PMID- 27522919
OWN - NLM
STAT- MEDLINE
DCOM- 20171031
LR  - 20171127
IS  - 1520-6017 (Electronic)
IS  - 0022-3549 (Linking)
VI  - 105
IP  - 10
DP  - 2016 Oct
TI  - Accelerating Vaccine Formulation Development Using Design of Experiment Stability 
      Studies.
PG  - 3046-3056
LID - S0022-3549(16)41512-1 [pii]
LID - 10.1016/j.xphs.2016.06.014 [doi]
AB  - Vaccine drug product thermal stability often depends on formulation input factors 
      and how they interact. Scientific understanding and professional experience 
      typically allows vaccine formulators to accurately predict the thermal stability 
      output based on formulation input factors such as pH, ionic strength, and 
      excipients. Thermal stability predictions, however, are not enough for 
      regulators. Stability claims must be supported by experimental data. The Quality 
      by Design approach of Design of Experiment (DoE) is well suited to describe 
      formulation outputs such as thermal stability in terms of formulation input 
      factors. A DoE approach particularly at elevated temperatures that induce 
      accelerated degradation can provide empirical understanding of how vaccine 
      formulation input factors and interactions affect vaccine stability output 
      performance. This is possible even when clear scientific understanding of 
      particular formulation stability mechanisms are lacking. A DoE approach was used 
      in an accelerated 37( degrees )C stability study of an aluminum adjuvant Neisseria 
      meningitidis serogroup B vaccine. Formulation stability differences were 
      identified after only 15 days into the study. We believe this study demonstrates 
      the power of combining DoE methodology with accelerated stress stability studies 
      to accelerate and improve vaccine formulation development programs particularly 
      during the preformulation stage.
CI  - Copyright (c) 2016 American Pharmacists Association(R). Published by Elsevier Inc. 
      All rights reserved.
FAU - Ahl, Patrick L
AU  - Ahl PL
AD  - Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & 
      Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & 
      Co., Inc., Kenilworth, New Jersey 07033. Electronic address: 
      patrick_ahl@merck.com.
FAU - Mensch, Christopher
AU  - Mensch C
AD  - Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & 
      Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & 
      Co., Inc., Kenilworth, New Jersey 07033.
FAU - Hu, Binghua
AU  - Hu B
AD  - Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & 
      Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & 
      Co., Inc., Kenilworth, New Jersey 07033.
FAU - Pixley, Heidi
AU  - Pixley H
AD  - Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & 
      Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & 
      Co., Inc., Kenilworth, New Jersey 07033.
FAU - Zhang, Lan
AU  - Zhang L
AD  - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033; 
      Infectious Diseases and Vaccines Discovery, Merck Research Laboratories, Merck & 
      Co., Inc., West Point, Pennsylvania 19486.
FAU - Dieter, Lance
AU  - Dieter L
AD  - Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & 
      Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & 
      Co., Inc., Kenilworth, New Jersey 07033.
FAU - Russell, Ryann
AU  - Russell R
AD  - Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & 
      Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & 
      Co., Inc., Kenilworth, New Jersey 07033.
FAU - Smith, William J
AU  - Smith WJ
AD  - Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & 
      Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & 
      Co., Inc., Kenilworth, New Jersey 07033.
FAU - Przysiecki, Craig
AU  - Przysiecki C
AD  - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033; 
      Infectious Diseases and Vaccines Discovery, Merck Research Laboratories, Merck & 
      Co., Inc., West Point, Pennsylvania 19486.
FAU - Kosinski, Mike
AU  - Kosinski M
AD  - Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & 
      Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & 
      Co., Inc., Kenilworth, New Jersey 07033.
FAU - Blue, Jeffrey T
AU  - Blue JT
AD  - Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & 
      Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & 
      Co., Inc., Kenilworth, New Jersey 07033.
LA  - eng
PT  - Journal Article
DEP - 20160811
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Vaccines)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage/*chemistry
MH  - Animals
MH  - Chemistry, Pharmaceutical
MH  - Drug Compounding/*methods/trends
MH  - *Drug Design
MH  - Drug Stability
MH  - Female
MH  - Meningitis, Meningococcal/immunology/prevention & control
MH  - Mice
MH  - Neisseria meningitidis/drug effects/immunology
MH  - Vaccines/administration & dosage/*chemistry/immunology
OTO - NOTNLM
OT  - analytical biochemistry
OT  - biotechnology
OT  - excipients
OT  - stability
OT  - vaccine adjuvants
OT  - vaccines
EDAT- 2016/08/16 06:00
MHDA- 2017/11/01 06:00
CRDT- 2016/08/16 06:00
PHST- 2016/04/12 00:00 [received]
PHST- 2016/05/20 00:00 [revised]
PHST- 2016/06/09 00:00 [accepted]
PHST- 2016/08/16 06:00 [entrez]
PHST- 2016/08/16 06:00 [pubmed]
PHST- 2017/11/01 06:00 [medline]
AID - S0022-3549(16)41512-1 [pii]
AID - 10.1016/j.xphs.2016.06.014 [doi]
PST - ppublish
SO  - J Pharm Sci. 2016 Oct;105(10):3046-3056. doi: 10.1016/j.xphs.2016.06.014. Epub 
      2016 Aug 11.