Requirements and instrument recommendations for detecting insoluble particles and foreign objects in therapeutic protein injections in the United States Pharmacopeia（USP787）-Yinhuang Technology provides corresponding solutions

United States Pharmacopeia787（USP787）The section on insoluble particle foreign body detection in therapeutic protein injections is specifically designed for therapeutic protein injections and related formulations, allowing the use of smaller test quantities and fewer test samples to determine the content of insoluble particles, and providing sample handling instructions that consider issues related to the analysis of these materials. Although the methods and limits introduced in this chapter are the first to introduce therapeutic protein injectionsMethod, but using alternative analytical methods with fully developed insoluble particle limits that are acceptable to regulatory authorities is also acceptable.

Therapeutic protein injections are biotechnology derived products of proteins or peptides, as well as other therapeutic protein injections (such as naturally derived therapeutic proteins), including their final infusion formulations. This guideline does not include certain formulations that are not suitable for these trials, such as prophylactic vaccines.

The particles in therapeutic protein injections are composed of mobile undissolved substances, which may come from various sources. Particles may be（a）Real foreign objects, or“foreign object”For example, unexpected foreign substances such as cellulose; （b） Inherent foreign substances are generated due to insufficient addition or cleaning during the manufacturing process, such as tank metal or gaskets, lubricants, filling hardware, or due to instability, such as changes over time, such as insoluble drug salt forms or packaging degradation; And（c）Existing foreign substances, such as protein particles or formula ingredients. All of these particle types can be detected and counted in the experimental methods described in this chapter. In addition, for the photoresist method（LO）Bubbles are usually counted and artifacts are calculated during particle testing, resulting in distorted test results. For the determination of insoluble particles in therapeutic protein injections, the first step is toOptical resistance counting test. In cases where the particles being analyzed are mainly non proteins, or where particle characteristic checks may be important, microscopic counting methods provide more accurate test results. The results of this test are compared to（LO）The test results are more authentic and effective.

It should be noted that inUSP787-Not all therapeutic protein injections can pass the standard for detecting insoluble particles and foreign objects in therapeutic protein injectionsLOMethod: Directly inspect insoluble particles. When the test method is not directly applicable to a specific test sample, as indicated by method validation issues (reproducibility, linearity), appropriate diluents can be used for quantitative dilution for analysis by photoresist method. It may be necessary to validate the insoluble particulate foreign matter method to ensure the appropriateness of sample processing procedures and the performance of testing methods used for each drug.

In the experiments described below, the results obtained by examining the discrete units or unit groups of particulate matter cannot be extrapolated to other untested units with certainty. Therefore, it is necessary to develop a sampling plan based on known operational factors to support effective inference from observational data, in order to characterize the levels of particulate matter in a large number of devices. The sampling plan should be based on considerations of product volume, the number of particles discovered in the past compared to the limit, particle size distribution, and variability in particle numbers between units. Products used in conjunction with the final filter during administration (online) are not subject to these requirements, provided that there is scientific data to justify the exemption.

USP787-Two methods were used to detect insoluble particles and foreign objects in therapeutic protein injections. But the European PharmacopoeiaUSP1788The Japanese Pharmacopoeia recommends the use of microscopic counting method for the detection of insoluble particles and foreign objects in injection solutions.

Optical resistance method insoluble particle inspection test

Analysts should use appropriate instruments based on the principle of photoresist and allow for automatic determination of particle size and quantity. The selected sensor must be suitable for the expected particle size range and expected number of particles. Some standardization steps, such as sample volume accuracy, sample flow rate, sensor resolution, calibration, and particle counting accuracy, are crucial for the correct operation of the instrument and are included in the general information sectionMethods for the Determination of Subvisible Particulate Matter<1788>Further review was conducted.

For equipment calibration purposes, useNISTTraceable granularity standards or equivalent traceable standards, please refer to<1788>. These standards are usually in 2 to100 µmbetween. Analysts should use an appropriate volume dispersed in particle free waterUSPParticle counting is used to verify the performance of the equipment. During the calibration process, attention must be paid to avoiding particle aggregation during dispersion.InReagents, Indicators, and SolutionsThe definition of particle free water is provided in the chapter.

Microscopic Counting Method for Insoluble Particle and Foreign Matter Inspection Test

As mentioned beforeLOFa is the first method of therapeutic protein injections and parenteral infusions. In appropriate circumstances, microscopic counting methods can be used, such as measuring only external and internal particle types. However, it should be demonstrated that when using this method, specific categories of particles (such as intrinsic) are also taken into account. To determine the acceptability of the product, the method of<788>The membrane microscopy test limits in the chapter overview. Due to the interference of certain protein particles and their physical properties (fragile or semi transparent), the results of microscopic counting experiments are not equal to those of photoresist particle counting experiments. Microscopic counting can serve as a validation and supplement to photoresist methods.

Solution:

Yinhuang TechnologyTherapeutic protein injectionThe insoluble particle detection in provides the following products:

1YH-LEIP-0201Optical Resistance Insoluble Particle Analyzer

LEIPThe series of insoluble particle detectors meet the instrument requirements for detecting insoluble particles using the photoresist method in pharmacopoeias of various countries. They can directly detect the content and size of insoluble particles in injection solutions, sterile powders, infusion equipment, and drug packaging materials. The instrument adopts high-performance imported laser light source and compensation circuit to ensure the testing accuracy of various colorless and colored samples. The injection slit and pipeline are imported316LAnd importsPTFEThe material can directly detect special solutions such as organic solvents and oil matrices.

2TheYH-MIP-0103Microscopic Counting Insoluble Particle Analyzer

Technical advantages:

A fully automated testing system that automatically scans, counts, and issues reports, reducing human error in operation

√ Fully automatic detection system, reducing eye damage to testers during use

√ Can distinguish particle properties, identify the source of insoluble particles, whether they are metals or fibers

√ Complies with the pharmacopoeias of various countries such as the Chinese Pharmacopoeia, the United States Pharmacopoeia, the European Pharmacopoeia, and the Japanese PharmacopoeiaChineseForMicroscopic counting methodInsoluble particle inspectioninstrumentrequirement

3TheYH-MIP-0205ProMicroscopic Counting Insoluble Particle Analyzer

YH-MIP-0205 ProThe Type Micro Counting Insoluble Particle Analyzer is a new generation of insoluble particle analyzer that can automatically detect insoluble particles in samplesAutomatic filtering, drying, testing, and report issuanceWaiting for multiple processes; Super-resolution algorithmAIThe introduction of various image processing methods such as intelligent algorithms can effectively ensure the accuracy of test data. Complies with the instrument requirements for insoluble particle detection using microscopic counting method in pharmacopoeias of various countries such as the Chinese Pharmacopoeia, the United States Pharmacopoeia, the European Pharmacopoeia, and the Japanese Pharmacopoeia.