Sustainable reduction of bioreactor contamination in an industrial fermentation pilot plant.
Facility experience primarily in drug-oriented fermentation equipment (producing small molecules such as secondary metabolites, bioconversions, and enzymes) and, to a lesser extent, in biologics-oriented fermentation equipment (producing large molecules such as recombinant proteins and microbial vaccines) in an industrial fermentation pilot plant over the past 15 years is described. Potential approaches for equipment design and maintenance, operational procedures, validation/verification testing, medium selection, culture purity/sterility analysis, and contamination investigation are presented, and those approaches implemented are identified. Failure data collected for pilot plant operation for nearly 15 years are presented and best practices for documentation and tracking are outlined. This analysis does not exhaustively discuss available design, operational and procedural options; rather it selectively presents what has been determined to be beneficial in an industrial pilot plant setting. Literature references have been incorporated to provide background and context where appropriate.
Junker
Beth
B
RY810-127, Merck Research Laboratories, Fermentation Development and Operations, Rahway, NJ 07065, USA. beth_junker@merck.com
Lester
Michael
M
Leporati
James
J
Schmitt
John
J
Kovatch
Michael
M
Borysewicz
Stan
S
Maciejak
Waldemar
W
Seeley
Anna
A
Hesse
Michelle
M
Connors
Neal
N
Brix
Thomas
T
Creveling
Eric
E
Salmon
Peter
P
D019149:Bioreactors / Q000382:microbiology*; D003666:Decontamination / Q000295:instrumentation / Q000379:methods*; D004866:Equipment Contamination / Q000517:prevention & control*; D019544:Equipment Failure Analysis / Q000295:instrumentation / Q000379:methods*; D005285:Fermentation; D007218:Industrial Microbiology / Q000295:instrumentation* / Q000379:methods; D008283:Maintenance / Q000379:methods*; D010865:Pilot Projects