FDA Regulation of Biologics

Nexcelom image cytometry supports each step in the FDA process

Complete FDA guidance, compliance, and regulatory information on biologics is available at: https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics

Clonality assurance is a crucial part of the overall control strategy to ensure biologic safety, stability, quality, and efficacy.

Regulatory guidelines require the assurance of monoclonality before generating a master cell bank (MCB), and when such evidence is not available, additional studies are typically required to further ensure consistent long-term manufacturing of the product.

The FDA has identified clonality as one of the most crucial steps in guaranteeing quality and safety. The FDA recommends performing two rounds of limiting dilution or fluorescent-activated cell sorting along with imaging to supplement clonality data. These verification steps greatly increase the probability of monoclonality. The World Health Organization Expert Committee on Biological Standardization stated that cloning procedures should be fully documented with appropriate statistics and detailed images [WHO, 2013, 2016].

FDA reviewers assess MCB clonality during the Investigational New Drug application stage, including information on:

  • Cloning processes
  • Clone expansion
  • Clone selection
  • Clone testing in accordance with ICH, Q5D, and EMA/CHMP

Clonality assurance must be submitted along with the Biologics License Application.

ISO Cell Counting Standards

The FDA has been implementing a new regulatory framework as mandated by the 21st Century Cures Act. In 2014, the FDA and the National Institute of Standards and Technology (NIST) held a workshop to share practices in cell counting measurements. Stemming from the workshop came the publication of two ISO Cell Counting Standards Part 1 and Part 2 [ISO 2018a; ISO 2018b]. Nexcelom Bioscience has been a major contributor to the creation of these standards, providing guidance and advice on practical usage of the documents to researchers and scientists. For more information, please visit our website: