Based on QbD principles, prior knowledge of the critical quality attributes and its potential impact on the safety and efficacy are strongly desired for mAb-based product development. Backbone and methyl group based 2D NMR fingerprinting provides for a robust technology to monitor HOS changes at an amino acid level during various stages of product development. Multiple attributes of mAbs can be monitored using a single NMR spectra acquired under non-denaturing solution conditions. In addition to the stress-induced impact on the global HOS, localized HOS changes spanning few residues that may be involved in functionally relevant protein-protein interactions can be monitored using NMR. A case study on the applications of NMR as a heightened characterization tool for bridging structure-function will be discussed.

Authors: Monica Sadek, Benjamin Moore, Zhiqi Hao, Chris Yu, Chengfeng Ren, Frank Macchi, Yan Chen, Milady Ninonuevo

Multi-Attribute Method (MAM) is a peptide–mapping based method that provides targeted monitoring of product quality attributes and non-targeted new peak detection. MAM has been implemented in the pharmaceutical industry for process development and is advancing into the Quality Control (QC) environment in alignment with Quality-by-Design principles. This talk describes the qualification of MAM as a potential platform method for QC at Genentech.

Cell line and cell culture development require a great deal of data to make good decisions.  Manual analytical workflows are resource intensive and inefficient, our approach at Biogen is to provide lab and data workflows that are highly automated.  Here we will discuss two cases where automated analytical approaches support Protein and Gene Therapy modalities.

Data Science is now an inescapable buzzword in biotech, but what does it mean in the biotherapeutic development context, and how can its tools be adopted productively? This talk will describe the foundations of a robust data science platform applied to early stage development, how it can be integrated across functional units, and its potential benefits to developmental and operational efficiency.

The complexity of our assays are constantly evolving. As a result, our sample throughput has increased and scientific workflows have become more dynamic, requiring a sophisticated sample processing paradigm. The need to scale, rapidly facilitate our experiments and intuitively curate the required hardware components in this tech-driven environment is incontrovertible. Providing essential infrastructure to fuel these advances can be challenging, but an innovative/progressive approach has been identified.Three functional advances aim to manage the evolution of drug discovery in our organization: in-house advanced robotics programming, part design/architecturing and the liquid-handling robot of the future. Our patent-pending TipSort technology has exploited mathematical optimization for robot/process efficiency, 3D printing in the lab has dispersed a variety of containers/adapters, serving the automation, and the Vantage robot has expanded our technological capabilities.

Biotherapeutics are heterogeneous in nature and may contain numerous variants with differences in size, charge, hydrophobicity, etc., which may impact clinical efficacy, immunogenicity, and safety. Characterization of biotherapeutic variants is necessary to build structure-function correlation and establish a proper control strategy. Isolation and enrichment of variants by conventional chromatographic peak fractionation is labor-intensive and time-consuming. The instability of fractions during isolation and subsequent characterization may also be a concern. Hence, it is desirable to characterize biotherapeutics in an online and real-time manner and 2D-LC may be a viable tool for this purpose. In this presentation, a few case studies will be discussed including charge and size variant characterization of a monoclonal antibody (mAb) and aggregate characterization of combination products.

Statistical comparison of quality attributes is important in many areas of pharmaceutical development, e.g. comparability, scale down model qualification, method transfer etc. Besides of well known equivalence test and similar Bayesian comparisons, new approaches will be presented, viewing the problem from a different, but basic angle: are minimum and maximum of both groups comparable? What about the results between minimum and maximum?

QbD quality study and determination of CQAs of biosimilar mAbs were performed following a developed platform at Henlius, which was applied in analytical similarity and process comparability studies of biosimilar mAbs. The major results of analytical similarity and process comparability on the 1st China biosimilar mAb Hanlikang® (Henlius rituximab biosimilar HLX01 to MabThera®) and trastuzumab biosimilar HLX02 to Herceptin® will be presented and discussed.

Monoclonal antibodies are a rapidly growing class of therapeutic molecules in biopharmaceuticals. Understanding the impact of glycosylation and close monitoring is critical for monoclonal antibodies development as a therapeutic molecule. This presentation will highlight the influence of different glycan variants on the drug’s behaviour inside the body and draw attention to commonly employed analytical techniques to determine and quantify glycan composition, structure, and glycosylation site.

As autologous gene therapy programs reach late clinical and commercial stages, the vector manufacturing process must scale to meet increasing demand. Process changes needed for improved performance and scale-up require thorough evaluation of analytical comparability to ensure that vector continues to meet quality standards once changes are implemented. We will discuss an industry perspective on the strategy for assessing analytical comparability and review some examples.

The control strategy for biologic products requires identifying the CQAs that impact efficacy and safety of the product. Traditionally, CQA assessment for comparability required the knowledge of process history, control strategy and clinical experience. To successfully demonstrate comparability for new/novel modalities, the risk assessment should evaluate the type/extent of process change and its impact to CQAs that affect efficacy and safety of the product.