Analytical Archives - BioProcess InternationalBioProcess International

Continued Process Verification: A Multivariate, Data-Driven Modeling Application for Monitoring Raw Materials Used in Biopharmaceutical Manufacturing

by Hao Wei, John Mason and Konstantinos Spetsieris

Biologics manufacturing entails multiple complex unit operations across three key process areas: cell culture, purification, and sterile fill–finish (Figure 1). Numerous raw materials are used to formulate reagents that are vital to those processes. For example, bioreactors require cell-culture media, and buffer solutions are used during both drug-substance filtration and drug-product final formulation. Changes in raw-material properties can introduce variation in the performance of intermediate processes and in product quality attributes. Therefore, raw-material properties must be monitored to help ensure…

Specification Limits for Biomanufacturing Processes: Comparing Tolerance-Interval and Process-Capability Methods

by Naveenganesh Muralidharan

Critical quality attributes (CQAs) such as safety, efficacy, purity, and identity must be monitored and controlled in biopharmaceutical products to meet predefined specification limits. Setting such parameters is critical but challenging. Unduly narrow specification limits increase risks for rejecting good product batches, whereas overbroad limits can lead to acceptance of bad batches (1). Limited sample sizes, homogeneous results obtained from testing of raw materials exhibiting scant variability, and variability inherent to testing methodologies can add up, encouraging quality teams to…

Pharmaceutical Manufacturing Quality Assurance Programs: Transitioning from Research and Development to the Clinic

by Lauren Schoukroun-Barnes, Dianne Cantara, Sarah DeDonder and Dawn Speidel

On average it can take or even exceed US$1 billion to get a pharmaceutical product to market, and nine out of 10 products developed never make it to commercialization (1). As technology advances, more potential therapies and preventatives are being developed and optimized by virtual companies. They are typically small, newly formed organizations that build their momentum on programs for novel products. Because many of the program activities are outsourced, virtual start-up companies developing pharmaceutical products raise concerns about ensuring…

Process Validation: Calculating the Necessary Number of Process Performance Qualification Runs

by Naveenganesh Muralidharan

The 2011 process validation (PV) guidance document from the US Food and Drug Administration (FDA) states that the number of samples used for PV “should be adequate to provide sufficient statistical confidence of quality both within a batch and between batches. The confidence level selected can be based on risk analysis as it relates to the particular attribute under examination” (1). In alignment with those expectations, I present herein two statistical methodologies for calculating the necessary number of process performance…

Building the Next Generation of Cell-Line–Development Platforms

by Lisa Blaschke, Catherine Krikelis, Joel Watkinson and Katy McLaughlin

Speed to market is a critical business driver in the biopharmaceutical industry. However, drug development success also requires building a robust process that maximizes efficiency while limiting the cost of goods. Achieving time and cost savings without compromising product quality is critical. Development of a productive and stable cell line is the foundation of an efficient and high-performing bioprocess. Cell-line development (CLD) represents some of the most resource-intensive steps within a process development pipeline. Bioprocess scientists must find a balance…

Targeting RNA: How Epitranscriptomics Can Improve Productivity

by Cheryl Scott, with Niall Barron

Cell-line development traditionally has focused on genetic engineering of chromosomal DNA in cellular nuclei. Combining technological advances such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) with ever-increasing genomic knowledge has enabled scientists to get impressive performance from microbial, plant, and animal cells. But few researchers have considered the potential for manipulating how genes are transcribed as an avenue for increasing productivity — until recently, that is. Niall Barron is a professor of biochemical engineering at Ireland’s National…

A Case Study in Environmental Monitoring: Reviewing Incubation Times Upon Recovery of Microorganisms

by Tim Sandle

Environmental monitoring (EM) remains an essential detection tool for cleanrooms within healthcare and pharmaceutical-manufacturing facilities. During monitoring, an agar growth medium is incubated at a specific temperature for a set time. There is no single approach to incubation. Researchers have performed several EM incubation studies, with results reflecting a diversity of practice. Typically, biomanufacturing sites either run selective monitoring sessions using single-incubation regimes with two different culture media, or they leverage a dual-incubation system using two temperature ranges with a…

Water-Proton Nuclear Magnetic Resonance Spectroscopy: Emerging Applications for Vaccine Quality Assessment

by Brian Gazaille, with Marc B. Taraban

Liquid-formulation vaccines often require shipment and storage within a temperature-controlled supply chain (a cold chain) between manufacture and administration. Since 2020, mRNA vaccines against SARS-CoV-2 have received considerable attention for their extreme cold-chain specifications. For instance, Pfizer–BioNTech’s Comirnaty bivalent booster for adults and adolescents must be stored in specialized freezers set between –90 C and –60 C for as long as 18 months (1). Usually, however, vaccines are shipped and stored in conditions between 2 C and 8 C (the…

Opportunities in the Field of Host Cell Proteins — Part 4: The Future of Immunogenicity Prediction

by Victor Pérez Medina Martínez, Carlos Eduardo Espinosa-de la Garza and Néstor O. Pérez

Available literature abounds with case studies describing detection and identification of host cell proteins (HCPs) and other process-related impurities. In the previous installment of our review, we analyzed noteworthy studies, highlighting what they revealed about HCP immunogenicity and calling attention to topics that require further investigation. In this final installment of our four-part study, we focus on HCP risk assessment. We explore current and emerging strategies for immunogenicity prediction, then draw out key insights from the past 40 years of…

Real-Time, Data-Driven, and Predictive Modeling: Accelerating Digital Transformation in Drug Substance Commercial Manufacturing

by Pablo J. Rosado, Badua Merheb and Alejandro Toro

Biopharmaceutical drug-substance (DS) manufacturing consists of several unit operations. Upstream production includes multiple steps in growing bacterial or mammalian cells in culture. Upstream activities are followed by a series of downstream processing units including chromatography and filtration steps for removing impurities and purifying a therapeutic molecule (1). All these operations are inherently complex because of the natural variability associated with growing living cells and the intricacy of purification techniques used for collecting biological products. The US Food and Drug Administration…