Tepnel is excited to announce that the small volume sub-visible particle adaptor for our HIAC instrument is now installed and qualified, ready to enhance our analytical testing to further meet your needs.
To find out more about how we can support your drug development pipeline please get in touch using the form below, and a member of the team will be in touch.
USP <787> can be used as an alternative to USP general chapter USP <788> Particulate Matter in Injections. USP chapter <787>, Subvisible Particulate Matter in Therapeutic Protein Injections, which became official August 1, 2014, provides specific guidance for protein-based formulations. Chapter <787> evolved to address the limitations of USP for therapeutic proteins and provides a smaller-volume testing framework to address proteinaceous particles and the immunological effects of a sub-10-µm particle load 1.
For USP <788> the nominal test volume is 30mls. The benefit to the customer is, by using the small volume sub-visible particle adaptor test volumes can be reduced to between 1.5ml – 5mls, thus providing a cost saving to our customers and reducing sample sizes for small batch manufacture.
The USP says that method verification maybe required to ensure the appropriateness of sample handling procedures and performance of the method for each drug product through reproducibility and linearity checks 2.
Testing must be performed under conditions that limit ingress of particulate matter, preferably in a laminar-flow cabinet. The glassware and equipment used should be properly cleaned and handled to remain particle free. Care should be taken to minimize shaking and other stresses to the preparations (for liquids or reconstituted powders) and to prevent introduction of air bubbles into the preparation under examination. This is particularly important when preparations are combined or transferred to the container in which the determination will be carried out. Eliminating gas bubbles is a key step particularly for proteinaceous products that readily entrain gas. Two methods recommended are allowing the product to stand under ambient pressure or applying a gentle vacuum (e.g. 75 torr). Once samples have been degassed, they must be mixed gently to re-suspend all particles. Inversion to mix the product fluid is not recommended at any time.
Dilution of the sample is allowed if the diluent and methods are demonstrated to be appropriate and the smallest level of dilution that allows for reproducible testing is used. Under certain circumstances dilution of samples may be required to obtain reliable results. This may be the case with high-concentration products and/or high-viscosity products that cannot be drawn into the instrument properly; products that cause saturation of the instrument sensor due to high counts, especially in the smaller than 10-µm size ranges; and cases where the high concentration results in very small differences in refractive index between the solution and the protein aggregates, etc. However, suitability of the selected dilution scheme including choice of diluent must be demonstrated.
The USP sets the following limits for the test depending on container size: 2
For parenteral products that are therapeutic protein injections for infusion or injection supplied in containers with a nominal content of less than or equal to 100 mL the average number of particles present in the units tested should not exceed 6000 per container equal to or greater than 10 µm and should not exceed 600 per container equal to or greater than 25 µm.
For therapeutic protein injections supplied in containers with a nominal content of more than 100 mL, and parenteral infusion preparations or injections with a nominal content of more than 100 mL the average number of particles present in the units tested should not exceed 25/mL equal to or greater than 10 µm and should not exceed 3/mL equal to or greater than 25 µm. Also, total particle load should not exceed 6000 per container equal to or greater than 10 µm and should not exceed 600 per container equal to or greater than 25 µm.
1. Beckman Coulter https://www.beckman.com/resources/industry-standards/usp-787/subvisible-particulate-matter-in-therapeutic-protein-injections
2. United States Pharmacopoeia <787> SUBVISIBLE PARTICULATE MATTER IN THERAPEUTIC PROTEIN INJECTIONS