Sources of insoluble particles in injectable drugs and assessment of patient risk (Part 2)

Particles in plastic containers

Plastic particle pollution generally occurs when sharp objects are used through injection ports or from plastic infusion sets. Inserting a needle into the septum or stopper of a medication bottle or infusion container may result in fragments separating from the septum or stopper. The particle may float in the injection solution. If the fragments are small or covered (such as labels or colored vials), contamination may not be detected and may be inhaled into the syringe for injection into the patient's body.

Particles in injection equipment

Infusion is the most common treatment method in China, and studies have shown that the annual use of disposable infusion sets in China exceeds50Billions of them. Are these infusion devices really safe?2017In the annual national reports of adverse events related to medical devices, adverse events related to the use of disposable infusion sets were reported4.35Ten thousand copies, accounting for the total number11.57%It is the medical device with the most problems in China. Therefore, the manufacturing of infusion sets must prevent particle contamination. The Chinese Pharmacopoeia also has clear requirements for this. The particles in medical devices (such as pipes or conduits) used in infusion sets may also have adverse effects on the health of patients, and patients may face contamination risks during infusion due to the particles released by the devices themselves. For this reason, the United StatesFDAIn the production process of medical devices,10–25µmThe particle recovery rate should be at least90%，≥25µmThe lowest particle recovery rate is80%Acceptance criteria. A paper analyzed the level of particle contamination in infusion and hemodialysis catheters. The experiment will inject particle free water into the pipeline and detect particle contamination at different sampling times. Particle free water passing through different porosities（0.8µmThe0.45µmand0.22µm）The filter. Initial particle contamination of the instrument was observed, but the impact on particle contamination of the infusion drug solution was limited.

At present, there is still no unified standard to specify the particle contamination detection method for sterile medical devices and initial packaging materials. For disposable infusion sets and other blood route products, the state-owned standard adopts the method of flushing the surface of the liquid channel in the inner cavity, collecting the flushing liquid through membrane filtration, and conducting detection under a microscopeGB 8368 2005Disposable Infusion Set-Gravity infusion type,GB 19335-2003General technical specifications for disposable blood route products,USP 788Specially designed for injection and non intestinal infusion, it may not always be suitable for medical devices.

The particle contamination of intravenous injection is caused by incomplete recombination of drugs, drug incompatibility reactions during intravenous injection therapy, or component particles in the infusion system. Many studies have found different quantities of plastic particles when analyzing samples at the end connections of infusion tubes.

Lubricants (silicone oil) in pre filled glass syringes may also cause protein aggregation, resulting in particle formation. Silicone resin injectorL-Recombinant induction of protein aggregation by asparaginase. Various techniques can be used to measure the number of particles in protein formulations, but they are not sufficient to characterize particles in various protein solutions. The silicification process may affect the production of particles in protein preparations in pre filled syringes. Adding a certain concentration of surfactants to antibody preparations can reduce particle formation in pre filled glass syringes.

Unsolved solids in drug solutions

Unsolved solids in drug solutions are another source of particle contamination. In the neonatal intensive care unit, a study showed that changes in the dosage of vancomycin injections were mainly caused by the solvent used in the recombinant powder and the lack of systematic stirring to completely dissolve the powder. Through intravenous drug centralized dispensing centerCIVASImproving intravenous medication ensures the microbiological quality and chemical stability of injectable ready to use drugs, which contributes to the quality and efficient management of medical services for hospital patients

Therapeutic protein products may also contain particles inherent to the product. These inherent 'protein' particles are typically different from traditional 'foreign' particles and are more difficult to detect and count. The need to monitor all (foreign and intrinsic) particles in therapeutic protein products has led to the development of measurement techniques. The industrial case study illustrates how to develop sub visible particle analysis strategies to evaluate the properties and quantities of particulate matter, in order to better develop drug products or conduct stability studies. Yinhuang Technology（YinHuang Technology）It owns a series of particle detection equipment with independent intellectual property rights, such asMIPseriesFIPSSeries and various visible foreign object inspection equipment, as well as nano particle size analyzers, enable you to enhance particle detection in the fields of medicine, materials, cosmetics, and semiconductors. Some models and technical parameters are shown in the following figure

MIPSeries insoluble particle detector FIPSSeries flow dynamic image method particle size analyzer

Yinhuang Technology（YinHuang Technology）We are a high-tech company dedicated to providing testing and analysis equipment and technical services for industries such as pharmaceuticals, semiconductors, and chemical materials. We are committed to providing customers with comprehensive and accurate testing, analysis, and solutions. Our main products include insoluble particle analyzer, visible foreign matter inspection analyzer, raw liquid particle size andZetaPotential analyzer,CHDFHigh precision nanometer particle size analyzer, high-resolution nanometer particle size analyzer, solution color analyzer, clarity analyzer, etc., independently developed by the companyYH-MIPSeries Microscopic Counting Insoluble Particle AnalyzerYH-FIPSSeries flow dynamic image method particle size analyzer,YH-FIPSThe series of microfluidic imaging particle analyzers have been widely used in the fields of biomedicine, semiconductors, and materials chemical engineering.