Members of the biopharmaceutical industry and pharmacists are calling for changes to the US Food and Drug Administration’s (FDA) recently released draft guidance on the Indications and Usage section of drug and biologics labeling.
Notably, the draft guidance
sets out FDA’s expectations for the content and format of the Indications and Usage section of labeling, explains the circumstances in which an indication can be broader or narrower than what was studied in the clinical trials that supported the product's approval and provides recommendations for including and placing limitations of use in the labeling.
While the Biotechnology Innovation Organization (BIO) says it supports the recommendations in guidance, especially the potential for indications to be broader than the population studied, the group calls for several changes to the guidance.
Allowing for broader indications than the population studied “is especially important for therapeutic areas in which the patient population is small, and the disease is heterogenous with highly diverse clinical manifestations, and reliable and validated endpoints that span the spectrum of the disease may not be established,” BIO writes.
BIO asks FDA to expand the guidance to include more information about surrogate endpoints used to support accelerated approval. “It would be beneficial to include information and a description to support how the surrogate endpoint ‘is reasonably likely to predict a clinical benefit,’” BIO writes, adding that such information could help physicians with limited familiarity with a novel surrogate endpoint interpret the label.
And BIO pushes back against FDA’s recommendations concerning drugs approved based on surrogate endpoints. In the guidance, FDA says that drugmakers should detail any limitations of usefulness of a drug or any uncertainty about its clinical benefits for products approved based on surrogate endpoints. BIO says it is concerned that health care providers may misinterpret such statements to mean that products granted accelerated approval have not met FDA’s standards for safety and efficacy.
“Congress and FDA have been very clear that drugs approved under accelerated approval meet the same, full statutory standards for safety and effectiveness as all other FDA approved drugs, including demonstrating substantial evidence of effectiveness,” BIO writes.
In its comments, Swiss drugmaker Novartis suggests that FDA include recommendations for including information regarding secondary endpoints “if clinically meaningful/robust data is generated” for that endpoint.
British drugmaker GlaxoSmithKline (GSK) also raises concerns about FDA’s recommendation to generally include age groups in the Indications and Usage section. “Routinely specifying age groups in the Indications section could have unintended adverse consequences such as impacting reimbursement by payors, or interfering with clinical decision-making,” GSK writes.
The American Pharmacists Association (APhA) also requests several changes to the guidance, including calling on FDA to develop a framework to standardize its approach to granting an indication that is broader or narrower than the population studied.
APhA says that FDA should test out the recommendations it makes in the guidance on the inclusion and prominence of the Limitations of Use section.
“Because prominent placement of Limitations of Use in the labeling may infer a greater risk, APhA recommends FDA test whether the labeling is confusing or misleading to health care practitioners,” APhA writes.
Additionally, APhA says it believes FDA increase its surveillance of products with expanded or narrowed indications and pay close attention to adverse events that occur in populations that were not studied and whether certain populations are being excluded from labeling more frequently than others.