FDA issues draft guidance on biosimilar analytical studies

The draft guidance advises industry to minimize differences between a biosimilar and its reference biologic including in the choice of expression system and manufacturing process.

The US Food and Drug Administration (FDA) has been active in encouraging biosimilar development of late, publishing its long-awaited interchangeability guidance earlier this month. In its latest push the Agency has issued draft guidance entitled: ‘Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations Guidance for Industry.’

The document makes recommendations on the design and evaluation of analytical studies to help a developer demonstrate its candidate is a biosimilar to a reference product. It also aims to provide guidelines to show scientific and technical information for the chemistry, manufacturing, and controls (CMC) portion of a marketing application for a proposed product submitted under the dedicated 351(k) biosimilar pathway.

Among the factors the Agency tells industry it needs to consider is the choice of expression system.

“Minimizing differences between the proposed product and reference product expression systems to the extent possible can enhance the likelihood of producing a biosimilar protein product,” the guidance states.

“Possible differences between the chosen expression system (i.e., host cell and the expression construct) of the proposed product and that of the reference product should be carefully considered because the type of expression system will affect the types of process- and product-related substances, impurities, and contaminants (including potential adventitious agents) that may be present in the protein product.”

Whichever expression system a biosimilar developer chooses to use, the FDA expects that the expression construct for a proposed product will encode the same primary amino acid sequence as its reference product.

Manufacturing process

The manufacturing process itself is also a key factor highlighted by the agency, which calls for a comprehensive understanding of all steps in the manufacturing process to be established during product development.

“As a scientific matter, characterization tests, process controls, and specifications that will emerge from information gained during process development must be specific for the proposed product and manufacturing process. The use of enhanced approaches to pharmaceutical development, along with quality risk management and effective quality systems, will facilitate the consistent manufacturing of a high-quality product.”

The Agency adds that sponsors looking to make manufacturing changes after the initial analytical assessment must “demonstrate comparability between the pre- and post-change proposed product and may need to conduct additional studies.”

Industry has 60 days to comment on the draft guidelines, the full text of which can be found below.

Development of Therapeutic Protein Biosimilars by Dan Stanton on Scribd