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An Approach to Mitigate Particle Formation on the Dilution of a Monoclonal Antibody Drug Product in an IV Administration Fluid.

Abstract To support dose reduction, low dose of a monoclonal antibody (mAb) was required to be administered via IV infusion at a concentration of 0.1 mg/mL. To achieve the target protein concentration, the infusion solution was prepared by diluting the drug product containing 10-mg/mL mAb with normal saline, a 0.9% sodium chloride injection solution. However, particles were observed in the diluted solution. Particle formation must be avoided to administer the low dose using the existing drug product. To mitigate the particle formation, an unconventional compounding approach was used. With this approach, a stabilizing vehicle containing polysorbate-80 was added to saline before drug-product dilution to maintain suitable surfactant level to prevent precipitation of the mAb. In this way, use of the stabilizing vehicle to support low doses ensured suitable quality across a wider range of mAb concentrations, thereby allowing additional flexibility to the clinical trial. Such an approach may be useful for broader application in early-stage clinical trials where there is an uncertainty regarding doses or the need to revise to lower doses based on clinical observations or other drivers.
PMID
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Authors

Mayor MeshTerms
Keywords

precipitation

preformulation

protein aggregation

protein formulation

protein structure

Journal Title journal of pharmaceutical sciences
Publication Year Start
%A Zheng, Songyan; Adams, Monica; Mantri, Rao V.
%T An Approach to Mitigate Particle Formation on the Dilution of a Monoclonal Antibody Drug Product in an IV Administration Fluid.
%J Journal of pharmaceutical sciences, vol. 105, no. 3, pp. 1349-1350
%D 03/2016
%V 105
%N 3
%M eng
%B To support dose reduction, low dose of a monoclonal antibody (mAb) was required to be administered via IV infusion at a concentration of 0.1 mg/mL. To achieve the target protein concentration, the infusion solution was prepared by diluting the drug product containing 10-mg/mL mAb with normal saline, a 0.9% sodium chloride injection solution. However, particles were observed in the diluted solution. Particle formation must be avoided to administer the low dose using the existing drug product. To mitigate the particle formation, an unconventional compounding approach was used. With this approach, a stabilizing vehicle containing polysorbate-80 was added to saline before drug-product dilution to maintain suitable surfactant level to prevent precipitation of the mAb. In this way, use of the stabilizing vehicle to support low doses ensured suitable quality across a wider range of mAb concentrations, thereby allowing additional flexibility to the clinical trial. Such an approach may be useful for broader application in early-stage clinical trials where there is an uncertainty regarding doses or the need to revise to lower doses based on clinical observations or other drivers.
%P 1349
%L 1350
%Y 10.1016/j.xphs.2015.12.013
%W PHY
%G AUTHOR
%R 2016......105.1349Z

@Article{Zheng2016,
author="Zheng, Songyan
and Adams, Monica
and Mantri, Rao V.",
title="An Approach to Mitigate Particle Formation on the Dilution of a Monoclonal Antibody Drug Product in an IV Administration Fluid.",
journal="Journal of pharmaceutical sciences",
year="2016",
month="Mar",
day="30",
volume="105",
number="3",
pages="1349--1350",
abstract="To support dose reduction, low dose of a monoclonal antibody (mAb) was required to be administered via IV infusion at a concentration of 0.1 mg/mL. To achieve the target protein concentration, the infusion solution was prepared by diluting the drug product containing 10-mg/mL mAb with normal saline, a 0.9\% sodium chloride injection solution. However, particles were observed in the diluted solution. Particle formation must be avoided to administer the low dose using the existing drug product. To mitigate the particle formation, an unconventional compounding approach was used. With this approach, a stabilizing vehicle containing polysorbate-80 was added to saline before drug-product dilution to maintain suitable surfactant level to prevent precipitation of the mAb. In this way, use of the stabilizing vehicle to support low doses ensured suitable quality across a wider range of mAb concentrations, thereby allowing additional flexibility to the clinical trial. Such an approach may be useful for broader application in early-stage clinical trials where there is an uncertainty regarding doses or the need to revise to lower doses based on clinical observations or other drivers.",
issn="1520-6017",
doi="10.1016/j.xphs.2015.12.013",
url="http://www.ncbi.nlm.nih.gov/pubmed/26886343",
language="eng"
}

%0 Journal Article
%T An Approach to Mitigate Particle Formation on the Dilution of a Monoclonal Antibody Drug Product in an IV Administration Fluid.
%A Zheng, Songyan
%A Adams, Monica
%A Mantri, Rao V.
%J Journal of pharmaceutical sciences
%D 2016
%8 Mar 30
%V 105
%N 3
%@ 1520-6017
%G eng
%F Zheng2016
%X To support dose reduction, low dose of a monoclonal antibody (mAb) was required to be administered via IV infusion at a concentration of 0.1 mg/mL. To achieve the target protein concentration, the infusion solution was prepared by diluting the drug product containing 10-mg/mL mAb with normal saline, a 0.9% sodium chloride injection solution. However, particles were observed in the diluted solution. Particle formation must be avoided to administer the low dose using the existing drug product. To mitigate the particle formation, an unconventional compounding approach was used. With this approach, a stabilizing vehicle containing polysorbate-80 was added to saline before drug-product dilution to maintain suitable surfactant level to prevent precipitation of the mAb. In this way, use of the stabilizing vehicle to support low doses ensured suitable quality across a wider range of mAb concentrations, thereby allowing additional flexibility to the clinical trial. Such an approach may be useful for broader application in early-stage clinical trials where there is an uncertainty regarding doses or the need to revise to lower doses based on clinical observations or other drivers.
%U http://dx.doi.org/10.1016/j.xphs.2015.12.013
%U http://www.ncbi.nlm.nih.gov/pubmed/26886343
%P 1349-1350

PT Journal
AU Zheng, S
   Adams, M
   Mantri, RV
TI An Approach to Mitigate Particle Formation on the Dilution of a Monoclonal Antibody Drug Product in an IV Administration Fluid.
SO Journal of pharmaceutical sciences
JI J Pharm Sci
PD Mar
PY 2016
BP 1349
EP 1350
VL 105
IS 3
DI 10.1016/j.xphs.2015.12.013
LA eng
AB To support dose reduction, low dose of a monoclonal antibody (mAb) was required to be administered via IV infusion at a concentration of 0.1 mg/mL. To achieve the target protein concentration, the infusion solution was prepared by diluting the drug product containing 10-mg/mL mAb with normal saline, a 0.9% sodium chloride injection solution. However, particles were observed in the diluted solution. Particle formation must be avoided to administer the low dose using the existing drug product. To mitigate the particle formation, an unconventional compounding approach was used. With this approach, a stabilizing vehicle containing polysorbate-80 was added to saline before drug-product dilution to maintain suitable surfactant level to prevent precipitation of the mAb. In this way, use of the stabilizing vehicle to support low doses ensured suitable quality across a wider range of mAb concentrations, thereby allowing additional flexibility to the clinical trial. Such an approach may be useful for broader application in early-stage clinical trials where there is an uncertainty regarding doses or the need to revise to lower doses based on clinical observations or other drivers.
ER

PMID- 26886343
OWN - NLM
STAT- In-Process
DA  - 20160301
IS  - 1520-6017 (Electronic)
IS  - 0022-3549 (Linking)
VI  - 105
IP  - 3
DP  - 2016 Mar
TI  - An Approach to Mitigate Particle Formation on the Dilution of a Monoclonal
      Antibody Drug Product in an IV Administration Fluid.
PG  - 1349-50
LID - 10.1016/j.xphs.2015.12.013 [doi]
LID - S0022-3549(15)00238-5 [pii]
AB  - To support dose reduction, low dose of a monoclonal antibody (mAb) was required
      to be administered via IV infusion at a concentration of 0.1 mg/mL. To achieve
      the target protein concentration, the infusion solution was prepared by diluting 
      the drug product containing 10-mg/mL mAb with normal saline, a 0.9% sodium
      chloride injection solution. However, particles were observed in the diluted
      solution. Particle formation must be avoided to administer the low dose using the
      existing drug product. To mitigate the particle formation, an unconventional
      compounding approach was used. With this approach, a stabilizing vehicle
      containing polysorbate-80 was added to saline before drug-product dilution to
      maintain suitable surfactant level to prevent precipitation of the mAb. In this
      way, use of the stabilizing vehicle to support low doses ensured suitable quality
      across a wider range of mAb concentrations, thereby allowing additional
      flexibility to the clinical trial. Such an approach may be useful for broader
      application in early-stage clinical trials where there is an uncertainty
      regarding doses or the need to revise to lower doses based on clinical
      observations or other drivers.
CI  - Copyright (c) 2016. Published by Elsevier Inc.
FAU - Zheng, Songyan
AU  - Zheng S
AD  - Drug Product Science and Technology, Pharmaceutical Development, Research and
      Development, Bristol-Myers Squibb, New Brunswick, New Jersey 08903. Electronic
      address: [email protected]
FAU - Adams, Monica
AU  - Adams M
AD  - Drug Product Science and Technology, Pharmaceutical Development, Research and
      Development, Bristol-Myers Squibb, New Brunswick, New Jersey 08903.
FAU - Mantri, Rao V
AU  - Mantri RV
AD  - Drug Product Science and Technology, Pharmaceutical Development, Research and
      Development, Bristol-Myers Squibb, New Brunswick, New Jersey 08903.
LA  - eng
PT  - Journal Article
DEP - 20160130
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
SB  - IM
OTO - NOTNLM
OT  - precipitation
OT  - preformulation
OT  - protein aggregation
OT  - protein formulation
OT  - protein structure
EDAT- 2016/02/18 06:00
MHDA- 2016/02/18 06:00
CRDT- 2016/02/18 06:00
PHST- 2015/09/18 [received]
PHST- 2015/12/04 [revised]
PHST- 2015/12/15 [accepted]
PHST- 2016/01/30 [aheadofprint]
AID - S0022-3549(15)00238-5 [pii]
AID - 10.1016/j.xphs.2015.12.013 [doi]
PST - ppublish
SO  - J Pharm Sci. 2016 Mar;105(3):1349-50. doi: 10.1016/j.xphs.2015.12.013. Epub 2016 
      Jan 30.
TY  - JOUR
AU  - Zheng, Songyan
AU  - Adams, Monica
AU  - Mantri, Rao V.
PY  - 2016/Mar/30
TI  - An Approach to Mitigate Particle Formation on the Dilution of a Monoclonal Antibody Drug Product in an IV Administration Fluid.
T2  - J Pharm Sci
JO  - Journal of pharmaceutical sciences
SP  - 1349
EP  - 1350
VL  - 105
IS  - 3
N2  - To support dose reduction, low dose of a monoclonal antibody (mAb) was required to be administered via IV infusion at a concentration of 0.1 mg/mL. To achieve the target protein concentration, the infusion solution was prepared by diluting the drug product containing 10-mg/mL mAb with normal saline, a 0.9% sodium chloride injection solution. However, particles were observed in the diluted solution. Particle formation must be avoided to administer the low dose using the existing drug product. To mitigate the particle formation, an unconventional compounding approach was used. With this approach, a stabilizing vehicle containing polysorbate-80 was added to saline before drug-product dilution to maintain suitable surfactant level to prevent precipitation of the mAb. In this way, use of the stabilizing vehicle to support low doses ensured suitable quality across a wider range of mAb concentrations, thereby allowing additional flexibility to the clinical trial. Such an approach may be useful for broader application in early-stage clinical trials where there is an uncertainty regarding doses or the need to revise to lower doses based on clinical observations or other drivers.
SN  - 1520-6017
UR  - http://dx.doi.org/10.1016/j.xphs.2015.12.013
UR  - http://www.ncbi.nlm.nih.gov/pubmed/26886343
ID  - Zheng2016
ER  - 
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