November-December 2023

From the Editor: November-December 2023

As I look forward to retirement and revisit 35 years in publishing, I marvel at all the adventures that a graduate degree in comparative literature can lead to. I’d always dabbled in biology, but for some years, literature, languages, and teaching won out. By the late 1980s, leaving a dissertation unfinished didn’t help me compete for full-time community college teaching gigs. Carpentry and school-bus driving were okay for a while, and playing baroque recorder music garnered extra grocery money, but…

Ensuring Data Integrity in GxP

Our world provides us with abundant data at every moment of every day that we constantly analyze to make decisions. What is most important in a business/laboratory context is that the data we receive be attributable, accurate, legible, permanent, contemporaneous, and original. A company’s pharmaceutical quality system (PQS) plays a vital role in analyzing data integrity. As explained in ISO/IEC 2382:2015, data describe formalized representations of information suitable for communication, interpretation, or processing (1). According to the same ISO standard,…

The Legacy and Future of Genomic Medicine: From the 15th Annual State of Personalized Medicine Address

The Personalized Medicine Coalition met in Washington, DC, in May 2023 to commemorate the 20th anniversary of the Human Genome Project’s completion. Eric Green, director of the National Human Genome Research Institute (NHGRI), has been a key contributor to the fields of genomics and personalized medicine for more than three decades. According to Lincoln Nadauld, cofounder and chief executive officer (CEO) of Culmination Bio, Green’s work has “included significant involvement in the Human Genome Project, during which he and his…

Accelerating Rare-Disease Drug Development: The Key Role of Patient Registries

In the United States, a rare disease is defined as a condition that affects fewer than 200,000 people nationwide. The World Health Organization defines a rare disease as a disorder that affects fewer than 65 per 100,000 people (1). In the European Union, the definition narrows to five in 10,000 people. Ten percent of the global population is affected by at least one of the >10,000 identified rare diseases — which accounts for about 30 million people in the United…

Using Automated Immunoassays for HCP Analysis in Early Bioprocess Development

Biopharmaceutical drugs are produced by a number of expression host systems, mainly mammalian (e.g., Chinese hamster ovary, CHO) and microbial (e.g., Escherichia coli) cells. The goal of subsequent purification steps is production of a pure drug substance, which is essentially free of product variants and process-related impurities such as host cell proteins (HCPs) and nucleic acids. Depending on the process, HCPs can represent the total proteome of a host cell line and accordingly are highly diverse in size, charge, hydrophobicity,…

Choosing Tolerance Intervals: A Framework To Use in Setting Specification Limits Based on Manufactured Drug Lot Data

As defined in ICH Q6A, a specification is a list of tests, references to analytical procedures, and appropriate acceptance criteria that take the form of numerical limits, ranges, or other criteria for the tests described (1). They establish the set of criteria to which a new drug substance or product should conform to be considered acceptable for its intended use. Ideally, specifications are established based on demonstration of quality attribute levels that make drugs safe and efficacious during toxicology and…

Identifying False Metabolite Measurements During Cell-Culture Monitoring Effective Application of the Multivariate Hotelling’s T2 Statistic

Upstream process scientists and engineers actively monitor bioreactor metabolite levels during cell culture using off-line blood-gas analyzers (BGAs) and related instrumentation. But such tools introduce inherent variability into metabolite measurements. The magnitude of that variability depends on the measurement range. Mammalian cells are sensitive to concentrations of one such metabolite: dissolved CO2. In cell cultures, CO2 levels often are reported as partial pressure (pCO2) in millimeters of mercury (mmHg). Available literature frequently reports that elevated pCO2 concentrations have adverse impacts…

Scalable mRNA Affinity Capture: Supporting Development and Production of mRNA-Based Therapeutics

As a direct result of the COVID-19 pandemic, mRNA-based therapeutics have made significant clinical and commercial progress. With many such therapeutics filling up the clinical pipeline for a growing number of indications, the biopharmaceutical industry is investigating efficient and scalable manufacturing techniques. For example, Thermo Fisher Scientific has developed a novel affinity chromatography resin with a poly(styrene-co-divinylbenzene) backbone and with throughpores to isolate and purify mRNA at various scales. Because the POROS Oligo dT(25) affinity resin binds mRNA through a…

Detection and Quantitation of Process-Related Impurities

Detection and quantitation of process-related impurities are important to quality control in biopharmaceutical manufacturing. Process-related impurities can have a significant impact on pharmaceutical product quality, safety, and efficacy. Such impurities can be generated during a biomanufacturing process and come from product degradation, starting materials and reagents, by-products, storage conditions, and contamination. Without proper detection and quantification, process-related impurities can cause adverse effects in patients. Guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)…

Creating Value As a CDMO

As a contract development and manufacturing organization (CDMO), Aton Biotech provides a comprehensive set of services to clients developing biological drugs. Those services range from cell line development to clinical development and end-to-end commercial manufacturing. A Long History Aton emerged from a biopharmaceutical company called Henlius that was established in Shanghai, China, nearly 13 years ago. Today, Henlius has five products on the market including rituximab, trastuzumab, and adalimumab. From the beginning, company leadership decided to build internal manufacturing capacity…