A ‘more useful’ drug label: FDA seeks to add immunogenicity section to biologic labels
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Although immune-based therapies have penetrated many medical specialties, including rheumatology, some experts have expressed concerns about the labeling of these approaches, particularly regarding immunogenicity.
In response, the FDA in February published a draft guidance for industry on the topic of immunogenicity information in drug labeling. The paper covers therapeutic approaches that have the capacity to trigger an immune response and/or immunologically related adverse events. The aim is to paint a clearer picture of efficacy and safety parameters, and more clearly delineate expected immunological activity from unexpected consequences.
The guidance covers a broad cross-section of drugs, such as therapeutic protein products like monoclonal antibodies and enzymes, as well as products that have immunogenicity assessments, such as peptides, oligonucleotides and low molecular weight heparins.
Members of the public can submit comments to the FDA on the proposed guidance by April 5.
The draft comes in response to what many experts saw as a knowledge gap surrounding these drugs. In a paper published in Therapeutic Innovation & Regulatory Science in 2020, Guinn and colleagues suggested that “current U.S. Food and Drug Administration (FDA) guidance does not provide comprehensive recommendations on the communication of clinical impact of immunogenicity in labeling.”
The researchers created a database of 71 therapeutic biologics and drug products that were assessed for immunogenicity as part of the FDA approval process. Results showed that for 98% of these products, immunogenicity information was listed in the adverse reactions section of the label. Meanwhile, immunogenicity impact on pharmacokinetics was reported in 52% of drug labels, usually within the section on adverse reactions. However, supportive pharmacokinetic data did not commonly appear in the section dedicated to clinical pharmacology.
“There is inconsistency in providing supportive [pharmacokinetic] data and high variability in reporting immunogenicity impact on safety and effectiveness in labeling,” the researchers concluded. “Development of a communication framework that allows for consistent inclusion of immunogenicity impact statements in labeling could improve how immunogenicity risk is conveyed in prescription drug labeling.”
With the new draft guidance, the FDA took a key step to meet this need.
Healio Rheumatology sat down with Don Miller, PharmD, a member of the American College of Rheumatology’s Government Affairs Committee, to discuss the particulars and parameters of the guidance and what it may mean for the practicing rheumatologist.
Healio Rheumatology: Could you summarize what you see as the key points of this draft guidance?
Miller: This draft FDA guidance would reorganize drug labels for biologics and create an immunogenicity section that will incorporate relevant immunologic data for all biologic medications, including biosimilars. Instead of finding immunogenicity information under adverse effects, it would now be found under clinical pharmacology. The focus is on anti-drug antibodies primarily but can include other immunologic data. This is important because anti-drug antibodies do not necessarily cause adverse effects. There may be no adverse effects at all, or there may be changes in pharmacokinetics only.
Providing this information allows for a better understanding of the drug reaction by providers without immunology backgrounds. Therefore, the new labeling should clearer and more useful for clinicians.
Healio Rheumatology: Is this draft guidance likely to increase safety of drug prescribing?
Miller: The draft guidance could indirectly increase the safety of drug prescribing by making the impact of a drug’s immunogenicity and anti-drug antibodies clearer, particularly if there are impacts from anti-drug antibodies. Providers can better monitor for adverse effects if they are known.
Healio Rheumatology: Is this level of transparency in drug labeling a good thing, or are there drawbacks?
Miller: Any data is good data when providers are considering the appropriate treatments for their patients. As we have seen in so many other instances, context is so important when patients read these data points. Although we appreciate and encourage transparency in drug trial data, providers will be put in the position to provide explanations on what these data mean. Providers outside the specialty who use the particular medication may find it difficult to discuss risks and benefits adequately.
Healio Rheumatology: Are there concerns about how patients may view this guidance and the labeling information on immunogenicity?
Miller: Because the data are more granular, context will need to be provided to those who like to get into the details, but I do not have any concerns. More information is always better for providers to have when it comes to discussing risks, benefits and possible monitoring needs with patients.
Healio Rheumatology: Is this guidance likely to improve patient care in the rheumatology space?
Miller: Similar to your previous question, there should be some improvement to patient care by making immunogenicity information easier to find and clearer to apply in clinical practice.
Healio Rheumatology: The guidance applies to several drug classes: Monoclonal antibodies, enzymes, biosimilars, peptides, oligonucleotides, LMWH, etc. Would this guidance will impact each class differently?
Miller: The impact should be similar across drug classes.
Healio Rheumatology: Is it likely to impact prescribing habits for one class over another?
Miller: I don’t believe it will.
References:
Guinn D, et al Ther Innov Regul Sci. 2020;doi:10.1007/s43441-020-00161-z.
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