The revised harmonised general chapter "Particulate Contamination (Q-09)" was signed-off by the Pharmacopeial Discussion Group (PDG) on 2 May 2025. The PDG brings together the European Pharmacopoeia (Ph. Eur.), the Indian Pharmacopoeia Commission (IPC), the Japanese Pharmacopoeia (JP) and the United States Pharmacopeia (USP).
經(jīng)修訂的協(xié)調(diào)總論《顆粒物污染（Q-09）》于 2025 年 5 月 2 日由藥典討論組（PDG）審定通過(guò)。PDG 匯聚了歐洲藥典（Ph. Eur.）、印度藥典委員會(huì)（IPC）、日本藥典（JP）和美國(guó)藥典（USP）。
The revision of Q-09 represents a significant step forward in standardised testing procedures for sub-visible particulate matter in all injectable products applied in the PDG regions. This update makes the process more robust and adaptable to different product types, including biologicals. Major changes include:
Q-09 的修訂標(biāo)志著 PDG 區(qū)域內(nèi)所有注射劑產(chǎn)品中不溶性微粒的標(biāo)準(zhǔn)化檢測(cè)程序向前邁出重要一步。此次更新使流程更穩(wěn)健，且能適配包括生物制品在內(nèi)的不同產(chǎn)品類型。主要變化包括：
Definition clarification
定義澄清
Guidance on sample preparation, especially for formulations with a volume of 25 mL or less
樣品制備指導(dǎo)（尤其針對(duì)體積≤25 mL 的制劑）
Method 1 (light obscuration particle count test) updates
Method 2 (microscopic particle count test) updates
方法 2（顯微法顆粒計(jì)數(shù)測(cè)試）更新
These revisions ensure clear, comprehensive standards aligned with current scientific and regulatory expectations, ultimately contributing to improved drug development and public health. The well-established acceptance criteria have been kept from the previous version of the text. The full sign-off text can be found on the website. The corresponding regional texts for the harmonised general chapter on Particulate Contamination are scheduled for publication in April 2026 (JP general test <6.07>), July 2026 (Ph. Eur. general chapter 2.9.19), and July 2025 are scheduled for <788> with <787> to be omitted in the future). The IPC as newest member will sign and implement the text at a later stage according to its implementation plan for all PDG harmonised texts。
這些修訂確保了清晰、全面的標(biāo)準(zhǔn)，與當(dāng)前科學(xué)和監(jiān)管預(yù)期一致，最終助力藥物研發(fā)改進(jìn)與公共健康提升。先前版本中已確立的接受標(biāo)準(zhǔn)得以保留。完整審定文本可在官網(wǎng)查閱。顆粒物污染協(xié)調(diào)總論的對(duì)應(yīng)區(qū)域文本計(jì)劃于 2026 年 4 月（日本藥典通用測(cè)試 <6.07>）、2026 年 7 月（歐洲藥典總論 2.9.19）發(fā)布，且 2025 年 7 月計(jì)劃發(fā)布 < 788>（未來(lái) < 787 > 將被廢止）。作為最新成員的印度藥典委員會(huì)（IPC）將依據(jù)其針對(duì)所有 PDG 協(xié)調(diào)文本的實(shí)施計(jì)劃，在后續(xù)階段簽署并執(zhí)行該文本。
The PDG has successfully harmonised all the general chapters on its work programme (31) in addition to 48 of the 62 excipient monographs listed. The current work programme, including all ongoing items, is available on the website (General chapters, Excipients).
除所列 62 項(xiàng)輔料專論中的 48 項(xiàng)外，PDG 已成功協(xié)調(diào)其工作方案中的全部總論（共 31 項(xiàng)）。當(dāng)前工作方案（含所有在研項(xiàng)目）可在官網(wǎng)查閱（總論、輔料板塊）。
具體內(nèi)容如下：
PHARMACOPOEIAL DISCUSSION GROUP
藥典討論小組
SIGN-OFF DOCUMENT
簽署文件
CODE: Q-09
代碼：Q-09
NAME: PARTICULATE CONTAMINATION
名稱：顆粒物污染
REVISION 2
修訂版 2
It is understood that sign-off covers the technical content of the draft and each party will adapt it as necessary to conform to the usual presentation of the pharmacopoeia in question; such adaptation includes stipulation of the particular pharmacopoeia’s reference materials and general chapters.
各方理解，簽署行為涵蓋草案的技術(shù)內(nèi)容，且各方將根據(jù)需要對(duì)其調(diào)整，以符合所涉藥典的常規(guī)表述形式；此類調(diào)整包括規(guī)定特定藥典的標(biāo)準(zhǔn)物質(zhì)和總論。
Harmonised provisions:
協(xié)調(diào)條款：
Legend
圖例：
+ will adopt and implement; − will not stipulate
+表示 “將采用并實(shí)施”；− 表示 “將不規(guī)定”
Non-harmonised provisions:
非協(xié)調(diào)條款：
The requirements for preparations supplied in containers with a nominal value of 100 mL
對(duì)裝量 100 mL 容器中的制劑的要求
Local requirements
當(dāng)?shù)匾?/span>
Q-09 PARTICULATE CONTAMINATION: SUB-VISIBLE PARTICLES
Q-09 顆粒物污染：不溶性微粒
Unintended particulate matter in parenteral preparations consists of mobile undissolved substances, other than gas bubbles, that may originate from various sources such as contamination. The level of particulate matter must be minimised and controlled, independent of its type.
注射劑中的非預(yù)期顆粒物由可移動(dòng)的未溶解物質(zhì)（氣泡除外）組成，這些物質(zhì)可能來(lái)自污染等各類來(lái)源。無(wú)論顆粒物的類型如何，都必須將其含量降至最低并加以控制。
For the determination of sub-visible particulate matter 2 procedures are described hereafter: Method 1 (Light Obscuration Particle Count Test) and Method 2 (Microscopic Particle Count Test). It is preferable to use Method 1 when examining the parenteral preparation for sub-visible particles.
為測(cè)定不溶性微粒，以下闡述兩種方法：方法 1（光阻法顆粒計(jì)數(shù)試驗(yàn)）和方法 2（顯微法顆粒計(jì)數(shù)試驗(yàn)）。檢查注射劑中的不溶性微粒時(shí)，優(yōu)先采用方法 1。
However, not all parenteral preparations can be examined directly 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 (some emulsions, suspensions, colloids, and liposomal preparations are examples), the test is carried out according to Method 2. Similarly, specific precautions may be required for preparations that produce air or gas bubbles when drawn into the sensor. If the viscosity of the preparation to be tested precludes its examination by either procedure, a quantitative dilution with an appropriate particle-free diluent may be made to decrease viscosity to a value that allows the analysis to be performed.
然而，并非所有注射劑都能通過(guò)這一種或兩種方法直接檢測(cè)不溶性微粒。當(dāng)方法 1 不適用時(shí)（例如，制劑澄清度低或粘度大的情況，如某些乳劑、混懸液、膠體和脂質(zhì)體制劑），則按方法 2 進(jìn)行試驗(yàn)。同樣，對(duì)于吸入傳感器時(shí)會(huì)產(chǎn)生氣泡的制劑，可能需要采取特定的預(yù)防措施。若待測(cè)試制劑的粘度導(dǎo)致無(wú)法通過(guò)任一方法檢測(cè)，可用適當(dāng)?shù)臒o(wú)顆粒稀釋劑進(jìn)行定量稀釋，將粘度降低至允許分析的數(shù)值。
Obscuration methods measure different characteristics, the results of the Light Obscuration Particle Count Test are not equivalent to those of the Microscopic Particle Count Test and the two methods cannot be considered interchangeable.
光阻法測(cè)量的是不同特性，光阻法顆粒計(jì)數(shù)試驗(yàn)的結(jié)果與顯微法顆粒計(jì)數(shù)試驗(yàn)的結(jié)果并不等效，且這兩種方法不可視為可互換。
The results obtained when examining a discrete unit or group of units cannot be extrapolated with certainty to other units that remain untested. Thus, statistically sound sampling plans based on product and process characteristics must be developed if valid inferences are to be drawn from observed data to characterise the level of particulate matter in a large group of units.
檢測(cè)單個(gè)單元或一組單元所得的結(jié)果，無(wú)法確定地外推至未檢測(cè)的其他單元。因此，若要從觀測(cè)數(shù)據(jù)合理推斷大量單元中顆粒物的含量水平，必須制定基于產(chǎn)品和工藝特性、統(tǒng)計(jì)學(xué)的抽樣計(jì)劃。
METHOD 1. LIGHT OBSCURATION PARTICLE COUNT TEST
方法 1：光阻法顆粒計(jì)數(shù)試驗(yàn)
Use a suitable apparatus based on the principle of light blockage that allows an automatic determination of the size of particles and the number of particles according to size.
使用基于光阻原理的合適儀器，該儀器可自動(dòng)測(cè)定顆粒大小及不同粒徑的顆粒數(shù)量。
The apparatus is calibrated using suitable certified reference materials consisting of dispersions of spherical particles of known sizes at about 10 µm and 25 µm. These standard particles are dispersed in particle-free water R. Care must be taken to avoid agglomeration of particles during dispersion.
儀器需用合適的認(rèn)證標(biāo)準(zhǔn)物質(zhì)校準(zhǔn)，該標(biāo)準(zhǔn)物質(zhì)由已知粒徑（約 10 µm 和 25 µm）的球形顆粒分散液組成。這些標(biāo)準(zhǔn)顆粒分散在無(wú)顆粒水 R 中，分散過(guò)程中必須注意避免顆粒團(tuán)聚。
General precautions
一般注意事項(xiàng)
Carry out the test under conditions limiting further contamination with particles, preferably in a laminar-flow cabinet.
試驗(yàn)應(yīng)在防止進(jìn)一步顆粒污染的條件下進(jìn)行，優(yōu)先選擇在層流操作柜中操作。
Very carefully wash glassware and the equipment used in the test procedure by cleaning with a warm detergent solution and rinsing with abundant amounts of water to remove all traces of detergent. Immediately before use, rinse the fluid path with particle-free water R.
需非常仔細(xì)地清洗試驗(yàn)所用的玻璃器皿和設(shè)備：先用溫?zé)岬南礈靹┤芤呵逑矗儆么罅克疀_洗以除去所有洗滌劑殘留。使用前立即用無(wú)顆粒水 R 沖洗流體通路。
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測(cè)的制劑中，尤其在將制劑分取轉(zhuǎn)移至測(cè)定用容器時(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, carry out the following test: determine the particle count in 5 aliquots of 5 mL of particle-free water R or an alternative particle-free diluent if justified, each of degassed 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.
為檢查環(huán)境是否適合試驗(yàn)、玻璃器皿是否清洗干凈以及所用的水是否無(wú)顆粒，需進(jìn)行以下試驗(yàn)：取 5 份 5 mL 的無(wú)顆粒水 R（如有正當(dāng)理由，可使用其他無(wú)顆粒稀釋劑），每份按以下方法脫氣，測(cè)定其中的顆粒數(shù)。若合并 25 mL 中粒徑≥10 µm 的顆粒數(shù)超過(guò) 25，則試驗(yàn)采取的預(yù)防措施不足，必須重復(fù)準(zhǔn)備步驟，直至環(huán)境、玻璃器皿和水都適合試驗(yàn)。
Method
方法
Clean the outer surfaces of the container(s) using a jet of particle-free water R and avoid contamination of the contents. Samples are tested in a manner that most closely represents the product use. For parenteral preparations that have a sufficient volume for a single test, test individual units to estimate the level and variation of particulate matter in an entire group of units.
用無(wú)顆粒水 R 清洗容器外表面，避免污染內(nèi)容物。樣品的測(cè)試方式應(yīng)盡可能接近產(chǎn)品的使用方式。對(duì)于單份試驗(yàn)體積足夠的注射劑，測(cè)試單個(gè)單元以估計(jì)整組單元中顆粒物的含量水平和變異性。
For parenteral preparations that do not have a sufficient volume for a single test, carefully and thoroughly mix each unit. Then combine the contents of a suitable number of units in a separate container, to obtain the volume required for a single test, based on instrument capability and properties of the sample.
對(duì)于單份試驗(yàn)體積不足的注射劑，需仔細(xì)并充分混合每個(gè)單元，然后將適量數(shù)量單元的內(nèi)容物合并到單獨(dú)的容器中，根據(jù)儀器性能和樣品特性，獲得單份試驗(yàn)所需的體積。
Powers for injections and infusions are reconstituted with particle-free water R or an alternative particle-free diluent when particle-free water R is not suitable.
注射用粉末和輸液劑如需復(fù)溶，若無(wú)顆粒水 R 不適用，則用無(wú)顆粒水 R 或其他合適的無(wú)顆粒稀釋劑復(fù)溶。
Eliminate gas bubbles by appropriate measures such as allowing to stand, applying a gentle vacuum, or sonicating. Preparations containing proteins should not be sonicated. After sample treatment, the sample should be remixed gently but thoroughly to suspend the particles, taking care to minimize the generation of bubbles.
通過(guò)靜置、施加輕微真空或超聲等適當(dāng)措施除去氣泡，含蛋白質(zhì)的制劑不得超聲。樣品處理后，應(yīng)輕輕但充分地重新混合樣品以懸浮顆粒，注意盡量減少氣泡產(chǎn)生。
The number of test samples must be adequate to provide a statistically sound assessment. For large and small volume parenterals, an adequate volume of test sample must be provided for analysis; however, single units may be tested in a statistically sound sampling plan.
測(cè)試樣品的數(shù)量必須足夠，以提供統(tǒng)計(jì)學(xué)上可靠的評(píng)估。對(duì)于大容量和小容量注射劑，必須提供足夠體積的測(cè)試樣品用于分析；不過(guò)，單個(gè)單元可在統(tǒng)計(jì)學(xué)合理的抽樣計(jì)劃中進(jìn)行測(cè)試。
Remove 4 portions, each of approximately 5 mL, and count the number of particles equal to or larger than 10 µm and 25 µm. Disregard the result obtained from the first portion and calculate the average number of particles from the remaining portions of the preparation to be examined. The number of particles per unit is calculated from the number of particles per volume. Volumes smaller than 5 mL can also be tested provided that this amount is appropriately justified. In general, for parenteral products that do not have a sufficient volume (e.g. less than 25 mL), it may be acceptable to carry out the test with a volume of 1 to 5 mL.
移取 4 份，每份約 5 mL，計(jì)數(shù)粒徑≥10 µm 和≥25 µm 的顆粒數(shù)。舍去第一份的結(jié)果，從待檢測(cè)制劑的剩余份中計(jì)算顆粒數(shù)的平均值。每單位的顆粒數(shù)由單位體積的顆粒數(shù)計(jì)算得出。如經(jīng)論證，也可測(cè)試小于 5 mL 的體積。一般而言，對(duì)于體積不足的注射劑（如小于 25 mL），使用 1 至 5 mL 的體積進(jìn)行試驗(yàn)可能是可接受的。
Evaluation
評(píng)估
For preparations supplied in units that contain a nominal volume of more than 100 mL, apply the criteria of test 1.A.
對(duì)于以單位包裝供應(yīng)、標(biāo)稱體積大于 100 mL 的制劑，采用試驗(yàn) 1.A 的判定標(biāo)準(zhǔn)。
For preparations supplied in units that contain a nominal volume of less than 100 mL, apply the criteria of test 1.B.
對(duì)于以單位包裝供應(yīng)、標(biāo)稱體積小于 100 mL 的制劑，采用試驗(yàn) 1.B 的判定標(biāo)準(zhǔn)。
For preparations supplied in units that contain a nominal volume of 100 mL, apply the criteria of test 1.A (JP requirements) or those of test 1.B (Ph. Eur. and USP requirements).
對(duì)于以單位包裝供應(yīng)、標(biāo)稱體積為 100 mL 的制劑，采用試驗(yàn) 1.A 的標(biāo)準(zhǔn)（日本藥典要求）或試驗(yàn) 1.B 的標(biāo)準(zhǔn)（歐洲藥典和美國(guó)藥典要求）。
If the number of particles in a tested unit exceeds the limits, test the preparation by the microscopic particle count test.
若被測(cè)單元中的顆粒數(shù)超過(guò)限值，則采用顯微顆粒計(jì)數(shù)試驗(yàn)檢測(cè)該制劑。
Test 1.A – Preparations for infusion or injection supplied in units that contain a nominal content of more than 100 mL
試驗(yàn) 1.A—— 單位包裝標(biāo)稱體積超過(guò) 100 mL 的輸液或注射劑
The preparation complies with the test if, in each unit tested, the number of particles present per unit that are 10 µm or larger in size does not exceed 25 per millilitre and the number of particles that are 25 µm or larger in size does not exceed 3 per millilitre.
若每個(gè)被測(cè)單元中，粒徑≥10 µm 的顆粒數(shù)每毫升不超過(guò) 25 個(gè)，且粒徑≥25 µm 的顆粒數(shù)每毫升不超過(guò) 3 個(gè)，則該制劑符合試驗(yàn)要求。
Test 1.B – Preparations for infusion or injection supplied in units that contain a nominal content of less than 100 mL
試驗(yàn) 1.B—— 單位包裝標(biāo)稱體積小于 100 mL 的輸液或注射劑
The preparation complies with the test if, in each unit tested, the number of particles present per unit that are 10 µm or larger in size does not exceed 6000 per container and the number of particles that are 25 µm or larger in size does not exceed 600 per container. Where combining units is required, the average number of particles present in the combined sample is used to calculate the number of particles in one container.
若每個(gè)被測(cè)單元中，粒徑≥10 µm 的顆粒數(shù)每容器不超過(guò) 6000 個(gè)，且粒徑≥25 µm 的顆粒數(shù)每容器不超過(guò) 600 個(gè)，則該制劑符合試驗(yàn)要求。若需合并單元，以合并樣品中的平均顆粒數(shù)計(jì)算單個(gè)容器中的顆粒數(shù)。
When justified and authorized for example in cases of highly viscous preparations, dilution of samples may be required to obtain reliable results. Dilution is allowed provided that the diluent and methods are demonstrated to be appropriate and the smallest level of dilution that allows for reproducible testing is used.
當(dāng)經(jīng)論證并經(jīng)批準(zhǔn)時(shí)，可能需稀釋樣品（如針對(duì)高粘度制劑）以獲得可靠結(jié)果。在證明稀釋劑和方法適用，且采用能實(shí)現(xiàn)可重復(fù)測(cè)試的最小稀釋度的情況下，則允許稀釋。
METHOD 2. MICROSCOPIC PARTICLE COUNT TEST
方法 2. 顯微顆粒計(jì)數(shù)試驗(yàn)
Use a suitable binocular microscope and a filter assembly to retain particulate matter on a membrane filter.
使用合適的雙目顯微鏡和濾器組件，將顆粒物截留到膜濾器上。
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, a suitable illuminator to provide episcopic illumination in addition to oblique illumination, and its diameter grade to 100 (see Figure 1).
顯微鏡配備經(jīng)物鏡測(cè)微尺校準(zhǔn)的目鏡測(cè)微尺、可固定并遍歷膜濾器整個(gè)過(guò)濾區(qū)域的機(jī)械載物臺(tái)、除斜射照明外還能提供落射照明的合適照明裝置，且其直徑規(guī)格為 100（見圖 1）。
The ocular micrometer is a circular diameter graticule (100 magnifications) and consists of a large circle divided by crosshairs into quadrants, transparent scale graduated circles 10 µm and 25 µm in diameter at 100 magnifications, and a linear black reference 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 its linear scale of the graticule within 2 per cent is acceptable. The large circle is designated the graticule field of view (FOV).
目鏡測(cè)微尺為圓形直徑分劃板（100 倍放大），由十字線劃分為象限的大圓圈、100 倍放大下直徑為 10 µm 和 25 µm 的透明刻度圓圈，以及 10 µm 增量的黑色線性參考線組成。它需用經(jīng)國(guó)內(nèi)或國(guó)際標(biāo)準(zhǔn)機(jī)構(gòu)認(rèn)證的載物臺(tái)測(cè)微尺校準(zhǔn)，分劃板線性刻度相對(duì)誤差在 2% 以內(nèi)可接受。大圓圈指定為分劃板視野（FOV）。
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°.
需配備兩種照明裝置：一種是顯微鏡內(nèi)置的落射明場(chǎng)照明器，另一種是外置、可聚焦的輔助照明器，可調(diào)節(jié)至 10 - 20° 角提供反射斜射照明。
The filter assembly consists of a filter holder made of glass or other suitable material,
濾器組件包括由玻璃或其他合適材料制成的濾器支架，
and is equipped with a vacuum source and a suitable membrane filter.
并配備真空源和合適的膜濾器。
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.
膜濾器尺寸合適，顏色為黑色或深灰色，可為無(wú)網(wǎng)格或有網(wǎng)格，標(biāo)稱孔徑為 1.0 µm 或更細(xì)。
General precautions
一般注意事項(xiàng)
Carry out the test under conditions limiting further contamination with particles, preferably in a laminar-flow cabinet.
在防止進(jìn)一步顆粒污染的條件下進(jìn)行試驗(yàn)，優(yōu)先選擇在層流操作柜中進(jìn)行。
Very carefully wash the glassware and filtration 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.
除膜濾器外，需非常仔細(xì)地用溫?zé)嵯礈靹┤芤呵逑此貌Ａ髅蠛瓦^(guò)濾組件，再用大量水沖洗以除去所有洗滌劑殘留。使用前立即用無(wú)顆粒水 R 沖洗膜濾器兩面及設(shè)備（先外后內(nèi)、從上到下）。
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, carry out the following test: determine the level of particulate matter of a 50-mL volume of particle-free water R following the procedure described below. If more than 20 particles 10 µm or larger in size or, if more than 3 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.
為核查環(huán)境是否適用于試驗(yàn)、玻璃器皿和膜濾器是否清洗合格，以及所用的水是否無(wú)顆粒，需進(jìn)行以下試驗(yàn)：按下述步驟測(cè)定 50 mL 無(wú)顆粒水 R 中的顆粒物水平。若過(guò)濾區(qū)域內(nèi)粒徑≥10 µm 的顆粒數(shù)超過(guò) 20 個(gè)，或粒徑≥25 µm 的顆粒數(shù)超過(guò) 3 個(gè)，則試驗(yàn)采取的防護(hù)措施不足。必須重復(fù)準(zhǔn)備步驟，直至環(huán)境、玻璃器皿、膜濾器和水均滿足試驗(yàn)要求。
Method
方法
Clean the outer surfaces of the container(s) using a jet of particle-free water R and avoid contamination of the contents. Samples are tested in a manner that most closely represents the product use. For parenteral preparations that have a sufficient volume for a single test, testing of individual units is often preferred to estimate the level and variation of particulate matter in an entire group of units.
用無(wú)顆粒水 R 噴射清洗容器外表面，避免污染內(nèi)容物。樣品測(cè)試方式應(yīng)盡可能貼近產(chǎn)品實(shí)際使用情況。對(duì)于單份試驗(yàn)體積足夠的注射劑，通常優(yōu)先測(cè)試單個(gè)單元，以估算整組單元中顆粒物的含量水平及變異情況。
For parenteral preparations that do not have a sufficient volume for a single test, carefully and thoroughly mix each unit. Then combine the contents of a suitable number of units in a separate container to obtain the volume required for a single test based on instrument capability and properties of the sample.
對(duì)于單份試驗(yàn)體積不足的注射劑，需仔細(xì)充分混合每個(gè)單元，再將適量單元的內(nèi)容物合并到單獨(dú)容器中，根據(jù)儀器性能和樣品特性，獲取單份試驗(yàn)所需體積。
Lyophilized solids or powders for injections and infusions are reconstituted with particle-free water R or an alternative particle-free diluent when particle-free water R is not suitable.
注射用凍干固體、粉末及輸液劑如需復(fù)溶，若無(wú)顆粒水 R 不適用，可用無(wú)顆粒水 R 或其他合適的無(wú)顆粒稀釋劑復(fù)溶。
The number of test samples must be adequate to provide a statistically sound assessment. For large and small volume parenterals, an adequate volume of sample must be provided for analysis; however, single units may be tested in a statistically sound sampling plan.
測(cè)試樣品數(shù)量需足夠，以提供統(tǒng)計(jì)學(xué)上可靠的評(píng)估。對(duì)于大、小體積注射劑，均需提供足夠體積的樣品用于分析；不過(guò)，單個(gè)單元可在統(tǒng)計(jì)學(xué)合理的抽樣計(jì)劃中測(cè)試。
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 sample pool or a single unit and apply vacuum. If needed, add last portion, rinse the inner unit or the entire volume is filtered. After adding the sample a portion of 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 larger than 10 µm and 25 µm. Determine the number of particles per unit. Where particle distribution on the filter is uniform, partial filter count and determination of the total filter count by calculation is allowed.
用幾毫升無(wú)顆粒水 R 潤(rùn)濕裝有膜濾器的濾器支架內(nèi)部。將樣品池的全部體積或單個(gè)單元轉(zhuǎn)移至過(guò)濾漏斗，施加真空。若有需要，添加最后一部分，沖洗內(nèi)部單元或過(guò)濾全部體積。加入樣品后，用無(wú)顆粒水 R 噴射沖洗濾器支架內(nèi)壁。保持真空直至膜濾器表面無(wú)液體。將濾器放入培養(yǎng)皿，使蓋子微開，讓濾器風(fēng)干。濾器干燥后，將培養(yǎng)皿置于顯微鏡載物臺(tái)，在反射光下掃描整個(gè)膜濾器，計(jì)數(shù)粒徑≥10 µm 和≥25 µm 的顆粒，測(cè)定每單元的顆粒數(shù)。若顆粒在濾器上分布均勻，允許對(duì)濾器部分區(qū)域計(jì)數(shù)并通過(guò)計(jì)算確定濾器總顆粒數(shù)。
The performing mental process with the use of the circular diameter graticule is carried out by transforming sizably 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. For elongated fibers size should be assigned based on the longest dimension
使用圓形直徑分劃板時(shí)，操作過(guò)程為：將每個(gè)顆粒的圖像大致轉(zhuǎn)化為圓形，再與 10 µm 和 25 µm 的分劃板參考圓對(duì)比。在此過(guò)程中，顆粒不會(huì)從其在分劃板視野內(nèi)的初始位置移動(dòng)，也不會(huì)疊加在參考圓上進(jìn)行對(duì)比。透明分劃板參考圓的內(nèi)徑用于測(cè)定白色和透明顆粒的大小，深色顆粒則通過(guò)黑色不透明分劃板參考圓的外徑測(cè)定大小。對(duì)于細(xì)長(zhǎng)纖維，應(yīng)根據(jù)其最長(zhǎng)維度確定尺寸。
In performing the microscopic particle count test care should be taken to ensure that individual particles are discernible. Do not attempt to size or enumerate amorphous, semi-liquid, or otherwise morphologically indistinct materials that are flat, show little or no stain or observation on the membrane filter. These materials have the appearance film-like relief, no shadow when illuminated from the side, and present a gelatinous or no surface aspect (for instance protein or fatty acid particles). In such cases, the interpretation of enumeration may be aided by testing a sample of the preparation by the light obscuration particle count test.
進(jìn)行顯微顆粒計(jì)數(shù)試驗(yàn)時(shí)，應(yīng)注意確保單個(gè)顆粒可辨別。切勿嘗試測(cè)定或計(jì)數(shù)膜濾器上那些無(wú)定形、半液體或其他形態(tài)模糊的物質(zhì)（這類物質(zhì)扁平、染色淺或不染色）。此類物質(zhì)外觀呈膜狀浮雕，側(cè)面照射時(shí)無(wú)陰影，表面無(wú)膠狀或其他特征（如蛋白質(zhì)或脂肪酸顆粒）。在此類情況下，可通過(guò)光阻法顆粒計(jì)數(shù)試驗(yàn)測(cè)試制劑樣品，輔助判斷計(jì)數(shù)結(jié)果。
Evaluation
評(píng)估
For preparations supplied in units that contain a nominal volume of more than 100 mL, apply the criteria of test 2.A.
對(duì)于以單位包裝供應(yīng)、標(biāo)稱體積超過(guò) 100 mL 的制劑，采用試驗(yàn) 2.A 的判定標(biāo)準(zhǔn)。
For preparations supplied in units that contain a nominal volume of less than 100 mL, apply the criteria of test 2.B.
對(duì)于以單位包裝供應(yīng)、標(biāo)稱體積小于 100 mL 的制劑，采用試驗(yàn) 2.B 的判定標(biāo)準(zhǔn)。
For preparations supplied in units that contain a nominal volume of 100 mL, apply the criteria of test 2.A (JP requirements) or those of test 2.B (Ph. Eur. and USP requirements).
對(duì)于以單位包裝供應(yīng)、標(biāo)稱體積為 100 mL 的制劑，采用試驗(yàn) 2.A 的標(biāo)準(zhǔn)（日本藥典要求）或試驗(yàn) 2.B 的標(biāo)準(zhǔn)（歐洲藥典和美國(guó)藥典要求）。
Test 2.A – Preparations for infusion or injection supplied in units that contain a nominal content of more than 100 mL
試驗(yàn) 2.A—— 單位包裝標(biāo)稱體積超過(guò) 100 mL 的輸液或注射劑
The preparation complies with the test if, in each unit tested, the number of particles present per unit that are 10 µm or larger in size does not exceed 12 per millilitre and the number of particles that are 25 µm or larger in size does not exceed 2 per millilitre.
若每個(gè)被測(cè)單元中，粒徑≥10 µm 的顆粒數(shù)每毫升不超過(guò) 12 個(gè)，且粒徑≥25 µm 的顆粒數(shù)每毫升不超過(guò) 2 個(gè)，則該制劑符合試驗(yàn)要求。
Test 2.B – Preparations for infusion or injection supplied in units that contain a nominal content of less than 100 mL
試驗(yàn) 2.B—— 單位包裝標(biāo)稱體積小于 100 mL 的輸液或注射劑
The preparation complies with the test if, in each unit tested, the number of particles present per unit that are 10 µm or larger in size does not exceed 3000 per container and the number of particles that are 25 µm or larger in size does not exceed 300 per container. Where combining units is required, the average number of particles present in the combined sample is used to calculate the number of particles in one container.
若每個(gè)被測(cè)單元中，粒徑≥10 µm 的顆粒數(shù)每容器不超過(guò) 3000 個(gè)，且粒徑≥25 µm 的顆粒數(shù)每容器不超過(guò) 300 個(gè)，則該制劑符合試驗(yàn)要求。若需合并單元，以合并樣品中的平均顆粒數(shù)計(jì)算單個(gè)容器中的顆粒數(shù)。
