EMA revises Guidance on Development, Production, Characterization and Specification for Monoclonal Antibodies and related Products.

In July, the EMA announced the 2nd revision of its guidance document on "Quality of Monoclonal Antibodies and Related Products".


This 2016 guideline is also being revised due to the revision of the related guideline "Radiopharmaceuticals based on monoclonal antibodies" (3AQ21A), because when it became effective, it replaced both the guideline on "Production and quality control of monoclonal antibodies" (3AB4A) and the quality requirements for monoclonal antibodies previously listed in the guideline "Radiopharmaceuticals based on monoclonal antibodies" (3AQ21A).

Current Revision - The Concept Paper

However, the current guideline for monoclonal antibody-based radiopharmaceuticals (Eudralex 3AQ21A) was last revised in 1991, necessitating a thorough revision because it no longer reflects the current state of science and technology. Accordingly, the EMA defined the problem as follows:

"Since 1991, numerous developments have been made in the field of radiopharmaceuticals, i.a. various new antibody formats, new conjugation technologies. At the same time, new manufacturing technologies and analytical methods have evolved concomitant with new regulatory expectations, which are partially reflected in current regulatory documents. These developments need to be addressed in a revised guideline. The revision of the Guideline on Radiopharmaceuticals Based on Monoclonal Antibodies will be prepared in parallel with the revision of the quality Guideline on radiopharmaceuticals (EMEA/CHMP/QWP/306970/2007) and with the development of a clinical Guideline for the development of therapeutic radiopharmaceuticals. This specific document will not address the same areas, but complement the links between quality, non-clinical and clinical modules to be included in the dossier."

The revision is intended to reflect current developments in both radiopharmaceuticals and monoclonal antibodies. It is intended to provide recommendations on quality and non-clinical aspects of these products. It will also touch on broader issues or need to address subsequent issues that have come up from the work to date and feedback in the relevant drafting group:

  • A clear terminology to identify starting materials, intermediates, linkers, active ingredients and final products
  • Structure of the CTD quality and non-clinical modules for intermediates, active substance and final product
  • Reference to the dossier of an already approved medicinal product (e.g., monoclonal antibodies, radionuclide intermediates) and application of an ASMF procedure for radiopharmaceutical precursors
  • Specification requirements for radionuclides, e.g., radionuclide characteristics, radionuclide concentration, radionuclide purity, radiochemical purity, specific activity, chemical composition, chemical impurities, chemical stability
  • Requirements and description of prior state of art radiolabeling method (to produce a stable conjugate) (either performed by the manufacturer or by the user)
  • Specification requirements for active ingredient and finished product, e.g., identity, purity, potency, sterility
  • Shelf-life assignment, labeling, and packaging of the finished product
  • Non-clinical testing, e.g., mechanism of action, stability of conjugate in plasma, free radionuclide, free antibody, reproductive function, fetal toxicity, mutagenic potential, carcinogenic potential
  • Guidelines for calculating absorbed dose for target tissues/organs, e.g., milliGray per unit of administered activity, taking into account decay rates

Public comment of the Concept Paper  was open until October 31, 2023. More detailed information can be found on the EMA website at.
"Development, production, characterisation and specifications for monoclonal antibodies and related products".

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