According to Dr Lynch, the FDA’s expectations for lot selection when it comes to biosimilarity include:

• Select reference product lots sourced to a reasonable time period to capture variability
• It is expected that basis for selecting reference product lots and specific data points for inclusion in analytical similarity assessments will be provided and pre‐specified in an analytical similarity protocol
• Test reference product lots upon purchase, or stored under label conditions while still within expiry period if necessary, e.g. side‐by‐side analysis
• Select test product lots that are independent to capture lot‐to-lot variability

In addition, FDA’s expectations for lot independence include:

• What is the predominant source of attribute variability?
• For assessment of attributes intrinsic to the molecule and not affected by the drug product process, one independent drug product or drug substance should contribute only one value
  • Different drug product lots linked to the same drug substance batch(es) are not considered independent of one another
• Independent lots refer to drug product lots produced from a single drug substance batch
  • Drug product lots produced from pooled drug substance batches may mask the lot‐to‐lot variation of the constituent drug substance batches
• For attributes extrinsic to the molecule, or whose variability directly results from the drug product manufacturing process, e.g. protein content, it may be acceptable to use independently manufactured drug product lots regardless of the drug substance lot from which they were derived
• Consider need for multiple lots of other constituent materials as necessary to ensure all contributing sources of lot‐to‐lot variability are captured, e.g. more than one lot of PEG

The only problem with these requirements is that it is not always easy to gain access to samples of originator biologicals (reference products). Understanding the challenges and conducting thorough upfront planning are crucial in ensuring success [2].

Disclaimer
Dr Patrick Lynch, Product Quality Reviewer at the US Food and Drug Administration (FDA), stated that his presentation reflects the views of the author and should not be construed to represent FDA’s views or policies.

Related articles
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Ranking and evaluation of quality attributes for biosimilarity

Analytical consideration in demonstrating similarity for biosimilars

Analytical similarity for biosimilars

References
1. Lynch P. Expectations and approaches for demonstrating analytical similarity. DIA Biosimilars Conference; 24-25 October 2017; Bethesda, Maryland, USA.
2. GaBI Online - Generics and Biosimilars Initiative. Sourcing innovator products in the age of biosimilar research [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Aug 31]. Available from: www.gabionline.net/Sponsored-Articles/Sourcing-innovator-products-in-the-age-of-biosimilar-research

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