The 52 comments the FDA received during the public commentary period on the agency’s January 2017 draft guidance, Considerations in Demonstrating Interchangeability With a Reference Product, included statements from physicians concerned about the proposed policy.
The physicians represented organizations including the Coalition of State Rheumatology Organizations (CSRO), the American Society of Clinical Oncology (ASCO), the American Gastroenterological Association (AGA), the American Academy of Dermatology Association (AADA), and the American Autoimmune Related Diseases Association (AARDA), who widely prescribe biologic drugs to their patients.
Physician concerns included the extrapolation of indications, switching, labeling, naming, postmarketing studies, and the agency’s engagement of disease experts when interchangeable products are reviewed for approval.
- Extrapolation. Physicians are particularly concerned about the practice of extrapolation, in which information and conclusions from studies in one or more groups of patients is extended to make inferences for another subgroup or population of patients. Concerns included the pathophysiology of the drug as well as pediatric indications. Some comments raised the possibility of inappropriate substitution in cases where an interchangeable drug does not gain approval for all indications of the originator drug. The AGA commented that extrapolation of data should not be allowed for any indication in which the pathophysiology is known to be different or is yet to be elucidated, and noted that no data are currently available on the safety and efficacy of biosimilars approved by the FDA in US patients with inflammatory bowel disease, though some studies have been undertaken in other countries.
- Switching. Physicians in the CSRO and other groups supported the FDA’s proposed requirement that only US-licensed drugs be used in switching studies, and for switching studies to have robust designs. However, all physicians’ comments expressed concerns about the potential for switching to have a detrimental impact on patient safety. The AADA stated that forced nonmedical switching of some stable patients could result in the worsening of disease, severe flares, therapeutic failure, antibody development, and the risk for more adverse events than those associated with current therapy. The AARDA questioned whether any biosimilar could be interchangeable, particularly for patients with autoimmune diseases, which are inherently complex. ASCO strongly disagrees with potential substitution of products without the intervention or knowledge of the prescribing healthcare provider, saying that “Physicians and patients should have the ability to select evidence-based treatment options—including the specific biologic product—most appropriate for the patient’s circumstances,” and that physicians should have the authority to designate use of a biologic with “Dispense as Written” instructions. Another concern raised by clinicians was the provider’s power to prevent switching when a patient’s safety and health are at risk, as well as physician notification of switching.
- Naming and labeling. Clinicians’ comments included requests for labeling to include distinct names, statements about interchangeability, and data from clinical trials. In addition, commenters requested guidance for pharmacists to prevent the inadvertent substitution of a noninterchangeable biosimilar. For example, the AARDA said that the product label should clearly indicate which indications are—and are not—interchangeable, as this information is essential to patient safety and well-being.
- Postmarketing studies. Physicians requested real-world data on biosimilars and interchangeable products collected through postmarketing observational studies to ensure long-term safety and efficacy for all patient populations treated with biosimilars.
- Use of disease expertise. The AGA suggested that the FDA engage appropriate disease expertise when reviewing interchangeable product approvals.