Analytical

Points to Consider in Quality Control Method Validation and Transfer

The concept of an analytical lifecycle has been well received in the biopharmaceutical industry. In 2016, the US Pharmacopeia (USP) advocated for lifecycle management of analytical procedures (1) and defined its three stages: method design development and understanding, qualification of the method procedure, and procedure performance verification. The US Food and Drug Administration (FDA) has published guidance on process validation with a similar division into three stages: process design, process performance qualification, and process performance verification (2). For a manufacturing…

Apparent Matrix Effects in an Iduronate 2-Sulfatase Specific Activity Assay

The recombinant fusion protein SHP631 consists of a chimeric monoclonal antibody binding to human insulin receptor and iduronate-2-sulfatase (I2S). This product is being developed as an enzyme replacement therapy to treat cognitive symptoms of Hunter’s syndrome. Because the current therapy (idursulfase, brand name Elaprase from Shire) cannot cross the blood–brain barrier (BBB), SHP631 is being developed to do so, enabling the presence of I2S in the brain. The enzymatic activity of this molecule is measured using the substrate 4-methyl umbelliferyl-α-L-idopyranosiduronic…

Developing an End-to-End Scale-Down Model for a Commercial-Scale Downstream Process: Enhancing Technology Transfer Efficiency

Large and complex protein molecules used as therapeutic agents are manufactured in a series of process steps that start with thawing of cell-bank vials and finish with filling and packaging (Figure 1). The cost and complexity of commercial-scale biomanufacturing processes make them prohibitive to troubleshoot or experiment at full commercial scale. Biopharmaceutical companies routinely use scale-down models (SDMs) of licensed commercial-scale processes to evaluate raw material changes, process improvements, and deviations (1) (Figure 2). Here, we outline some considerations in…

Continuous Chromatography: Experts Weigh in on the Possibilities and the Reality

Discussions of continuous processing in the biopharmaceutical industry are an important part of current efforts toward intensifying bioproduction and bioprocessing. Biomanufacturers are looking at all components of their development and manufacturing processes for ways to reduce the size of their facilities, lower costs, and increase speed and flexibility of operations. Increasing options for and availability of single-use technologies have been major enablers of myriad attempts to improve efficiencies. Although the general consensus may still be that single-use components are more…

Aspects of Acceleration: Biomanufacturers Need Smart Strategies to Speed Products to Market

No matter what the industry, it’s widely accepted that slow-moving companies give their nimbler competitors an advantage, allowing them room to dominate the market even if their products are not superior. “Me-too” products and their sponsors often are seen as followers rather than leaders — even if they offer improvements over what is already available. Fast movers are flexible and adaptive to a dynamic business environment. They capitalize on opportunities and navigate risks and challenges by responding quickly to changes…

Qualitative and Quantitative Host Cell Protein Analysis Using Mass Spectrometry

Host cell proteins (HCPs) originate from host organisms that are used to produce biopharmaceutical products. They are in-process contaminants that must be minimized during downstream process operations. According to regulatory agencies, the maximum permitted level of total HCP in a biopharmaceutical product is 100 ng per mg (100 ppm) (1). HCPs can decrease drug efficacy and pose a risk to patient safety because they can bring on undesirable immune responses. Thus, HCPs are a critical quality attribute that should be…

Using Slope Spectroscopy Methods: Risk Assessment and Cost Savings

The biopharmaceutical industry’s need for rapid, accurate concentration measurements of protein-containing products is critical. The protein-concentration assay measures ultraviolet absorption at 280 nm (A280) and usually is performed both as an in-process test and for product-release testing. The SoloVPE system can analyze samples across a wide range of target concentrations without the need for labor-intensive and error-prone dilutions. Slope Spectroscopy methods provide companies with a universal platform for determining protein concentration for all in-process, clinical, and commercial methods. During in-process UV…

The Changing Landscape of Single Use in Bioprocessing: An Interview with Stefan Schlack and Jean-Marc Cappia

Single use in bioprocessing has changed significantly in recent years. To find out how a leading supplier to the biopharmaceutical industry is redefining its technology to align with new market challenges, science writer, Sue Pearson, had the opportunity to interview Stefan Schlack, Head of Bioprocess Marketing, and Jean-Marc Cappia, Head of Segment Marketing Vaccines, both at Sartorius Stedim Biotech (SSB) in Goettingen, Germany. Redefining Single Use Pearson: Sartorius Stedim Biotech is a recognized leader in single-use technology, and you’ve recently…

Biosimilars: Challenging the Justifications for Clinical Testing

The Biologics Price Competition and Innovation Act (BPIA) of 2009, describes the need for clinical trials as follows (1): “(cc) a clinical study or studies (including the assessment of immunogenicity and pharmacokinetics or pharmacodynamics) that are sufficient to demonstrate safety, purity, and potency in one or more appropriate conditions of use for which the reference product is licensed and intended to be used and for which licensure is sought for the biological product.” However, all the above studies are left…

Development and Biomanufacturing Strategies for Next-Generation Antibody-Drug Conjugates

The development and manufacture of antibody-drug conjugates (ADCs) requires a series of complex steps. ADC manufacturers must comply with guidelines for both the small-molecule linker-drug and the monoclonal antibody (MAb). The authors describe their company’s development of its lead ADC product. They review process decisions, including the issues that factored into their selection of single-use systems, manufacturing challenges (differences between ADCs and MAbs), and testing methodologies for extractables and leachables. Synthon began as a small-molecule generics company in 1991. During…