Analytical

HCP Assay Development: Managing Risks with Evolving Technologies

Host-cell proteins (HCPs) are major impurities of concern in biomanufacturing. When present in drug formulations, they can reduce efficacy (by compromising product stability), introduce toxicity, and increase a recipient’s risk for long-term immunogenicity. Understanding HCP profiles and integrating effective removal strategies are important parts of developing new biological drugs — to fulfill regulatory guidelines and to ensure patient safety through product quality. HCP populations can be both complex and structurally diverse, and some changes in upstream culture conditions can affect…

Stability Testing: Monitoring Biological Product Quality Over Time

Many physical and chemical factors can affect the quality, safety, and efficacy of biopharmaceutical products, particularly after long-term storage in a container–closure system that can be subject to variations in temperature and light, as well as agitation with shipping and handling. Proteins are inherently complex physiochemically, from their primary amino acid sequences to their higher-order structures, and they require specific conditions to maintain their integrity and functionality. Advanced biological therapies can be even more complicated and particular about their environments.…

Emerging Strategies for Drug Product Comparability and Process Validation: Part 1 — Analytical Tools and Drug Product Comparability

Process validation is a key part of the development and manufacture of all approved drug products, but its completion can be a daunting task. At a two-day CASSS CMC Strategy Forum held in July 2016 in Gaithersburg, MD, speakers and attendees addressed the many technical, practical, and regulatory facets of drug product process validation and comparability. In part 1 of this report, we summarize the key discussion points of the first day, which focused on analytics and comparability. Session One:…

Customized Yeast HCP Quantification with Biolayer Interferometry Using a Horseradish Peroxidase Substrate

Biopharmaceuticals are the largest group of drugs under development (1), and the demand for new and safe drug products is high. The most common bacterial and mammalian cell lines for production are Escherichia coli, Chinese hamster ovary (CHO) cells, and yeast. During a production bioprocess, a cell line expresses not only the molecule of interest, but also host-cell proteins (HCPs). They are considered to be impurities in a final drug product because they can affect the efficacy and safety of…

Improving Cell Manufacturing Outcomes Using In-Line Biomarker Monitoring

Cell-based advanced therapies are changing modern medicine dramatically. Immunotherapies such as chimeric antigen receptor (CAR) T-cell therapies are treating different forms of cancer. Gene therapies are reversing the course of inherited diseases, and tissue-engineered medical products are restoring, maintaining, and replacing damaged organs (1–4). The development of new advanced therapies is booming. As of January 2020, the US Food and Drug Administration (FDA) has reported more than 900 investigational new drug (IND) applications for cell and gene therapy products. However,…

Using Prior Knowledge to Estimate Long-Term Variation

A reasonable estimate of long-term variation for a biopharmaceutical product critical quality attribute (CQA) can be challenging to justify, especially in the early stages of a product’s lifecycle when only limited data are available. However, if the combination of product and analytical method reasonably can be matched with historical data, prior knowledge can provide an estimate of a value. This variation estimate could be used to assist in risk assessments related to continued process verification (CPV) activities, including control charting…

Advanced Analytics to Accelerate Development of Genetic Vaccines

Biopharmaceutical companies are racing to develop vaccines that mitigate the COVID-19 pandemic, taking a wide range of vaccine-development approaches that include traditional modalities and cutting-edge technologies based on DNA and RNA. Vaccine developers are leveraging robust manufacturing concepts and integrated processes to shorten timelines. Advanced analytics also are playing a critical role in ensuring the safety and efficacy of those emerging vaccines. A New Wave of Vaccines Vaccines based on attenuated viruses entail development timelines ranging from four years to…

A Universal Assay Determination Method for Antisense Oligonucleotides: A New Slope Spectroscopy Method

Antisense oligonucleotides (ASOs) are short, synthetic, single-stranded oligodeoxynucleotides that can alter RNA and reduce, restore, or modify protein expression through several distinct mechanisms. ASO technology has become an important drug discovery platform for most major pharmaceutical companies. To date, six antisense drugs have been approved by regulatory agencies to treat diseases spanning viral infections, hyperlipidemias, and neurological diseases. More than 50 additional ASO drugs are in clinical trials. For an ASO drug product, an assay of its active pharmaceutical ingredient…

eBook: Biomarkers — Improving Clinical Studies to Enhance Commercial Success for Biologics

The biopharmaceutical industry continues to invest heavily in technologies for identification of predictive biomarkers. Drug developers want not only to find quantitative evidence that their therapies will work as designed, but also to anticipate which patient populations will respond positively to those regimens. Doing that could streamline clinical trials, accelerate approvals, and ultimately improve patient outcomes. Advances in next-generation sequencing and increases in computational capability now are facilitating biomarker inquiries, especially in the realm of immunooncology. However, predictive biomarkers remain…

Making Safe and Effective CAR T Cells: How Droplet Digital PCR Can Improve Their Quality Control

Chimeric antigen receptor (CAR) T cells first entered US clinics in 2017 (1), and this therapeutic modality holds tremendous potential as one of the most effective forms of personalized cancer care ever to reach patients. The revolutionary impact of CAR T-cell therapy comes from its ability to rewire our own immune defenses to kill cancer cells: It essentially modifies a patient’s naturally existing immune cells to boost their recognition and attack of cancer cells so that the person’s own immune system…