PMID- 21920692
OWN - NLM
STAT- MEDLINE
DCOM- 20120130
LR  - 20111011
IS  - 1873-264X (Electronic)
IS  - 0731-7085 (Linking)
VI  - 57
DP  - 2012 Jan 5
TI  - Aggregation factor analysis for protein formulation by a systematic approach 
      using FTIR, SEC and design of experiments techniques.
PG  - 143-52
LID - 10.1016/j.jpba.2011.08.035 [doi]
AB  - A simple systematic approach using Fourier transform infrared (FTIR) 
      spectroscopy, size exclusion chromatography (SEC) and design of experiments (DOE) 
      techniques was applied to the analysis of aggregation factors for protein 
      formulations in stress and accelerated testings. FTIR and SEC were used to 
      evaluate protein conformational and storage stabilities, respectively. DOE was 
      used to determine the suitable formulation and to analyze both the main effect of 
      single factors and the interaction effect of combined factors on aggregation. Our 
      results indicated that (i) analysis at a low protein concentration is not always 
      applicable to high concentration formulations; (ii) an investigation of 
      interaction effects of combined factors as well as main effects of single factors 
      is effective for improving conformational stability of proteins; (iii) with the 
      exception of pH, the results of stress testing with regard to aggregation factors 
      would be available for suitable formulation instead of performing time-consuming 
      accelerated testing; (iv) a suitable pH condition should not be determined in 
      stress testing but in accelerated testing, because of inconsistent effects of pH 
      on conformational and storage stabilities. In summary, we propose a three-step 
      strategy, using FTIR, SEC and DOE techniques, to effectively analyze the 
      aggregation factors and perform a rapid screening for suitable conditions of 
      protein formulation.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Feng, Yan Wen
AU  - Feng YW
AD  - National Institute of Advanced Industrial Science and Technology, Central 6, 
      1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
FAU - Ooishi, Ayako
AU  - Ooishi A
FAU - Honda, Shinya
AU  - Honda S
LA  - eng
PT  - Journal Article
DEP - 20110831
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 0 (Proteins)
SB  - IM
MH  - Chromatography, Gel/*methods
MH  - Factor Analysis, Statistical
MH  - Hydrogen-Ion Concentration
MH  - Protein Conformation
MH  - Proteins/*chemistry
MH  - Spectroscopy, Fourier Transform Infrared/*methods
MH  - Temperature
EDAT- 2011/09/17 06:00
MHDA- 2012/01/31 06:00
CRDT- 2011/09/17 06:00
PHST- 2011/05/28 00:00 [received]
PHST- 2011/08/24 00:00 [revised]
PHST- 2011/08/25 00:00 [accepted]
PHST- 2011/09/17 06:00 [entrez]
PHST- 2011/09/17 06:00 [pubmed]
PHST- 2012/01/31 06:00 [medline]
AID - S0731-7085(11)00491-2 [pii]
AID - 10.1016/j.jpba.2011.08.035 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2012 Jan 5;57:143-52. doi: 10.1016/j.jpba.2011.08.035. Epub 
      2011 Aug 31.