JP2022504397A - 低pHウイルス不活化のための新しい連続フロー反応器 - Google Patents
低pHウイルス不活化のための新しい連続フロー反応器 Download PDFInfo
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Abstract
Description
実施例
実施例1-計算流体力学
結果の例
流れ動力学の結果
滞留時間分布(RTD)の結果
、この式で表されたF曲線(累積分布曲線)が0.005に等しい(F0.005)時間として近似される。実験モデルとCFDモデルとに関する無次元E曲線が、比較のために、図6(a)(b)に示されるように、50及び100ml/分(Reは187.7及び375.5)で夫々プロットされた。経験的データは、各流量に対して3回の実験の結果を平均することによって生成された。
JIBにおける圧力損失の結果
スケーリング結果
実施例からの結論
Claims (24)
- ウイルス不活化装置であって、
入口、出口、及び前記入口と前記出口との間に蛇行パターンを形成する交互交代する曲がり部の組を備えた管状流路を含む、少なくとも1つの連続ウイルス不活化反応器、
を備えている、
上記装置。 - 前記少なくとも1つの連続ウイルス不活化反応器は、インライン管状連続ウイルス不活化反応器である、請求項1に記載の装置。
- 前記交互交代する曲がり部の組は、約270°~約280°の角度を有する少なくとも2つの交互交代する曲がり部を含む、請求項1に記載の装置。
- 前記交互交代する曲がり部の組は、約270°~約280°の角度を有する約2~約325ターンの交互交代する曲がり部を含む、請求項1に記載の装置。
- 前記管状流路は、約0.6cm~約0.7cmの直径を含む、請求項1に記載の装置。
- 前記交互交代する曲がり部の組は、少なくとも2つの積み重ねられた層に垂直に分割されている、請求項1に記載の装置。
- 前記少なくとも2つの積み重ねられた層の各々は、単一面内に12.5の交互交代する曲がり部を含み、前記交互交代する曲がり部の各々は、約270°~約280°の角度を含む、請求項6に記載の装置。
- 前記少なくとも2つの積み重ねられた層の各々は、約0.7cm~約1.2cmの厚さを含む、請求項6に記載の装置。
- 前記少なくとも2つの積み重ねられた層の各々は、前記管状流路の1つの180°曲がり部を介して互いに接続されている、請求項6に記載の装置。
- 前記少なくとも2つの積み重ねられた層は、前記管状流路の25個の180°曲がり部を介して互いに接続された26層である、請求項9に記載の装置。
- 前記少なくとも1つの連続ウイルス不活化反応器は、直列に接続された約2~約6のウイルス不活化反応器を含む、請求項1に記載の装置。
- 前記交互交代する曲がり部の組は、渦を生成して、約187.7~約375.5のレイノルズ数を備える層流を有する生成物ストリームの混合を誘発するように配置されている、請求項1に記載の装置。
- 前記管状流路は、生成物ストリームが少なくとも30分間、前記連続ウイルス不活化反応器内にあるように寸法を取られている、請求項1に記載の装置。
- ウイルス不活化装置であって、
第1の静的混合器と流体連絡する入口と、第2の静的混合器と流体連絡する出口とを有する低pH連続ウイルス不活化反応器、
を含み、
ここで、前記低pH連続ウイルス不活化反応器は、交互交代する曲がり部の組で形成された管を含んでいる、
上記装置。 - 前記管は、生成物ストリームが少なくとも30分間、低pH連続ウイルス不活化反応器内にあるように寸法を取られている、請求項14に記載の装置。
- 前記交互交代する曲がり部の組における各曲がり部が、約270°~約280°までの角度を含む、請求項14に記載の装置。
- 前記交互交代する曲がり部の組は、約0.85cm~約2cmの曲率半径を含む、請求項14に記載の装置。
- 前記管は、325ターンの交互交代する曲がり部を含む、請求項14に記載の装置。
- 前記管は、25個の管状流路であって、その各々が1つの180°曲がり部を有しているものによって、互いに接続された26層の垂直層に分割されている、請求項14に記載の装置。
- 前記管は、少なくとも12.5回の交互交代する曲がり部を単一の面内に含んでいる、請求項14に記載の装置。
- 前記低pH連続ウイルス不活化反応器は、直列に接続された約2~約6のウイルス不活化反応器を含んでいる、請求項14に記載の装置。
- 生成物ストリームの連続低pHウイルス不活化のための方法であって、
前記生成物ストリームを、そのpHを所定のウイルス不活化pHにまで下げるために、第1の静的混合器に導入すること、
不活性化されるために前記第1の静的混合器を出る前記生成物ストリームを、単一面内に複数の曲がり部の組を有する管の入口に導入すること、
前記生成物ストリームをウイルス不活化条件下で前記管を通して流すこと、及び
前記生成物ストリームを前記管の出口を通して前記管から出すこと、
を包含し、
ここで、前記生成物ストリームの前記pHを下げるために、低pH緩衝液が前記第1の静的混合器に導入される、
上記方法。 - 単一面内の前記複数の曲がり部は、蛇行パターンを形成している、請求項22に記載の方法。
- 前記生成物ストリームは、プロテインA捕捉器から第1の静的混合器に導入される、請求項22に記載の方法。
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PCT/US2019/054959 WO2020076681A1 (en) | 2018-10-08 | 2019-10-07 | A novel continuous flow reactor for low ph viral inactivation |
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CN (1) | CN113015787A (ja) |
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CA (1) | CA3115253A1 (ja) |
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EP3864130A1 (en) * | 2018-10-08 | 2021-08-18 | Boehringer Ingelheim International GmbH | A system and method to determine critical process parameters for a continuous viral inactivation reactor to design and manufacture same |
WO2021222735A1 (en) * | 2020-04-30 | 2021-11-04 | Massachusetts Institute Of Technology | Model-based control for column-based continuous viral inactivation of biopharmaceuticals |
WO2021257387A1 (en) * | 2020-06-16 | 2021-12-23 | Boehringer Ingelheim International Gmbh | A method of providing a homogeneous feed stream within a plug flow reactor |
MX2023005058A (es) * | 2020-11-09 | 2023-05-12 | Amgen Inc | Verificacion en proceso del estado de calibracion de las sondas de ph. |
DE102021107394A1 (de) * | 2021-03-24 | 2022-09-29 | Sartorius Stedim Biotech Gmbh | Vorrichtung zur kontinuierlichen Vireninaktivierung |
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WO2016173982A1 (de) * | 2015-04-28 | 2016-11-03 | Bayer Technology Services Gmbh | Verfahren zur kontinuierlichen virusinaktivierung in einem mikroreaktor |
US20160375159A1 (en) * | 2014-03-11 | 2016-12-29 | Bayer Aktiengesellschaft | Device and method for continuous virus inactivation |
WO2017156355A1 (en) * | 2016-03-11 | 2017-09-14 | Boehringer Ingelheim International Gmbh | Methods for continuously inactivating a virus during manufacture of a protein |
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DK3131589T3 (da) * | 2014-04-15 | 2023-08-07 | Boehringer Ingelheim Int | Fremgangsmåde og anvendelse til fortløbende inaktivering af en virus under tilvejebringelse af et biologisk produkt |
EP3031518B1 (en) * | 2014-12-08 | 2021-01-20 | Lonza Ltd | Fluid mixing structure, continuous reaction unit, continuous reaction reactor and method of using the same |
EP3864130A1 (en) * | 2018-10-08 | 2021-08-18 | Boehringer Ingelheim International GmbH | A system and method to determine critical process parameters for a continuous viral inactivation reactor to design and manufacture same |
US20230064241A1 (en) * | 2020-02-03 | 2023-03-02 | Merck Patent Gmbh | Modular incubation chamber and method of virus inactivation |
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US20160375159A1 (en) * | 2014-03-11 | 2016-12-29 | Bayer Aktiengesellschaft | Device and method for continuous virus inactivation |
WO2016173982A1 (de) * | 2015-04-28 | 2016-11-03 | Bayer Technology Services Gmbh | Verfahren zur kontinuierlichen virusinaktivierung in einem mikroreaktor |
WO2017156355A1 (en) * | 2016-03-11 | 2017-09-14 | Boehringer Ingelheim International Gmbh | Methods for continuously inactivating a virus during manufacture of a protein |
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BIOTECHNOLOGY AND BIOENGINEERING, vol. Vol.115, p.606-616, JPN6022020011, March 2018 (2018-03-01), ISSN: 0005034325 * |
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WO2020076681A1 (en) | 2020-04-16 |
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