Carpenter J.,University of Colorado at Boulder |
Cherney B.,Therapeutic Proteins |
Lubinecki A.,Pharmaceutical Development and Manufacturing science |
Ma S.,Genentech |
And 6 more authors.
Biologicals | Year: 2010
This meeting was successful in achieving its main goals: (1) summarize currently available information on the origin, detection, quantification and characterization of sub-visible particulates in protein products, available information on their clinical importance, and potential strategies for evaluating and mitigating risk to product quality, and (2) foster communication among academic, industry, and regulatory scientists to define the capabilities of current analytical methods, to promote the development of improved methods, and to stimulate investigations into the impact of large protein aggregates on immunogenicity. There was a general consensus that a considerable amount of interesting scientific information was presented and many stimulating conversations were begun. It is clear that this aspect of protein characterization is in its initial stages. As the development of these new methods progress, it is hoped that they will shed light on the role of protein particulates on product quality, safety, and efficacy. A topic which seemed appropriate for short term follow up was to hold further discussions concerning the development and preparation of one or more standard preparations of protein particulates. This would be generally useful to facilitate comparison of results among different studies, methods, and laboratories, and to foster further development of a common understanding among laboratories and health authorities which is essential to making further progress in this emerging field. © 2010.
Salas-Solano O.,Seattle Genetics |
Kennel B.,Bristol Myers Squibb |
Park S.S.,Amgen Inc. |
Roby K.,BioPharma Solutions |
And 13 more authors.
Journal of Separation Science | Year: 2012
An international team including 12 laboratories from 11 independent biopharmaceutical companies in the United States and Switzerland was formed to evaluate the precision and robustness of imaged capillary isoelectric focusing for the charge heterogeneity analysis of monoclonal antibodies. The different laboratories determined the apparent pI and the relative distribution of the charged isoforms for a representative monoclonal antibody sample using the same capillary isoelectric focusing assay. Statistical evaluation of the data was performed to determine within and between laboratory consistencies and outlying information. The apparent pI data generated for each charged variant peak showed very good precision between laboratories with RSD values of less than 0.8%. Similarly, the RSD for the therapeutic monoclonal antibody charged variants percent peak area values are less than 11% across different laboratories using different analyst, different lots of ampholytes and multiple instruments. These results validate the appropriate use of imaged capillary isoelectric focusing in the biopharmaceutical industry in support of process development and regulatory submissions of therapeutic antibodies. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Salas-Solano O.,Seattle Genetics |
Babu K.,Bristol Myers Squibb |
Park S.S.,Amgen Inc. |
Zhang X.,Amgen Inc. |
And 18 more authors.
Chromatographia | Year: 2011
Interlaboratory comparisons are essential to bringing emerging technologies into biopharmaceutical industry practice and regulatory acceptance. As a result, an international team including 12 laboratories from 10 independent biopharmaceutical companies in the United States and Switzerland was formed to evaluate the precision and robustness of capillary isoelectric focusing (CIEF) to assess the charge heterogeneity of monoclonal antibodies. The different laboratories determined the apparent pI and the relative distribution of the charge isoforms of a representative monoclonal antibody (rMAb) sample using the same CIEF method. Statistical evaluation of the data was performed to determine within and between-laboratory consistencies and outlying information. The apparent pI data generated for each charge variant peak showed very good precision between laboratories with percentage of RSD values of ≤0.5%. Similarly, the percentage of RSD for the rMAb charge variants percent peak area values are ≤4.4% across different laboratories with different analysts using different lots of ampholytes and multiple instruments. Taken together, these results validate the appropriate use of CIEF in the biopharmaceutical industry in support of regulatory submissions. © 2011 Springer-Verlag.
Teeters M.,Pharmaceutical Development and Manufacturing science |
Bezila D.,Pharmaceutical Development and Manufacturing science |
Benner T.,Pharmaceutical Development and Manufacturing science |
Alfonso P.,Pharmaceutical Development and Manufacturing science |
Alred P.,Pharmaceutical Development and Manufacturing science
Biotechnology and Bioengineering | Year: 2011
Many liquid formulations for monoclonal antibodies (MAbs) require the final ultrafiltration/diafiltration step to operate at high protein concentrations, often at or above 100g/L. When operating under these conditions, the excipient concentrations and pH of the final diafiltered retentate are frequently not equal to the corresponding excipient concentrations and pH of the diafiltration buffer. A model based on the Poisson-Boltzmann equation combined with volume exclusion was extended to predict both pH and excipient concentrations in the retentate for a given diafiltration buffer. This model was successfully applied to identify the diafiltration buffer composition required to achieve the desired pre-formulated bulk drug substance (retentate) conditions. Predictions were in good agreement with the experimental results, and reduced the number of experimental iterations needed to define the diafiltration buffer composition. Additionally, the predictive model was applied in a sensitivity analysis across ranges of protein charge, protein concentration, and diafiltration buffer pH and excipient concentration. This sensitivity analysis can facilitate the design of experiments for robustness testing, and allow for generalized predictions across classes of molecules such as MAbs. © 2011 Wiley Periodicals, Inc.