PMID- 28211938
OWN - NLM
STAT- MEDLINE
DCOM- 20170918
LR  - 20171106
IS  - 1522-2683 (Electronic)
IS  - 0173-0835 (Linking)
VI  - 38
IP  - 9-10
DP  - 2017 May
TI  - Establishment and validation of a microfluidic capillary gel electrophoresis 
      platform method for purity analysis of therapeutic monoclonal antibodies.
PG  - 1353-1365
LID - 10.1002/elps.201600519 [doi]
AB  - Capillary and microfluidic chip electrophoresis technologies are heavily utilized 
      for development, characterization, release, and stability testing of 
      biopharmaceuticals. Within the biopharmaceutical industry, CE-SDS and M-CGE are 
      commonly used for purity determination by separation and quantitation of 
      size-based variants. M-CGE is used primarily as an R&D tool for product and 
      process development, while cGMP release and stability testing applications are 
      commonly reserved for CE-SDS. This paper describes the establishment of an M-CGE 
      platform method to be used for R&D and cGMP applications, including release and 
      stability testing, for monoclonal antibodies. The M-CGE platform method enables 
      testing for product development support and cGMP release and stability using the 
      same method, and utilization of one CE technology for the entire lifecycle of a 
      biopharmaceutical product. Critical method parameters were identified, and the 
      analytical design space of those critical parameters was defined using design of 
      experiments (DOE) studies. Once defined through DOE studies, the method design 
      space was validated according to ICH Q2 (R1) guidelines. Additional molecules of 
      the same validated class were verified for use in the method by experimental 
      confirmation of accuracy, specificity, and stability indicating capabilities. The 
      platform method model facilitates rapid utilization of the method in development 
      and GMP testing environments, and eliminates the need for individual validations 
      for assets of the same class entering early stage development.
CI  - (c) 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Smith, Michael T
AU  - Smith MT
AD  - Biopharmaceutical Analytical Sciences, GlaxoSmithKline LLC, King of Prussia, PA, 
      USA.
FAU - Zhang, Shu
AU  - Zhang S
AD  - Statistical Sciences, GlaxoSmithKline LLC, King of Prussia, PA, USA.
FAU - Adams, Troy
AU  - Adams T
AD  - Biopharmaceutical Analytical Sciences, GlaxoSmithKline LLC, King of Prussia, PA, 
      USA.
FAU - DiPaolo, Byron
AU  - DiPaolo B
AD  - Biopharmaceutical Analytical Sciences, GlaxoSmithKline LLC, King of Prussia, PA, 
      USA.
FAU - Dally, Jennifer
AU  - Dally J
AD  - Biopharmaceutical Analytical Sciences, GlaxoSmithKline LLC, King of Prussia, PA, 
      USA.
LA  - eng
PT  - Journal Article
DEP - 20170406
PL  - Germany
TA  - Electrophoresis
JT  - Electrophoresis
JID - 8204476
RN  - 0 (Antibodies, Monoclonal)
SB  - IM
MH  - Antibodies, Monoclonal/*analysis/*chemistry
MH  - Drug Contamination
MH  - Electrophoresis, Capillary/*methods
MH  - Limit of Detection
MH  - Linear Models
MH  - Microfluidic Analytical Techniques/*methods
MH  - Protein Stability
MH  - Reproducibility of Results
OTO - NOTNLM
OT  - CGE
OT  - Microfluidic
OT  - Monoclonal antibody
OT  - Platform method
OT  - Validation
EDAT- 2017/02/18 06:00
MHDA- 2017/09/19 06:00
CRDT- 2017/02/18 06:00
PHST- 2016/11/22 00:00 [received]
PHST- 2017/02/10 00:00 [revised]
PHST- 2017/02/13 00:00 [accepted]
PHST- 2017/02/18 06:00 [pubmed]
PHST- 2017/09/19 06:00 [medline]
PHST- 2017/02/18 06:00 [entrez]
AID - 10.1002/elps.201600519 [doi]
PST - ppublish
SO  - Electrophoresis. 2017 May;38(9-10):1353-1365. doi: 10.1002/elps.201600519. Epub 
      2017 Apr 6.