FDA finalizes guidance for drugs and biologics containing nanomaterials

Regulatory NewsRegulatory News | 25 April 2022 |  By 

The US Food and Drug Administration (FDA) has released its final guidance for industry on human drug and biological products that contain nanomaterials.
Initial draft guidance for industry, released in December 2017, noted that FDA doesn’t distinguish between whether a drug or biologic with nanomaterials are benign or harmful, but products containing nanomaterials “may merit particular examination” regarding intrinsic and extrinsic factors to assess risks and benefits. (RELATED: Nanomaterials: FDA Issues Draft Guidance for Drugs and Biologics, Regulatory Focus 18 December 2017)
“FDA believes that a suitable framework for evaluating potential risk(s) associated with drug products containing nanomaterials should assure (1) adequate characterization of the nanomaterial, and (2) adequate understanding of a nanomaterial’s intended use and application, and of how the nanomaterial attributes relate to product quality, safety, and efficacy,” the agency wrote.
Two “noteworthy” changes were made to the final guidance from the initial draft guidance, according to a notice in the Federal Register. The first change involves adding a glossary with 26 terms to the end of the final guidance to help stakeholders understand how they are described throughout the document. FDA also updated a portion of the guidance that outlined abbreviated new drug applications (ANDAs) for products with nanomaterials “to reflect FDA’s current thinking with respect to abbreviated applications.” The final guidance’s section on over-the-counter (OTC) monograph drugs was changed as well to reflect the OTC reform provisions of the Coronavirus Aid, Relief, and Economic Security Act, the agency said.   
Comments from stakeholders
In 2018, FDA received 13 public comments from stakeholders on the draft guidance, which the agency considered when writing the final version. In general, commenters welcomed the guidance from FDA in the area of nanomaterials and nanotechnology.
Regulation around engineered nanomaterials (ENM) in pharmaceutical products “is a broad scope that tends to consider their safety/applicability as a function of their larger elemental counterparts,” the Teratology Society wrote in their comment. “This misstep considerably impairs the advancement of ENM (and related technologies) that may make tremendous contributions to human health or advance our endeavors on an unrealized scale. Hence, the need for such a document from the FDA is timely and significant.”
Researchers at the Duke University Science Regulation Lab highlighted the inconsistencies between how FDA defines nanomaterials compared with other agencies and institutions in the US and globally. “The discrepancies of characterizations between domestic agencies and inside the international community suggests opportunities for the FDA to more accurately define the relevant characteristics of nanomaterials,” they wrote.
Allergan agreed that nanomaterials are a “wide and diverse range” of potential therapeutics, active pharmaceutical ingredients (APIs) and formulations with “own critical and often unresolved scientific challenges to understand and address when developing an ANDA product.”
“Thus, while we agree with many of the provisions enunciated in the Draft Guidance and support their adoption by applicants and FDA in the development and review of applications for nanomaterial-containing products, we understand the Draft Guidance to represent a first step to resolving and answering these questions,” Allergan wrote.
Vifor Pharma asked FDA in their comment to note the challenges of having products containing nanomaterials approved under the ANDA pathway. Using the term “non-biological complex drugs” (NBCDs), Vifor argued that this product category “nano-particulate structures that cannot be isolated and fully quantitated, characterized, and/or described by physicochemical analytical means” and “cannot be adequately characterized to support a determination of sameness [and] will differ as a result of differences in manufacturing process.”
“Vifor urges FDA to acknowledge that for follow-on versions of such products, a stepwise approach, such as that used for biosimilars, should apply,” the company said. “In this way, the Agency can ensure that all follow-on drugs containing nanomaterials are safe and effective for patients.”
The International Pharmaceutical Excipients Council of the Americas (IPEC-Americas) shared similar concerns with regard to how FDA uses nanomaterial-related terminology, and how the agency defines nanomaterial dimensions relative to other US agencies and institutions as well as globally. Specifically, IPEC-Americas asked FDA to clarify how it defined “excipient” and any modifiers to the term.
“We believe that the various excipient references are confusing and could be misinterpreted that all or most excipients contain nanoparticles or were purposefully designed to be engineered nanomaterials. Realistically, only a small portion of excipients contain nanoparticles and even fewer were specifically designed as engineered nanomaterials,” they wrote.
Drug Products, Including Biological Products, that Contain Nanomaterials - Guidance for Industry
Federal Register notice


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