New USP Chapters regarding Testing for Subvisible Particles

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17-19 September 2024

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The USP has published the revised chapter on testing for subvisible particles <1788> as well as new monographs on the individual test procedures Light Obscuration (LO), Membrane Microscopy (MM) and Flow Imaging as drafts.

In contrast to the test for visible particles, the test for non-visible (subvisible) particles does not have to be carried out to 100%, but is carried out by analysing laboratory samples. Furthermore, the requirement is not "practically free of particles". Non-visible particles are allowed, the limit values depend on the size and the test method used. Particles smaller than 25/50 µm are considered subvisible.

The monographs of the <1788> series are intended to supplement chapters <787>, <788> and <789> with information on sample handling, training of inspectors and details concerning the individual test methods. The revised chapter is a supplement to the chapter <1787> "Measurement of Subvisible Particulate Matter in Therapeutic Protein Injections" which deals with inherent, non-visible particles. Monographs with numbers greater than 1000 are considered informal, non-binding monographs.

The revised chapter <1788> "Methods for the Determination of Subvisible Particulate Matter" is supposed to replace the previous chapter <1788> "Methods for the Determination of Particulate Matter in Injections and Ophthalmic Solutions". The other chapters 1788 1-3 supplement the general chapter by providing detailed information on the individual test methods. The limit values for "Light Obscuration" and Membrane Microscopy have not changed. However, much more information is given than was previously the case. The test method "Flow Imaging" is new and intended as a supporting method. There are no specific limit values for this method yet.

• <1788> Methods for the Determination of Subvisible Particulate Matter
  Includes the consideration of non-ideal (challenging) samples, discussion of the effects of silicone, statistical considerations, control of particulate impurities from the point of view of R&D and commercial operations (similar to USP <1790>) as well as notes on method validation.
• <1788.1> Light Obscuration Method for the Determination of Subvisible Particulate Matter
  Contains now the instruments standardisation as well as instructions for the qualification (IQ/OQ)
• <1788.2> Membrane Microscope Method for the Determination of Subvisible Particulate Matter
  Includes guidance for the qualification of inspectors as well as instructions for the use of automatic inspection systems (detection, sizing, counting)
• <1788.3> Flow Imaging Method for the Determination of Subvisible Particulate Matter
  New method, to support the LO and MM methods

The new chapter drafts are available for free in the Pharmacopeial Forum PF 46(1). You only need to register on the website. Registration is free of charge. The PF website has recently moved, but the previous access data are still valid.