J&J’s recent recall of Motrin and other pharmaceutical products is more than a cautionary tale in crisis management. It raises a very important question: Why do companies hesitate to address known risks (in this case the QC problems at a specific manufacturing facility)? As Douglas McIntyre, editor of 24/7 Wall Street, stated in a recent posting, “Acting early would probably be harmless at worst and might be critical to success.” However, he admits that few companies have gotten the message. But why?…
BioProcessing Journal Posts
Process optimization is a key development step that precedes scale-up and tech-transfer in a manufacturing environment. New England Biolabs (NEB) and GE Healthcare (GEHC) set the objective of improving filtration clarification and concentration process steps with the target of improving overall efficiency, and reducing the labor time and expense associated with these unit operations…
This investigation into the light isomerization of tropolone was initiated after a method for determining residual tropolone in the bulk drug substance (BDS) of a therapeutic monoclonal antibody was developed and validated at our laboratory. This method, developed at a client’s request, required a detection limit of 50 parts per billion (ppb) in the BDS to meet their regulatory requirements. The method was developed using liquid chromatography and tandem mass spectrometry (LC/MS/MS) because of the selectivity and sensitivity of the technique when using selective reaction monitoring (SRM). During development, however, it was discovered that only after creating a photoisomer of tropolone could successful separation, detection, and quantitation of tropolone be achieved. During validation, the method showed good performance…
Classical filtration fouling models do not accurately predict fouling behaviors for sterilizing filtration applied to some bioprocess fluids, particularly when filters are operated in series. To overcome the limitations of these models, we extended a previously developed single-stage fouling model that combined blocking and adsorption mechanisms to dual filters operated in series. Our model demonstrates improvements in predicting bioprocess fluid filtration performance accuracy when applied to microfiltration membranes operated in series, from measured performance of each membrane filter operated individually. In addition, the model and developed method allows for rapid and efficient optimization of prefiltration to final filter area ratios. In redundant sterile filtration, two filters with the same pore size rating are operated in series to protect against an integrity failure of the primary sterilizing filter. Prefilters can also be used to protect final sterilizing-grade membrane filters from excessive fouling which in turn offer the benefits of reduced costs and filtration time…
The impact of individual and interactive behaviors of various fermentation process parameters on laccase and peroxidase-free tyrosinase production were investigated by isolated Streptomyces antibioticus RSP-T1. Six key bioprocess factors (medium pH, rpm, incubation time, sodium chloride concentration, complex nitrogen [yeast extract + peptone], and carbon source [maltose]) were selected based on using a one variable at a time methodology. All selected parameters had an impact at individual and interactive levels on tyrosinase production. Only 25% of the improved tyrosinase production was attributed to the optimized fermentation parameters selected. Regarding the nutritional parameters, the complex nitrogen/carbon source concentration (maltose and yeast extract + peptone) was found to have the most significance impact on overall tyrosinase enzyme production. Physiological growth factors (pH, rpm, and incubation time) played key roles at an interactive level. A maximum yield of 12.60 IU/mL tyrosinase production was achieved with optimized medium, adjusted to 7.5 pH, consisting of 0.75% maltose (w/v), 0.2% yeast extract (w/v), 0.2% peptone (w/v), and 1.25% sodium chloride (w/v) at 160 rpm in 24 hours. This study identified the optimum medium component concentrations for improved tyrosinase production by S. antibioticus RSP-T1. This strain requires complex nitrogen sources (yeast extract and peptone) for increased product yield. Overall, a greater than 250% increase in tyrosinase production was achieved using this optimization approach, as compared to conventional methods…
Viral clearance studies are required for pharmaceuticals derived from human and/or animal sources such as recombinant proteins produced in eukaryotic cell lines, human blood products and vaccines, and even for some critical class III medical devices. It is mandatory to demonstrate that steps in the manufacturing process are capable of inactivating or removing potential viral contaminants. For this, a laboratory-scale (downscale) of the process step is developed and challenged with different model virus solutions. The viral concentrations are quantitatively determined in the feed material and the relevant product fraction. The ratio of both defines the reduction in virus and specifies the viral inactivation or viral removal capacity of the investigated process step…
Biosimilars, and related biopharmaceutical biobetters and biogenerics, are still relatively new, but are already starting to impact worldwide biopharmaceutical markets. Most discussions of biosimilars center on developed regions where markets are mature and manufacturing capabilities allow for the cost-efficient manufacture of these complex molecules. This article covers the development of these products outside the United States (US), European Union (EU), and other developed, generally rather affluent and high-technology economy-based countries. To start, we first offer some definitions…