The FDA today released draft guidance on the design and evaluation of comparative analytical studies that are intended to support a demonstration of biosimilarity. A previous draft guidance document on statistical approaches to evaluate analytical similarity was withdrawn in June 2018.
The FDA today released draft guidance on the design and evaluation of comparative analytical studies that are intended to support a demonstration of biosimilarity. A previous draft guidance document on statistical approaches to evaluate analytical similarity was withdrawn in June 2018.
The new guidance recognizes that analytical procedures have improved, and manufacturing science and production methods have advanced, such that there is an enhanced likelihood that a proposed product can be deemed highly similar to its reference through better targeting of the reference’s physiochemical and functional properties. For this reason, the FDA encourages the use of available state-of-the-art technology to prepare analytical studies that comprise part of a biosimilar’s application package. The FDA also encourages submission of comprehensive analytical data at the investigational new drug application stage.
The rationale for and the approach to comparative analytical assessments must be clearly described by the product’s sponsor, as this information can inform how much data will be required from animal and clinical studies. A meaningful assessment depends on the capabilities of available assays to assess features like a protein’s molecular weight, complexity, degree of heterogeneity, functional properties, impurities, and degradation. Identification of product-related variants, like storage conditions that lead to aggregation, should be included in analytical characterization.
The 3-dimensional conformation of the protein, which can be difficult to define precisely, is key; any differences should be evaluated in terms of potential effect on function and stability.
Evaluation of multiple lots is encouraged for the estimation of product variability, and the agency encourages sponsors to consult with the FDA to ensure that they select an appropriate number of lots.
In assessing differences between products, emphasis should be placed on orthogonal quantitative methods to definitively identify any differences in product attributes, and it may be useful, says the agency, to compare differences in quality attributes using a meaningful analysis algorithm.
Factors to consider when performing the comparative analytical assessment include the following:
The guidance highlights the fact that a full characterization of the reference, and consideration of publicly available information, will form the basis of understanding the reference, and lot-to-lot variability will be inherent to the reference. Sponsors should acquire multiple product lots of the reference and should include 6 to 10 lots in their assessments. Ideally, these lots will be derived from different drug substance batches to capture variability. Sponsors should be prepared to account for all lots acquired and characterized.
When sponsors use non—US-licensed comparators, they should provide comparative analytical data and analyses for all pairwise comparisons. Combining data from US and ex-US references would not be acceptable.
Sponsors should develop comparative analytical assessment plans and discuss their approaches with the FDA as soon as possible in the development process. The agency recommends that sponsors develop a risk assessment tool to rank the reference’s quality attributes in terms of potential impact on mechanism of action and function.
Appropriate analyses of comparative analytical data are also necessary, and factors that should be considered when determining how to evaluate data include:
The FDA will evaluate the totality of the analytical data, and results of a given assay that do not meet prespecified criterial are not, on their own, preclusive of a demonstration of high similarity, the guidance points out.
Exploring the Biosimilar Horizon: Julie Reed's Predictions for 2024
February 18th 2024On this episode of Not So Different, Julie Reed, executive director of the Biosimilars Forum, returns to discuss her predictions for the biosimilar industry for 2024 and beyond as well as the impact that the Forum's 4 new members will have on the organization's mission.
BioRationality: MHRA's Procedure Enables Automatic Registration of Biosimilars Approved Elsewhere
March 18th 2024Sarfaraz K. Niazi, PhD, explains how the new international recognition procedure under the Medicines and Healthcare Products Regulatory Agency (MHRA) could expand biosimilar access within the United Kingdom, in his latest column.
A New Chapter: How 2023 Will Shape the US Biosimilar Space for 2024 and Beyond
December 31st 2023On this episode of Not So Different, Cencora's Brian Biehn and Corey Ford take a look back at major policy and regulatory advancements in 2023 and how these changes will alter the space going forward.
Coherus Biosciences Cites Biosimilars as Main Drivers of 2023 Revenue Growth
March 14th 2024In its earnings report for the fourth quarter and full year of 2023, Coherus Biosciences detailed its rising revenue growth, which it partly attributed to increased sales for its pegfilgrastim and ranibizumab biosimilars.
Filgrastim Biosimilars in Europe: 15 Years of Real-World Evidence for Zarxio
March 13th 2024A review looking back at the last 15 years of experience with the first filgrastim biosimilar (Zarxio) provides a detailed overview on how filgrastim biosimilars came to be and the evidence behind why oncologists have come to accept them as standard practice.