Genetic Engineering & Biotechnology News

SEP15 2017

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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24 | SEPTEMBER 15, 2017 | | Genetic Engineering & Biotechnology News Michael F. Drenski Static light scattering is widely used to mea- sure the molar masses of molecules, particles, and their aggregates under various solution conditions and compositions. A light scatter- ing–based instrument from Fluence Analytics can run 16 independent light-scattering ex- periments simultaneously under varying stressor conditions. With this instrument, an aggregation rate generator called Argen (Figure 1), each sample can be independently stressed by any combination of thermal con- dition (between 18–100 °C) and stirring con- dition (between 0 and 2,000 rpm). The light-scattering signature is con- tinuously monitored throughout the ex- periment, providing a direct indication of a stress-induced change to the sample. These stresses and resulting effects on the samples' formulation stability can be directly moni- tored and quantified with the Argen system to reveal any change in both absolute mo- lecular weight and normalized molecular weight throughout aggregation or degrada- tion processes. While this note exemplifies the use of Argen to characterize monoclonal antibod- ies (mAbs), the the monitoring and analysis methods described herein are easily translat- able to nearly all soluble synthetic and natu- ral products. These methods can be used to generate Arrhenius representations of aggre- gation rate, facilitating direct and vivid com- parisons of stability for samples subjected to different stressors, such as formulation con- dition (pH and ionic strength) and composi- tion (excipient and surfactant content). The Arrhenius plot also yields activation energy over one or more thermal regimes. Methodology In this study, a monoclonal antibody was monitored in a set of 16 independent temperatures to determine the aggrega- tion rate (AR) behavior. To eliminate as many variables as possible, the sample was prepared in a single buffer formulation at a fixed concentration of 1 mg/mL. The tem- perature, however, was isothermally varied from 50-80 °C to test the molecule for ther- mal stability and determine the AR value at each isothermal condition. Figure 2 shows the time-dependent trend of normalized molecular weight (MW norm ) for the sample across a temperature spec- trum of 50–80 °C. The MW norm is calculated by dividing the raw light-scattering data by the initial molecular weight value (MW 0 ). As illustrated, the sample held at 80 °C aggre- gated to 10× its initial mass within 45 sec- onds, whereas the sample held at 50 °C did not show any significant aggregation after 14 hours of continuous monitoring. It is important to note that without the use of the simultaneous multiple sample light scattering (SMSLS) technique provided by Argen, each of these measurements would have to be carried out sequentially, equat- ing to nearly four days of continuous sample monitoring. Additionally, since all Argen data is collected continuously and in paral- lel, there is no discontinuity or loss of sig- nal resolution due to serial measurements or moving optical components. The measurements obtained with Argen support clear and concise interpretations of how any sample's aggregation behavior evolves over time. It is also clear that aggre- gation occurs over a wide range of tempera- tures, and hence there is no specific "aggre- gation temperature." Interpretation and Analysis The increase in light scattering from the initial MW 0 value is a direct representation of the sample's aggregation profile. Selection of the linear regime allows the user to eas- ily determine the linear aggregation rate of Using a Novel Methodology to Generate Aggregation Rates Determining Stability of mAb Formulations Bioprocessing Tutorial Figure 2: Temperature- dependent aggregation profiles. Figure 3: Arrhenius plot for experiments at 50–80 °C. Figure 1. Argen instrument. Insights Bioprocessing Lonza says its Pharma & Biotech segment is expand- ing in parenteral dosage form development with an additional build-out of its Drug Product Services (DPS). Company officials note that the investment will en- large both capability and capacity of DPS at the Stücki Science Park in Basel, Switzerland, including new capa- bilities for drug product process development. DPS began it lab business last November initially fo- cusing on formulation development and drug product analytical development. The facility was recently granted a GMP license after a successful audit by Swissmedic al- lowing QC release and stability testing of drug products. "This significant expansion represents an impor- tant milestone in Lonza's evolution to become a fully integrated drug development partner. With the recent acquisition of Capsule, combined with DPS's excel- lence in parenterals, we offer a wide range of services to meet our customers' drug product needs," said Marc Funk, COO of Lonza's Pharma & Biotech segment. "Our expansion in Basel also signals Lonza's strong commit- ment to the local community." According to Funk, DPS' approach to drug product development anticipates and prevents problems early and helps ensure the product is optimal for manu- facture, supply chain, and patient use. A complete portfolio of services for parenteral dosage forms is available, including products for injection and infusion for intravenous, subcutaneous, and intraocular routes of administration. These offerings also include specialized services, including particulate identification, characterization and quantification, excipient and surfactant charac- terization, extractable and leachables assessment, and container closure integrity testing. "The expansion of drug product services reflects the value that Lonza brings to our pharma and biotech customers through exceptional experience, a strong scientific track record and state-of-the-art instrumen- tal infrastructure which enables them to accelerate and de-risk Drug Product development and com- mercialization," said Prof Dr. Hanns-Christian Mahler, Lonza's head of drug product services. n Lonza Expands its Capabilities in Drug Product Services

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