2.9.19. PARTICULATE CONTAMINATION: SUB-VISIBLE PARTICLES

2.9.19. 顆粒物污染：亞可見(jiàn)顆粒物檢查規(guī)定

Particulate contamination of injections and infusions consists of extraneous, m o bile undissolved particles, other than gas bubbles, unintentionally present in the solutions.

注射劑和輸液的微粒污染包括在溶液中無(wú)意中存在的外來(lái)的、可移動(dòng)的未溶解顆粒，而不是氣泡。

For the determination of particulate contamination 2 procedures, Method 1 (Light Obscuration Particle Count Test) and Method 2 (Microscopic Particle Count Test), are specified hereinafter. When examining injections and infusions for sub-visible particles, Method 1 is preferably applied. However, it may be necessary to test some preparations by the light obscuration particle count test followed by the microscopic particle count test to reach a conclusion on conformance to the requirements.

對(duì)于顆粒物污染的測(cè)定包含兩種方法，下文進(jìn)行了詳細(xì)介紹：方法1（光阻法顆粒計(jì)數(shù)試驗(yàn)）和方法2（顯微顆粒物計(jì)數(shù)試驗(yàn)）。當(dāng)檢查注射劑和輸液中是否存在亞可見(jiàn)顆粒時(shí)，最好使用方法1。然而，可能有必要通過(guò)光阻法顆粒計(jì)數(shù)試驗(yàn)和顯微顆粒計(jì)數(shù)試驗(yàn)來(lái)測(cè)試某些制劑，以得出符合要求的結(jié)論。

Not all parenteral preparations can be examined for sub-visible particles by one or both of these methods. When Method 1 is not applicable, e.g. in case of preparations having reduced clarity or increased viscosity, the test is carried out according to Method 2. Emulsions, colloids, and liposomal preparations are examples. Similarly, products that produce air or gas bubbles when drawn into the sensor may also require microscopic particle count testing. If the viscosity of the preparation to be tested is sufficiently high so as to preclude its examination by either test method, a quantitative dilution with an appropriate diluent may be made to decrease viscosity, as necessary, to allow the analysis to be performed.

并非所有非腸道制劑都可以通過(guò)這些方法中的一種或兩種方法檢查亞可見(jiàn)顆粒。例如在制劑的透明度降低或粘度增加的情況下，方法 1 不適用時(shí)，應(yīng)根據(jù)方法2進(jìn)行測(cè)試，如乳液、膠體和脂質(zhì)體制劑等。 同樣，在吸入傳感器時(shí)會(huì)產(chǎn)生空氣或氣泡的產(chǎn)品也可能需要進(jìn)行顯微顆粒物計(jì)數(shù)測(cè)試。 如果待測(cè)制劑的粘度足夠高以至于無(wú)法通過(guò)任一測(cè)試方法對(duì)其進(jìn)行檢查，則可以根據(jù)需要，用適當(dāng)?shù)南♂寗┻M(jìn)行定量稀釋以降低粘度，以便進(jìn)行分析。

The results obtained in examining a discrete unit or group of units for particulate contamination cannot be extrapolated with certainty to other units that remain untested. Thus, statistically sound sampling plans must be developed if valid inferences are to be drawn from observed data to characterize the level of particulate contamination in a large group of units.

在檢查一個(gè)離散單元或一組單元的微粒污染時(shí)獲得的結(jié)果不能肯定地外推到其他未測(cè)試的單元。 因此，如果要從觀察到的數(shù)據(jù)中得出有效的推論，以表征一大組單位中的顆粒污染水平，就必須制定統(tǒng)計(jì)上合理的抽樣計(jì)劃。

METHOD 1. LIGHT OBSCURATION PARTICLE COUNTTEST

光阻法顆粒計(jì)數(shù)實(shí)驗(yàn)

Use a suitable apparatus based on the principle of light blockage which allows an automatic determination of the size of particles and the number of particles according to size. The apparatus is calibrated using suitable certified reference materials consisting of dispersions of spherical particles of known sizes between 10 µm and 25 µm. These standard particles are dispersed in particle-free water R. Care must be taken to avoid aggregation of particles during dispersion.

根據(jù)光阻原理，使用合適的儀器，可以根據(jù)大小自動(dòng)確定顆粒大小和顆粒數(shù)量。使用合適的認(rèn)證標(biāo)準(zhǔn)物質(zhì)對(duì)儀器進(jìn)行校準(zhǔn)，該標(biāo)準(zhǔn)物質(zhì)由已知尺寸在10 µm到25 µm之間的球形顆粒的分散體組成。這些標(biāo)準(zhǔn)顆粒分散在無(wú)顆粒水中。分散過(guò)程中必須注意避免顆粒聚集。

General precautions 一般注意事項(xiàng)

The test is carried out under conditions limiting particulate contamination, preferably in a laminar-flow cabinet. Very carefully wash the glassware and filtration equipment used, except for the membrane filters, with a warm detergent solution and rinse with abundant amounts of water to remove all traces of detergent. Immediately before use, rinse the equipment from top to bottom, outside and then inside, with particle-free water R.

實(shí)驗(yàn)在限制顆粒污染的條件下進(jìn)行，最好在層流柜中進(jìn)行。使用溫?zé)岬那鍧崉┤芤鹤屑?xì)清洗所用的玻璃器皿和過(guò)濾設(shè)備（膜式過(guò)濾器除外），并用大量水沖洗，以去除所有清潔劑痕跡。使用前，用無(wú)顆粒水從上到下、從外到內(nèi)沖洗設(shè)備。

Take care not to introduce air bubbles into the preparation to be examined, especially when fractions of the preparation are being transferred to the container in which the determination is to be carried out.

注意不要將氣泡引入待檢查的制劑中，尤其是將制劑的部分轉(zhuǎn)移到要進(jìn)行測(cè)定的容器中時(shí)。

In order to check that the environment is suitable for the test, that the glassware is properly cleaned and that the water to be used is particle-free, the following test is carried out: determine the particulate contamination of 5 samples of particle-free water R, each of 5 mL, according to the method described below. If the number of particles of 10 µm or greater size exceeds 25 for the combined 25 mL, the precautions taken for the test are not sufficient. The preparatory steps must be repeated until the environment, glassware and water are suitable for the test。

為了檢查環(huán)境是否適合試驗(yàn)，玻璃器皿是否正確清潔，所使用的水是否無(wú)顆粒，應(yīng)進(jìn)行以下試驗(yàn)：根據(jù)下述方法，測(cè)定5個(gè)無(wú)顆粒水樣品的顆粒污染情況，每個(gè)樣品5 mL。如果10 µm或更大粒徑的顆粒數(shù)量超過(guò)25個(gè)，則為試驗(yàn)采取的預(yù)防措施是不夠的。必須重復(fù)準(zhǔn)備步驟，直到環(huán)境、玻璃器皿和水適合試驗(yàn)

Method方法

Mix the contents of the sample by slowly inverting the container 20 times successively. If necessary, cautiously remove the sealing closure. Clean the outer surfaces of the container opening using a jet of particle-free water R and remove the closure, avoiding any contamination of the contents. Eliminate gas bubbles by appropriate measures such as allowing to stand for 2 min or sonicating.

通過(guò)連續(xù)20次緩慢翻轉(zhuǎn)容器，混合樣品里的內(nèi)容物。如有必要，小心地拆下密封蓋。使用無(wú)顆粒水水流清潔容器開(kāi)口的外表面，并拆下封蓋，避免內(nèi)容物受到任何污染。通過(guò)適當(dāng)?shù)拇胧┫龤馀?，例如靜置2分鐘或超聲波處理。

For large-volume parenterals, single units are tested. For small-volume parenterals less than 25 mL in volume, the contents of 10 or more units are combined in a cleaned container to obtain a volume of not less than 25 mL; where justified and authorised, the test solution may be prepared by mixing the contents of a suitable number of vials and diluting to 25 mL with particle-free water R or with an appropriate solvent without contamination of particles when particle-free water R is not suitable. Small-volume parenterals having a volume of 25 mL or more may be tested individually.

對(duì)于大容量腸外注射劑，需要測(cè)試單個(gè)單元。對(duì)于體積小于25 mL的小容量腸外注射劑，將10個(gè)或更多個(gè)的內(nèi)容物組合在一個(gè)清潔的容器中，以獲得不小于25 mL的體積的溶液；在合理和授權(quán)的情況下，可通過(guò)混合適當(dāng)數(shù)量的小瓶中的內(nèi)容物，并用無(wú)顆粒水稀釋至25 mL，或在無(wú)顆粒水不適用時(shí)，用無(wú)顆粒污染的適當(dāng)溶劑稀釋至25 mL來(lái)制備試驗(yàn)溶液。體積為25 mL或以上的小容量非腸道藥物試劑可單獨(dú)進(jìn)行試驗(yàn)。

Powders for parenteral administration are reconstituted with particle-free water R or with an appropriate solvent without contamination of particles when particle-free water R is not suitable.

用于腸外給藥的粉末用無(wú)顆粒水重新配制，或當(dāng)無(wú)顆粒水不適用時(shí)，使用適當(dāng)?shù)臒o(wú)顆粒污染的溶劑重新進(jìn)行配制。

The number of test specimens must be adequate to provide a statistically sound assessment. For large-volume parenterals or for small-volume parenterals having a volume of 25 mL or more, fewer than 10 units may be tested, based on an appropriate sampling plan。

測(cè)試樣本的數(shù)量必須足夠，以提供統(tǒng)計(jì)上合理的評(píng)估。根據(jù)適當(dāng)?shù)某闃佑?jì)劃，對(duì)于大容量或25 mL以上的小容量腸外靜脈，可檢測(cè)小于10個(gè)樣品

Remove 4 portions, each of not less than 5 mL, and count the number of particles equal to or greater than 10 µm and 25 µm. Disregard the result obtained for the first portion, and calculate the mean number of particles for the preparation to be examined.

取下4份樣品，每份不少于5 mL，并計(jì)算等于或大于10 µm和25 µm的顆粒數(shù)。忽略第一份的結(jié)果，并計(jì)算待檢查制劑的平均顆粒數(shù)。

Evaluation評(píng)估

For preparations supplied in containers with a nominal volume of more than 100 mL, apply the criteria of test 1.A.

For preparations supplied in containers with a nominal volume of less than 100 mL, apply the criteria of test 1.B.

?For preparations supplied in containers with a nominal volume of 100 mL, apply the criteria of test 1.B. ?

If the average number of particles exceeds the limits, test the preparation by the microscopic particle count test.

對(duì)于在標(biāo)稱(chēng)體積超過(guò)100 mL的容器中提供的制劑，應(yīng)采用試驗(yàn)1A的標(biāo)準(zhǔn)。

對(duì)于在標(biāo)稱(chēng)體積小于100 mL的容器中提供的制劑，采用試驗(yàn)1B的標(biāo)準(zhǔn)。

對(duì)于在標(biāo)稱(chēng)體積為100 mL的容器中提供的制劑，采用試驗(yàn)1B的標(biāo)準(zhǔn)。

如果平均顆粒數(shù)超過(guò)限值，則通過(guò)顯微顆粒計(jì)數(shù)測(cè)試對(duì)制劑進(jìn)行測(cè)試。

Test 1.A – Solutions for infusion or solutions for injection supplied in containers with a nominal content of more than 100 mL

The preparation complies with the test if the average number of particles present in the units tested does not exceed 25 per millilitre equal to or greater than 10 µm and does not exceed 3 per millilitre equal to or greater than 25 µm.

試驗(yàn)1A–輸液溶液或注射溶液，裝在標(biāo)稱(chēng)含量超過(guò)100 mL的容器中。

如果被測(cè)單位樣品中粒徑等于或大于10 µm的顆粒的平均數(shù)量不超過(guò)每毫升25個(gè)，且粒徑等于或大于25 µm的顆粒平均數(shù)量不超過(guò)每毫升3個(gè)，則制劑符合試驗(yàn)要求。

Test 1.B – Solutions for infusion or solutions for injection supplied in containers with a nominal content of less than 100 mL

The preparation complies with the test if the average number of particles present in the units tested does not exceed 6000 per container equal to or greater than 10 µm and does not exceed 600 per container equal to or greater than 25 µm.

試驗(yàn)1B–輸液溶液或注射溶液，裝在標(biāo)稱(chēng)含量小于100 mL的容器中。

如果被測(cè)單元中粒徑等于或大于10 µm的顆粒的平均數(shù)量不超過(guò)6000個(gè)/容器，且粒徑等于或大于25 µm的顆粒平均數(shù)量不超過(guò)600個(gè)/容器，則制劑符合試驗(yàn)要求。

METHOD 2. MICROSCOPIC PARTICLE COUNT TEST

顯微顆粒計(jì)數(shù)

Use a suitable binocular microscope, filter assembly for retaining particulate contamination and membrane filter for examination.

使用合適的雙目顯微鏡、過(guò)濾器組件（用于保留顆粒污染物）和薄膜過(guò)濾器（用于檢查）。

The microscope is equipped with an ocular micrometer calibrated with an objective micrometer, a mechanical stage capable of holding and traversing the entire filtration area of the membrane filter, 2 suitable illuminators to provide episcopic illumination in addition to oblique illumination, and is adjusted to 100 ± 10 magnifications.

該顯微鏡配有一個(gè)目鏡測(cè)微計(jì)（使用物鏡測(cè)微計(jì)校準(zhǔn)）、一個(gè)機(jī)械工作臺(tái)（能夠容納并穿過(guò)膜過(guò)濾器的整個(gè)過(guò)濾區(qū)域）、2個(gè)合適的照明器（除了傾斜照明外，還提供反射照明），并將其調(diào)整為100±10倍。

The ocular micrometer is a circular diameter graticule (see Figure 2.9.19.-1.) and consists of a large circle divided by crosshairs into quadrants, transparent and black reference circles 10 µm and 25 µm in diameter at 100 magnifications, and a linear scale graduated in 10 µm increments. It is calibrated using a stage micrometer that is certified by either a domestic or international standard institution. A relative error of the linear scale of the graticule within ± 2 per cent is acceptable. The large circle is designated the graticule field of view (GFOV).

目鏡測(cè)微計(jì)是一個(gè)圓形直徑分劃器（見(jiàn)圖2.9.19.-1）由一個(gè)被十字準(zhǔn)線(xiàn)分成四個(gè)象限的大圓、100倍放大時(shí)直徑為10 µm和25 µm的透明和黑色參考圓、以及以10 µm增量刻度的線(xiàn)性刻度組成。使用經(jīng)過(guò)國(guó)內(nèi)或國(guó)際標(biāo)準(zhǔn)機(jī)構(gòu)認(rèn)證的測(cè)微計(jì)對(duì)其進(jìn)行校準(zhǔn)。分劃線(xiàn)性刻度的相對(duì)誤差在±2%以?xún)?nèi)是可以接受的。大圓被designated為網(wǎng)格視場(chǎng)（GFOV）。

2 illuminators are required. One is an episcopic brightfield illuminator internal to the microscope, the other is an external, focusable auxiliary illuminator adjustable to give reflected oblique illumination at an angle of 10-20°.

需要2個(gè)照明器。一個(gè)是顯微鏡內(nèi)部的一個(gè)反射式亮場(chǎng)照明器，另一個(gè)是一個(gè)可調(diào)的外部可聚焦輔助照明器，以提供10-20°角的反射斜照明。

The filter assembly for retaining particulate contamination consists of a filter holder made of glass or other suitable material, and is equipped with a vacuum source and a suitable membrane filter.

用于保留顆粒污染物的過(guò)濾器組件包括由玻璃或其他合適材料制成的過(guò)濾器支架，并配備有真空源和合適的膜過(guò)濾器。

The membrane filter is of suitable size, black or dark grey in colour, non-gridded or gridded, and 1.0 µm or finer in nominal pore size.

膜過(guò)濾器尺寸合適，顏色為黑色或深灰色，無(wú)網(wǎng)格或網(wǎng)格，標(biāo)稱(chēng)孔徑為1.0 µm或更小。

General precautions 一般注意事項(xiàng)

The test is carried out under conditions limiting particulate contamination, preferably in a laminar-flow cabinet.

Very carefully wash the glassware and filter assembly used, except for the membrane filter, with a warm detergent solution and rinse with abundant amounts of water to remove all traces of detergent. Immediately before use, rinse both sides of the membrane filter and the equipment from top to bottom, outside and then inside, with particle-free water R.

試驗(yàn)在限制顆粒污染的條件下進(jìn)行，最好在層流柜中進(jìn)行。

使用溫?zé)岬那鍧崉┤芤鹤屑?xì)清洗所用的玻璃器皿和過(guò)濾器組件（膜式過(guò)濾器除外），并用大量水沖洗，以去除所有清潔劑痕跡。使用前，用無(wú)顆粒水從上到下、從外到內(nèi)沖洗膜過(guò)濾器和設(shè)備的兩側(cè)。

In order to check that the environment is suitable for the test, that the glassware and the membrane filter are properly cleaned and that the water to be used is particle-free, the following test is carried out: determine the particulate contamination of a 50 mL volume of particle-free water R according to the method described below. If more than 20 particles 10 µm or larger in size or if more than 5 particles 25 µm or larger in size are present within the filtration area, the precautions taken for the test are not sufficient. The preparatory steps must be repeated until the environment, glassware, membrane filter and water are suitable for the test.

為了檢查環(huán)境是否適合試驗(yàn)，玻璃器皿和膜過(guò)濾器是否正確清潔，所使用的水是否無(wú)顆粒，應(yīng)進(jìn)行以下試驗(yàn)：根據(jù)下述方法測(cè)定50 mL無(wú)顆粒水的顆粒污染情況。如果過(guò)濾區(qū)域內(nèi)存在20個(gè)以上粒徑為10 µm或更大的顆粒，或5個(gè)以上粒徑為25 µm或更大的顆粒，則試驗(yàn)所采取的預(yù)防措施是不夠的。必須重復(fù)準(zhǔn)備步驟，直到環(huán)境、玻璃器皿、膜過(guò)濾器和水適合試驗(yàn)。

Method方法

Mix the contents of the samples by slowly inverting the container 20 times successively. If necessary, cautiously remove the sealing closure. Clean the outer surfaces of the container opening using a jet of particle-free water R and remove the closure, avoiding any contamination of the contents.

通過(guò)將容器連續(xù)緩慢翻轉(zhuǎn)20次來(lái)混合樣品內(nèi)容物。如有必要，小心地拆下密封蓋。使用無(wú)顆粒水水流清潔容器開(kāi)口的外表面，并拆下封蓋，避免內(nèi)容物的任何污染。

For large-volume parenterals, single units are tested. For small-volume parenterals less than 25 mL in volume, the contents of 10 or more units are combined in a cleaned container; where justified and authorised, the test solution may be prepared by mixing the contents of a suitable number of vials and diluting to 25 mL with particle-free water R or with an appropriate solvent without contamination of particles when particle-free water R is not suitable. Small-volume parenterals having a volume of 25 mL or more may be tested individually.

對(duì)于大容量腸外注射，需要測(cè)試單個(gè)樣品。對(duì)于體積小于25 mL的小容量腸外注射劑，將10個(gè)或更多個(gè)的樣品組合在一個(gè)清潔的容器中；在合理和授權(quán)的情況下，可通過(guò)混合適當(dāng)數(shù)量的小瓶中的內(nèi)容物，并用無(wú)顆粒水稀釋至25 mL，當(dāng)無(wú)顆粒水不適用時(shí)，可用無(wú)顆粒污染的適當(dāng)溶劑稀釋至25 mL來(lái)制備試驗(yàn)溶液。體積為25 mL或以上的小容量非腸道藥物可單獨(dú)進(jìn)行試驗(yàn)。

Powders for parenteral administration are constituted with particle-free water R or with an appropriate solvent without contamination of particles when particle-free water R is not suitable.

用于腸外給藥的粉末由無(wú)顆粒水配置，或當(dāng)無(wú)顆粒水不適用時(shí)，使用不含污染顆粒的溶劑重新配制。

The number of test specimens must be adequate to provide a statistically sound assessment. For large-volume parenterals or for small-volume parenterals having a volume of 25 mL or more, fewer than 10 units may be tested, based on an appropriate sampling plan.

試樣數(shù)量必須足以提供統(tǒng)計(jì)上合理的評(píng)估。對(duì)于大容量腸外注射劑或體積大于等于25 mL的小容量腸外注射劑，根據(jù)適當(dāng)?shù)娜佑?jì)劃，可測(cè)試少于10個(gè)樣品。

Wet the inside of the filter holder fitted with the membrane filter with several millilitres of particle-free water R. Transfer to the filtration funnel the total volume of a solution pool or of a single unit, and apply vacuum. If needed, add stepwise a portion of the solution until the entire volume is filtered. After the last addition of solution, begin rinsing the inner walls of the filter holder by using a jet of particle-free water R. Maintain the vacuum until the surface of the membrane filter is free from liquid. Place the filter in a Petri dish and allow the filter to air-dry with the cover slightly ajar. After the filter has been dried, place the Petri dish on the stage of the microscope, scan the entire membrane filter under the reflected light from the illuminating device, and count the number of particles that are equal to or greater than 10 µm and the number of particles that are equal to or greater than 25 µm. Alternatively, partial filter count and determination of the total filter count by calculation is allowed. Calculate the mean number of particles for the preparation to be examined.

用幾毫升無(wú)顆粒水濕潤(rùn)裝有薄膜過(guò)濾器的過(guò)濾器支架內(nèi)部。將溶液或單個(gè)樣品轉(zhuǎn)移到過(guò)濾漏斗中，并施加真空。如果需要，逐步添加一部分溶液，直到整個(gè)體積被過(guò)濾。最后一次添加溶液后，使用無(wú)顆粒水水流開(kāi)始沖洗過(guò)濾器支架的內(nèi)壁。保持真空，直到過(guò)濾膜表面沒(méi)有液體。將過(guò)濾膜放置在有蓋培養(yǎng)皿中，讓過(guò)濾膜風(fēng)干，蓋子稍微半開(kāi)。過(guò)濾膜干燥后，將皮氏培養(yǎng)皿放在顯微鏡臺(tái)上，在照明設(shè)備的反射光下掃描整個(gè)膜過(guò)濾器，并計(jì)算等于或大于10 µm的顆粒數(shù)量和等于或大于25 µm的顆粒數(shù)量。或者，如果計(jì)算方式允許，可以對(duì)部分濾膜上的顆粒計(jì)數(shù)，并決定總濾膜上的顆粒數(shù)量。計(jì)算待檢查制劑的平均顆粒數(shù)。

The particle sizing process with the use of the circular diameter graticule is carried out by transforming mentally the image of each particle into a circle and then comparing it to the 10 µm and 25 µm graticule reference circles. Thereby the particles are not moved from their initial locations within the graticule field of view and are not superimposed on the reference circles for comparison. The inner diameter of the transparent graticule reference circles is used to size white and transparent particles, while dark particles are sized by using the outer diameter of the black opaque graticule reference circles.

通過(guò)將每個(gè)顆粒的圖像轉(zhuǎn)換成一個(gè)圓，然后將其與10 µm和25 µm的分劃參考圓進(jìn)行比較，使用圓形直徑分劃的顆粒尺寸來(lái)執(zhí)行顆粒尺寸測(cè)定過(guò)程。因此，粒子不會(huì)從網(wǎng)格視場(chǎng)內(nèi)的初始位置移動(dòng)，也不會(huì)疊加在參考圓上進(jìn)行比較。透明分劃參考圓的內(nèi)徑用于確定白色和透明粒子的大小，而黑色粒子的大小則使用黑色不透明分劃參考圓的外徑進(jìn)行確定。

In performing the microscopic particle count test do not attempt to size or enumerate amorphous, semi-liquid, or otherwise morphologically indistinct materials that have the appearance of a stain or discoloration on the membrane filter. These materials show little or no surface relief and present a gelatinous or film-like appearance. In such cases the interpretation of enumeration may be aided by testing a sample of the solution by the light obscuration particle count test.

在進(jìn)行微觀顆粒計(jì)數(shù)試驗(yàn)時(shí)，不要試圖測(cè)量或列舉無(wú)定形、半液體或其他形態(tài)不明顯的材料，這些材料在膜過(guò)濾器上出現(xiàn)污漬或變色。這些材料很少或沒(méi)有表面浮雕，呈現(xiàn)膠狀或薄膜狀外觀。在這種情況下，可通過(guò)光阻法粒子計(jì)數(shù)測(cè)試溶液樣品來(lái)輔助解釋計(jì)數(shù)。

Evaluation評(píng)估

For preparations supplied in containers with a nominal volume of more than 100 mL, apply the criteria of test 2.A.

For preparations supplied in containers with a nominal volume of less than 100 mL, apply the criteria of test 2.B.

?For preparations supplied in containers with a nominal volume of 100 mL, apply the criteria of test 2B.?

If the average number of particles exceeds the limits, test the preparation by the microscopic particle count test.

對(duì)于在標(biāo)稱(chēng)體積大于100 mL的容器中提供的制劑，應(yīng)采用試驗(yàn)2 A.的標(biāo)準(zhǔn)。

對(duì)于在標(biāo)稱(chēng)體積小于100 mL的容器中提供的制劑，采用試驗(yàn)2 B的標(biāo)準(zhǔn)。

?對(duì)于在標(biāo)稱(chēng)體積為100 mL的容器中提供的制劑，采用試驗(yàn)2 B的標(biāo)準(zhǔn)。?

如果平均顆粒數(shù)超過(guò)限值，則通過(guò)顯微顆粒計(jì)數(shù)測(cè)試對(duì)制劑進(jìn)行測(cè)試。

Test 2.A – Solutions for infusion or solutions for injection supplied in containers with a nominal content of more than 100 mL.

The preparation complies with the test if the average number of particles present in the units tested does not exceed 12 per millilitre equal to or greater than 10 µm and does not exceed 2 per millilitre equal to or greater than 25 µm.

試驗(yàn)2A–輸液溶液或注射溶液，裝在標(biāo)稱(chēng)含量超過(guò)100 mL的容器中。

如果被測(cè)單位中顆粒尺寸等于或大于10 µm的平均數(shù)量不超過(guò)每毫升12個(gè)，且顆粒尺寸等于或大于25 µm的平均數(shù)量不超過(guò)每毫升2個(gè)，則制劑符合試驗(yàn)要求。

Test 2.B – Solutions for infusion or solutions for injection supplied in containers with a nominal content of less than 100 mL

The preparation complies with the test if the average number of particles present in the units tested does not exceed 3000 per container equal to or greater than 10 µm and does not exceed 300 per container equal to or greater than 25 µm.

試驗(yàn)2B–在標(biāo)稱(chēng)含量小于100 mL的容器中提供的輸液溶液或注射溶液。

如果被測(cè)單元中存在的尺寸等于或大于10 µm的顆粒平均數(shù)不超過(guò)3000個(gè)/容器，且尺寸大于等于25 um的顆粒平均數(shù)不超過(guò)300個(gè)/容器，則制劑符合試驗(yàn)要求。

檢測(cè)結(jié)果判定標(biāo)準(zhǔn)總結(jié)：