藥企如何合規(guī)地應(yīng)用一次性生產(chǎn)工藝和使用一次性設(shè)備

年度

機(jī)構(gòu)

聚焦問(wèn)題

題目

2008

PQRI

吸入藥物

Best  Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug  Products: An Overview of the PQRI Recommendations

2008

BPSA

一次性產(chǎn)品

Recommendations  for Extractables and Leachables Testing

2010

BPSA

一次性產(chǎn)品

Recommendations  for Testing and Evaluation of Extractables from Single-Use Process Equipment

2014

BPOG

一次性產(chǎn)品

Standardized  Extractables Testing Protocol for Single-Use Systems in Biomanufacturing

2016

USP

塑料包裝

USP  <661>: Plastic Packaging Systems and Their Materials of Construction

Storage, mixing, or bioreactor bags and films

儲(chǔ)液、攪拌、一次性生物反應(yīng)器

1.Use a bag of size  sufficient to provide an adequate volume of extract for analysis but ≤ 5L

2.Record the volume  of the bag

3.Fill the bag with  a volume of solvent sufficient to maintain 6:1 (cm2/mL) surface area to  volume (SA/V) ratio

4.Place on an  orbital or rocker shaker at a minimum of 50 rpma for the test time period

5.Record the  solvent and concentration used, extraction time, and temperature (Table B)

6.Express  analytical results in μg/cm2

Note: Studies  performed on 2D bags of same materials can represent other bag designs, e.g.,  3D bags

Tubing

管路

1.Use a sufficient  length of ½” ID (inner diameter) tubing to provide an adequate volume of  extract for analysis

2.Record the total  length and ID of tubing

3.Fill the tubing  with a volume of solvent sufficient to maintain 6:1 (cm2/mL) SA/V ratio

4.Use pinch clamps  (or equivalent) to close the ends

5.Place on orbital  shaker at a minimum of 50 rpm for the test time period

6.Record solvent  and concentration used, extraction time, and temperature (Table B)

7.Express  analytical results in μg/cm and μg/cm2

Tubing connectors or disconnectors

管路連接和斷開(kāi)器

1.Use a sufficient  number of ½’’ ID connectors or disconnectors to provide adequate volume of extract  for analysis

2.Record length and  ID of each connector

3.Submerge in a  volume of solvent sufficient to maintain 6:1 (cm2/mL) SA/V ratio

4.Place on orbital  shaker at a minimum of 50 rpm for the test time period

5.Record the  solvent and concentration used, extraction time, and temperature (Table B)

6.Express  analytical results in μg/cm2 and μg/unit

Aseptic connectors or disconnectors

無(wú)菌連接接頭或斷開(kāi)器

1.Use a sufficient  number of ½’’ ID connectors or disconnectors to provide an adequate volume of  extract for analysis

2.Multiple  connectors can be used and extracts pooled for analysis

3.Record the length  and ID of each connector

4.Fill the  connectors or disconnectors with a volume of solvent sufficient to maintain  6:1 (cm2/mL) SA/V ratio

5.Use PTFE caps (or  equivalent inert materials) to close ends of connectors or disconnectors

6.Place on an  orbital shaker at a minimum of 50 rpm for the test time period

7.Record the  solvent and concentration used, extraction time, and temperature (Table B)

8.Express analytical  results in μg/cm2 and μg/unit

Sterilizing-grade and process filters

無(wú)菌級(jí)別濾器

1.Use filters with  Effective Filtration Area (EFA) ≥0.1 m2

2.Record the EFA of  filter

3.Recirculate or  fill with a volume of solvent sufficient to maintain 1:1 (cm2/mL) EFA to  volume ratio

4.If the solvent is  not recirculated through the filter, place the filter filled with test  solvent on an orbital shaker at a minimum of 50 rpm for the test time period  Record the solvent and concentration used, extraction time, and temperature  (Table B)

5.Express  analytical results in μg/cm2 of EFA and μg/unit

Tangential-flow Filtration Cassettes

切向流過(guò)濾系統(tǒng)

1.Use  cassettes with an EFA ≥ 0.1 m2

2.Record EFA  of cassette

3.Recirculate  volume of solvent sufficient to maintain 1:1 (cm2/mL) EFA to  volume ratio

4.Any required  preflush, sanitization, or flush steps should be performed prior to  extraction

5.Record  solvent and concentration used, extraction time, and temperature (Table B)

6.Express  analytical results in μg/cm2 of EFA and μg/unit

Sensors or Valves

檢測(cè)器或閥門(mén)

1.Use a sufficient  number of ½" ID sensors or valves to  provide an adequate volume of extract for analysis

2.Multiple  sensors or valves can be used and extracts pooled for analytical purpose

3.Record the  total surface area as the sum of tube and functional sensor surfaces for  sensors; record the total surface area as the sum of valve diaphragm and tube  surfaces for valves

4.Fill the  sensor set or valve with a volume of solvent sufficient to maintain 6:1 (cm2/mL) SA/V  ratio or closest possible SA/V ratio

5.Use PTFE  caps (or equivalent inert material) to close ends of tubes of sensor or valve  

6.Place on an  orbital shaker at a minimum of 50 rpm for the test time period

7.Record the  solvent and concentration used, extraction time, and temperature (Table B)

8.Express  analytical results in μg/sensor or μg/valve, and  μg/cm2

Chromatography  Columns or Molded Parts of Mixers or Elastomeric Parts (gaskets, O-rings, diaphragms, and septum) or  Wetted Polymeric Surfaces of Positive Displacement Pumps

層析柱或焊接部件或橡膠部件（墊圈、O型圈、隔膜）或浸潤(rùn)條件的聚合物表面或容積泵

1.Use a  sufficient size of coupon representing the finished column or molded parts of  the mixer or elastomeric parts (gaskets, O-rings, diaphragms, and septum) to  provide an adequate volume of extract for analysis

2.Record the  total surface area of the coupon

3.Submerge the  coupon in a volume of solvent sufficient to maintain 6:1 (cm2/mL) SA/V  ratio

4.Place on an  orbital shaker at a minimum of 50 rpm for the test time period

5.Record the  solvent and concentration used, extraction time, and temperature (Table B)

6.Express analytical  results in μg/cm2

Filling Needles

灌裝枕頭

1.Use needles  with smallest ID available

2.Record the  inner diameter and total surface area of the needle

3.Submerge  needles in a volume of solvent sufficient to maintain 6:1 (cm2/mL) SA/V  ratio or closest possible SA/V ratio

4.Place on an  orbital shaker at a minimum of 50 rpm for the test time period

5.Record the  solvent and concentration used, extraction time, and temperature (Table B)

6.Express  analytical results in μg/cm2

Abbreviation:  rpm = revolutions per minute or rocks per minute a 50 rpm at 20  mm radius