Process steps for the fractionation of immunoglobulin (Ig) G depleted of IgA, isoagglutinins, and devoid of in vitro thrombogenicity
BACKGROUND: Plasma-derived immunoglobulins (IgG) are essential medicines that are in worldwide shortage, especially in low- and middle-income countries. Optimised manufacturing processes can increase supply. We evaluated various new process steps for IgG fractionation.
MATERIAL AND METHODS: A crude, worst-case, IgG intermediate obtained by caprylic acid fractionation of cryoprecipitate-poor plasma was used as starting experimental material. It was processed inline by Fractogel® (Merck) TMAE anion-exchanger to deplete IgA and IgM, Eshmuno® P (Merck) anti-A and anti-B affinity chromatography to remove anti-A and anti-B isoagglutinins, 0.3% TnBP-1% Triton X-100 (S/D) treatment, C18 chromatography for removal of S/D agents, and single-pass tangential flow filtration (SPTFF) concentration to 20%. Quality, safety, and recovery were evaluated at small and pilot scales to assess purity, removal of IgA, IgM isoagglutinins, S/D agents, thrombogenic factors, and lack of toxicity in a cell model.
RESULTS: The starting IgG intermediate contained approximately 90% IgG, IgA, and IgM and 10% albumin. Fractogel® TMAE, equilibrated in 25 mM sodium acetate-pH 6.0 and loaded with up to 225 mg of IgG/mL, could remove IgA and IgM, with over 94% IgG recovery with preserved sub-class distribution in the flow-through. Sequential Eshmuno®-P anti-A and anti-B columns efficiently removed isoagglutinins. The C18 packing, used at up to 17 mL of S/D-IgG solution per mL, removed TnBP and Triton X-100 to less than 1 and 2 ppm, respectively. The 20% purified IgG was devoid of activated factor XI and thrombin generation activity.
DISCUSSION: This purification sequence yields a >99% pure, 20% (v/v) IgG product, depleted of IgA, isoagglutinins, and thrombogenic markers, and should be implementable on various IgG intermediates to help improve the supply of immunoglobulins.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
|---|---|
| Enthalten in: |
Blood transfusion = Trasfusione del sangue - 19(2021), 6 vom: 02. Nov., Seite 467-478 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Cheng, Josephine H [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Immunoglobulin A |
|---|
| Anmerkungen: |
Date Completed 17.01.2022 Date Revised 17.01.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.2450/2021.0159-21 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM329140310 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM329140310 | ||
| 003 | DE-627 | ||
| 005 | 20231225204451.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.2450/2021.0159-21 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1097.xml |
| 035 | |a (DE-627)NLM329140310 | ||
| 035 | |a (NLM)34369872 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Cheng, Josephine H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Process steps for the fractionation of immunoglobulin (Ig) G depleted of IgA, isoagglutinins, and devoid of in vitro thrombogenicity |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 17.01.2022 | ||
| 500 | |a Date Revised 17.01.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Plasma-derived immunoglobulins (IgG) are essential medicines that are in worldwide shortage, especially in low- and middle-income countries. Optimised manufacturing processes can increase supply. We evaluated various new process steps for IgG fractionation | ||
| 520 | |a MATERIAL AND METHODS: A crude, worst-case, IgG intermediate obtained by caprylic acid fractionation of cryoprecipitate-poor plasma was used as starting experimental material. It was processed inline by Fractogel® (Merck) TMAE anion-exchanger to deplete IgA and IgM, Eshmuno® P (Merck) anti-A and anti-B affinity chromatography to remove anti-A and anti-B isoagglutinins, 0.3% TnBP-1% Triton X-100 (S/D) treatment, C18 chromatography for removal of S/D agents, and single-pass tangential flow filtration (SPTFF) concentration to 20%. Quality, safety, and recovery were evaluated at small and pilot scales to assess purity, removal of IgA, IgM isoagglutinins, S/D agents, thrombogenic factors, and lack of toxicity in a cell model | ||
| 520 | |a RESULTS: The starting IgG intermediate contained approximately 90% IgG, IgA, and IgM and 10% albumin. Fractogel® TMAE, equilibrated in 25 mM sodium acetate-pH 6.0 and loaded with up to 225 mg of IgG/mL, could remove IgA and IgM, with over 94% IgG recovery with preserved sub-class distribution in the flow-through. Sequential Eshmuno®-P anti-A and anti-B columns efficiently removed isoagglutinins. The C18 packing, used at up to 17 mL of S/D-IgG solution per mL, removed TnBP and Triton X-100 to less than 1 and 2 ppm, respectively. The 20% purified IgG was devoid of activated factor XI and thrombin generation activity | ||
| 520 | |a DISCUSSION: This purification sequence yields a >99% pure, 20% (v/v) IgG product, depleted of IgA, isoagglutinins, and thrombogenic markers, and should be implementable on various IgG intermediates to help improve the supply of immunoglobulins | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Immunoglobulin A |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Immunoglobulin M |2 NLM | |
| 700 | 1 | |a Wu, Yu-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chen-Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Sharon S |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Cheum L |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Karen W |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Leo X |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Xisheng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Burnouf, Thierry |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Blood transfusion = Trasfusione del sangue |d 2007 |g 19(2021), 6 vom: 02. Nov., Seite 467-478 |w (DE-627)NLM181212099 |x 2385-2070 |7 nnns |
| 773 | 1 | 8 | |g volume:19 |g year:2021 |g number:6 |g day:02 |g month:11 |g pages:467-478 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.2450/2021.0159-21 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 19 |j 2021 |e 6 |b 02 |c 11 |h 467-478 | ||