guidance focused on safety surveillance plans, which in some cases may include an SAC as part of the plan.”

Similarly, GlaxoSmithKline said in its comments that it believes there are several viable options to achieve the desired goal of proactively identifying emerging signals based on aggregate safety review.

“This may include the constitution of an external SAC or enhancement of the responsibilities of existing safety review committees. To that end, GSK recommends that the agency allow for a flexible approach to meet the regulatory requirements, the details of which would be clearly articulated in the Safety Surveillance Plan (SSP). Such an approach will allow sponsors to take into consideration a variety of factors in determining the best approach to review aggregate safety data from ongoing trials,” GSK said.

Generic drugmaker Teva also noted that the roles of many industry internal safety monitoring teams overlap with the roles of the SAC described in the draft guidance. The company said the addition of an independent team to look at unblinded data routinely “will require extensive additional human resource, logistical, and operational support. Furthermore, time will be required to develop procedures, train, and ensure all resources are adequately ready to implement. As such, Teva proposes strengthening the role of the current internal safety monitoring structure with blinded monitoring and only utilize unblinding when an imbalance with a comparator occurs, without adding a SAC.”

Perhaps a pilot program with 3-4 pharmaceutical companies of various sizes with two to three drugs per company would be useful to more fully appreciate the practicalities of implementing the agency’s proposal, Teva added.

The Israel-based company also called on FDA to consider a more aligned approach with the European Medicines Agency as harmonization of safety requirements provides the opportunity to optimize the ability for manufacturers and regulatory agencies to gain efficiencies in global safety reviews.

In addition, Merck said the draft guidance is “too prescriptive regarding the composition and role of the proposed SAC…It would be resource-intensive and duplicative to develop parallel SACs with the same cross-functional expertise to review unblinded data from ongoing clinical studies if an appropriate, dedicated cross‐functional team is already in place.”

Docket Folder of 14 Comments on IND Safety Reporting Draft Guidance


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