Insoluble particles inspection

(5) Insoluble particles inspection

1.

(1) Insoluble particles are used to check the insoluble particles in intravenous injections (solution injection, sterile powder for injection, concentrated solution for injection) and sterile raw materials for intravenous injection after the inspection of visible foreign bodies meets the requirements.

(2) This method includes two methods: photoresist method and microscopic counting method

(3) The photoresist method is not suitable for preparations that are too viscous and easy to precipitate crystals, nor is it suitable for injections that are easy to generate bubbles when entering the sensor

(4) For injections whose viscosity is too high and cannot be directly measured by the two methods, it can be measured after dilution with a suitable solvent

2.

Test environment and detection: The test operation environment should not introduce foreign particles, and the operation before the test should be carried out on a clean bench

The particle inspection water (or other suitable solvent) meets the following requirements: 50ml measurement by photoresist method, it is required that the number of insoluble particles containing 10um and more than 10um should be less than 10 per 10ml, and the number of insoluble particles containing 25um and more than 25um should be 2 Below

(1) The first method (photoresist method)

1) Intravenous injection or concentrated solution for injection with a labeled volume of 25ml or more: Unless otherwise specified, take at least 4 test samples, wash the outer wall of the container with water, and carefully turn it over 20 times to mix the solution Evenly, open the container immediately and carefully, pour out part of the test solution to rinse the opening and sampling cup, then pour the test solution into the sampling cup, let it stand for 2 minutes or degas for an appropriate time, and place it on the sampler ( Or put the test container directly on the sampler)

2) Intravenous injection or concentrated solution for injection with a labeled volume of less than 25ml: Unless otherwise specified, take at least 4 test samples, wash the outer wall of the container with water, and carefully turn it over 20 times to make the solution evenly mixed.

For example, if the viscosity of the concentrated solution for injection under 1) and 2) is too high to be directly measured, it can be diluted appropriately and measured according to law

3) Sterile powder for intravenous injection: Unless otherwise specified, take at least 4 test samples, wash the outer wall of the container with water, carefully open the bottle cap, precisely add an appropriate amount of water for particle inspection (or a suitable solvent), and cover carefully Put the cap on the bottle, shake it slowly to dissolve the content, let it stand for 2 minutes or degas at an appropriate time, open the container carefully, directly place the test sample container on the sampler, turn on the stirring or turn it slowly by hand to make the solution Mix well (to avoid bubbles), directly draw an appropriate amount of solution from the instrument (without inhaling bubbles), measure and record the data, discard the first measurement data, and take the average of subsequent measurement data as the measurement result

Appropriate methods can also be used to take at least 3 test samples, wash the outer wall of the container with water on a clean workbench, carefully open the cap, and add an appropriate amount of particle inspection water (or a suitable solvent) respectively, and shake slowly Dissolve the contents, carefully combine the solution in the container (to make the total volume not less than 25ml), place it in the sampling cup, let it stand for 2 minutes or degas for an appropriate time, and place it on the sampler

4) Sterile APIs for injection: According to the provisions of each category, take 4 samples of the appropriate amount of the test product (equivalent to the maximum specification of a single preparation), and place them in a sampling cup or a suitable container, according to the above 3) method Begin with "precisely add appropriate amount of water (or suitable solvent) for particle inspection, and slowly shake to dissolve the contents", operate in accordance with the law, measure and record the data, discard the first measurement data, and take the average of the subsequent measurement data as Measurement result

(2) The second method (microscopic counting method)

1) Intravenous injection or concentrated solution for injection with a labeled volume of 25ml or more: Unless otherwise specified, take the test product, wash the outer wall of the container with water, and carefully turn it over 20 times on a laminar flow clean bench.

2) Intravenous injection or concentrated solution for injection with a marked volume of 25ml or less: Unless otherwise specified, take the test sample, wash the outer wall of the container with water, and carefully turn it over 20 times on a clean bench to make the mixture evenly mixed , Immediately open the container carefully, use a suitable method to directly extract all the solution in each container, and slowly pour it into the pretreated filter (filter membrane diameter 13mm) along the inner wall of the filter, and perform the same determination as described in 1) above

3) Sterile powder for intravenous injection and sterile API for injection: Unless otherwise specified, the test solution is prepared according to the 3) or 4) method of the inspection method in the photoresistance method, and the operation is the same as the above 1) method.

.

3.
Matters needing attention

(1) In the microscopic counting method, particles of various shapes should be calculated with the longest measured particle size.
Overlapping particles and polymer colloidal particles are counted as single particles; crystal precipitation is not included in the detection range
.

(2) For formulations with too high viscosity, when neither method can be measured, it can be measured after dilution with an appropriate amount of suitable solvent
.

4.
Results and Judgment

(1) The first method (photoresist method)

1) Intravenous injection with a labelled volume of 100ml or more: Unless otherwise specified, the number of particles containing 10um and more than 10um in 1ml does not exceed 25, and the number of particles containing 25um and more than 25um does not exceed 3 , It was judged to be in compliance with the regulations
.

2) Intravenous injections, sterile powders for intravenous injections, concentrated solutions for injections, and sterile APIs for injections with a marked filling volume of less than 100ml: unless otherwise specified, in each container (portion) of the test product The number of particles containing 10um and above 10um does not exceed 6000 particles, and the number of particles containing 25um and above 25um does not exceed 600 particles, it is judged to meet the requirements
.

(2) The second method (microscopic counting method)

1) Intravenous injection with a labelled volume of 100ml or more: Unless otherwise specified, the number of particles containing 10um and more than 10um in each 1ml does not exceed 12, and the number of particles containing 25um and more than 25um does not exceed 2 , It was judged to be in compliance with the regulations
.

2) Intravenous injections, sterile powders for intravenous injections, concentrated solutions for injections, and sterile APIs for injections with a marked filling volume of less than 100ml: unless otherwise specified, in each container (portion) of the test product The number of particles containing 10um and above 10um does not exceed 3000, and the number of particles containing 25um and above 25μm does not exceed 300, it is judged to meet the requirements
.

5.
Records and calculations

(1) type recording apparatus, the packaging test, the number of tests, injectable sterile powders dissolved, measured by the number and diameter of the filter particles before and after treatment, the test for the number of particles and the like
.

(2) Calculate the number of particles above 10um and above 25um in each 1ml (or each container) of the test product according to the particle value given on the particle analyzer or micro-counter
.

(6) Inspection of related substances in Chinese medicine injections

1.
Brief description

(1) Injection-related substances refer to the substances that may be contained in the injections and need to be controlled after the Chinese medicinal materials and decoction pieces are extracted and purified into injections
.

(2) Unless otherwise specified, a general check of proteins , tannins, resins and the like, intravenous fluids should also check oxalate , potassium ions, polymers and the like
.

2.
The method of operation shall be inspected in accordance with the Inspection Method for Related Substances of Traditional Chinese Medicine Injections (General Rules 2400, 2401, 2402, 2403, 2404, 2405, 2406) and shall meet the requirements
.

3.
Matters needing attention

(1) In the inspection of protein, tannin, resin, and oxalate, if the experimental result is not obvious, use water for injection as a blank, and perform the same method for comparison
.

(2) inspection tannins, containing polyethylene glycol , polysorbate and the like as polyoxyethylene injection group substances, although not tannin precipitation, injection of such semifinished product is to be taken before the additional agent is not added Check
.

(3) During the potassium ion inspection, the standard potassium ion stock solution should be stored in the refrigerator.
Before use, the standard potassium ion stock solution should be accurately measured and freshly diluted and prepared
.

4.
Results and Judgment

(1) Protein, tannin, resin, and oxalate are all checked for turbidity or precipitation, and it is judged as conforming to the regulations, otherwise it is not conforming to the regulations
.

(2) In the potassium ion inspection, the turbidity of the two tubes A and B are compared, and the tube B is shallower than the tube A and judged to meet the requirements
.

The recording and record balance model calculation, the amount of the test sample, the name and amount of the test solution, and the experimental results and the like phenomena
.

(7) Residues of heavy metals and harmful elements

Unless otherwise specified, traditional Chinese medicine injections shall be inspected according to the determination method of lead, cadmium, arsenic, mercury, and copper (General Rule 2321).
According to the maximum daily use amount under each item, lead shall not exceed 12ug, cadmium shall not exceed 3ug, and arsenic shall not exceed If it exceeds 6ug, mercury must not exceed 2ug, and copper must not exceed 150ug
.

(8) Sterile

Unless otherwise specified, injections shall be inspected according to the Sterility Inspection Law (General Rule 1101) and shall meet the requirements
.

(9) Bacterial endotoxin or pyrogen

Unless otherwise specified, intravenous injections shall comply with the requirements of the bacterial endotoxin inspection method (general rule 1143 bacterial endotoxin inspection method) or pyrogen inspection method (general rule 1142) according to the regulations under each category
.

Related link: Inspection of visible foreign body in traditional Chinese medicine