Why is particulate matter testing crucial for injectable medicines, and what does it entail?

The American USP’s requirements for injectable particulate matter testing are in line with those of the European and Japanese Pharmacopeias. In injectable solutions, undissolved particles (apart from gas bubbles) are referred to as particulate matter. The parenteral formulation does not purposefully contain these particle materials. Unintentional, non-biological particles are controlled in injectable formulations to prevent undesirable toxicity, disease, or side effects, much like unintended microorganisms are avoided and controlled in injectables to prevent patient illness. The USP 788 particle matter regulation standards are not applicable to persons making parenteral medications for veterinary use, solutions for irrigation only, or radiopharmaceutical preparations. Your injectable product might be free from particulate matter regulations if it filters before being administered to patients, as long as there is scientific evidence to support the exemption. Please take note that injectable and parenteral will be used interchangeably in this text. Therefore, the words “small-volume injection” and “small-volume parenteral” are interchangeable.

Both a tiny particle count test and a light-obscuration particle count test are used to identify particulate pollution. Subvisible particles in injections and parenteral infusions are best detected by light-obscuration particle count tests. Microscopic particle count tests should be used to evaluate parenteral preparations with reduced clarity or increased viscosity, such as emulsions, colloids, and liposomal formulations. Products that frequently create air or gas bubbles during sampling can also benefit from microscopic particle count testing. In certain situations, confirming subvisible particle counts will require the use of both particulate matter test methods. Additionally, many injectable formulations could be challenging to evaluate using both conventional particle matter testing techniques. In these specific situations, which frequently occur when the test preparation’s viscosity is high, a quantitative dilution with the proper diluent may be done to reduce viscosity as needed to enable the particle analysis.

How is light obscuration used in particulate matter testing?

The liquid particle counting machine used in light obscuration particulate matter testing uses the theory of light scattering to automatically determine the size of particles in a sample and the number of particles depending on size. Spherical particle dispersions in particle-free water are used to calibrate the liquid particle counter. The known diameters of these spherical particles range from 10 microns (μm) to 25 μm. All glassware and testing apparatus are cleaned with particle-free water prior to use. In order to ensure that no more than 25 particles measuring 10 μm or larger are detected in particle-free controls in triplicate, particle-free water samples are checked once equipment is set up. The testing apparatus will be cleaned and recalibrated prior to sample testing if more particles are found.

Slow inversion is used to mix the contents of each sample for testing. Care is made to avoid adding air bubbles to the preparations being inspected. Samples can be sonicated or let to stand for two minutes after inversion to further remove gas bubbles. The contents of 10 or more units are mixed in a sanitized container to provide a volume of at least 25 milliliters (mL) for small-volume parenterals (less than 25 mL in volume). When particle-free water is not suitable, parenteral powders are reconstituted using particle-free water or an appropriate particle-free solvent. Individual tests are performed on injectables having a capacity of 25 mL or greater. Compute the test result on a section equal to the maximum labeled dose for pharmacy bulk packages marked “Not for Direct Infusion.” To find the particle count for the 10-mL maximum dose, for instance, you would multiply the particle count per mL by 10 if the average particle count per mL is 5. The highest dose of 10 mL in this example has a particle count of 50. Depending on the container volume, items intended to house a drug product and a solvent should be tested as specified for either large-volume parenteral or small-volume parenteral products.

For the evaluation to be statistically sound, there must be a sufficient number of samples. Less than ten separate units may be evaluated for injectables having a capacity of 25 mL or more.

Count the number of particles that are equal to or larger than 10 μm and 25 μm after carefully mixing and removing four sections, each containing at least 5 mL. Determine the preparation’s mean particle count for examination.

Determine the sample’s mean particle count once the particles have been counted. There are two test criteria for light obscuration particle count tests. The first test criterion is applicable to sample preparations that have a volume greater than 100 mL. The second test criterion is applied to samples that have a volume of less than 100 mL. If the average number of particles in the units tested is less than 25 particles per milliliter (mL) equal to or more than 10 μm and less than 3 particles per milliliter (mL) equal to or greater than 25 μm, the sample satisfies the particle count test in the first test criterion. If the average number of particles tested in a container does not exceed 6000 particles equal to or more than 10 μm, or 600 particles per container equal to or greater than 25 μm, the sample satisfies the second test criterion. Use the microscopic particle count test on the samples if the average number of particles is higher than the allowable limits.

In Brief

particulate matter testing is an essential injectable microbiological test. Injectable formulations control unintended, non-biological particles to avoid unintended toxicity, disease, or adverse consequences in patients after therapy. Particulate matter can be tested using two different methods: the tiny particle count test and the light-obscuration particle count test. Except in cases where preparations are too hazy or viscous for precise particle identification, light-obscuration particle count techniques are employed. All things considered, when creating your injectable product, make sure you pick a contract testing company that can help you with the right microbiology testing for your particular product or medical device requirements.