Process Monitoring and Controls Archives - BioProcess InternationalBioProcess International

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…

Cleaning Validation Acceptance Limits for Biological Process Residues: Part 1 — Acceptable Exposure of Degraded Proteins Based on Reference Immunogens

by Rizwan Sharnez, Andrew Brewer, Darragh Halpin, Ina Hammond, Jeffery Felker, Kathleen Bellorado-Kendrick, Laura Goldberg, Loleta Chung, Maria Delgado-Rentas, Mary Gibson, Michael Parks, Paul Hefner, Rajyalakshmi (Raji) Vathyam, Sushil Abraham, Timothy Riehlman, Xiaona Wen and Yunjuan (Jane) Wang

Over the past decade, human therapeutic proteins (HTPs) have become far more potent, and consequently, their acceptable exposures have decreased substantially. That has led to commensurately lower acceptance limits for biological process residues. Simultaneously, host-cell and other protein concentrations have increased considerably, thereby making process equipment potentially more difficult to clean. These trends have made biopharmaceutical cleaning validation more challenging. For example, the acceptance limits for many HTPs — based on acceptable exposures of active proteins — are on the…

eBook: Bioprocess Monitoring — Still on the Path to Dynamic Control

by Brian Gazaille

The biopharmaceutical industry agrees that process analytical technologies (PATs) and automation will improve process consistency, enhance biologic quality, reduce production costs, and accelerate workflows. However, technologies for on- and in-line bioprocess monitoring generally remain in process development laboratories rather than being used on the manufacturing floor. Some difficulties stem from limitations with current sensing methods and technologies. Other problems relate to implementation and integration of existing information-technology (IT) solutions. And still other concerns arise when company leaders need to make…

Tangential-Flow Filtration Process Control and Data Acquisition System for Process Development

by Mahesh Khot

PendoTECH tangential-flow filtration (TFF) process control systems have been widely adopted in the filtration community. The system’s features enable its implementation in multiple unit operations and biopharmaceutical processing applications, including ultrafiltration–diafiltration (UF–DF) of proteins, viruses, and compounds such as oligonucleotides and antibody–drug conjugates (ADCs). The control system can be used to develop process parameters for UF–DF processes that have different membrane formats (e.g., flat-sheet cassette and hollow fiber). TFF laboratory setups often are manual or semiautomated processes that use pumps,…

Statistical Method for Establishing Control Limits for Nonnormal Data Distribution: Focus on Continued Process Verification Monitoring

by Naveenganesh Muralidharan

According to the US Food and Drug Administration’s (FDA’s) process validation guidance, critical quality attributes (CQAs) and critical process parameters (CPPs) are used to assess the statistical stability of a bioprocess and its ability to meet acceptable criteria as a part of a continued process verification (CPV) program using control charts (1). For those control charts, control limits are used to assess the statistical stability of process parameters and attributes. When data are normally distributed, control limits are established straightforwardly…

Innovations in Cell Culture, Sensor Technology, and Process Control: Preparing for Industry 4.0

by Jim Furey

To celebrate the 20th anniversary of BioProcess International, industry suppliers were asked to respond to a questionnaire about the important technologies, trends, and manufacturing innovations that have shaaped their companies and the entire industry over the past two decades. What has been the most important scientific or technological innovation in the past 20 years of bioprocessing? I have been in the industry since the mid-1990s, and clearly the most significant evolution in biomanufacturing has been the widespread implementation of single-use…

Bioprocess Monitoring and Control: New and Continuing Needs in the Biopharmaceutical Industry

by Nick Pittman and Magnus Wetterhall

Equipment vendors, technology developers, and service providers have played an integral role in promoting innovation in the biopharmaceutical industry, from upstream production to final packaging and distribution of biological products. To enrich our understanding of the past 20 years of bioprocessing, BPI distributed questions to supplier companies. Below, Nick Pittman and Magnus Wetterhall of Waters Corporation reflect on advances in — and remaining opportunities for — process analytical technologies (PATs). What Innovations Have Been Most Formative to the Past 20…

Process Intelligence: Gene Therapy Case Study Shows That the Journey to Improved Capabilities Starts with One Step

by Dermot McCaul

The product development team at a gene therapy contract development and manufacturing organization (CDMO) was working on a high-priority drug-substance project for a key client. The material was crucial to that client’s early stage clinical trial, with an immediate value over US$500,000 to both the client and the CDMO. Unfortunately, the bioreactor used in the upstream process — a transfection unit operation for an adenoassociated virus (AAV) vector — had developed an intermittent problem that could force it to shut…

Automated Process Control Based on In Situ Measured Glucose Concentration

by Silvia Sturzenegger

A process analytical technology (PAT) strategy involves defining critical process parameters (CPPs) of a biomanufacturing process that influence critical quality attributes (CQAs) and controlling those CPPs within defined limits. Doing that enables consistent product quality and helps companies reduce waste and costs. Glucose is an important CPP in bioprocessing and cell therapy. Glucose often is fed as a bolus addition based on daily off-line measurements, but that can lead to high glucose fluctuations and to excessive glucose feeding, which can…

Seamless Integration of Glucose Control: Using Raman Spectroscopy in CHO Cell Culture

by Célia Sanchez, Laure Pétillot, Fabrice Thomas and Charlotte Javalet

The process analytical technology (PAT) and quality by design (QbD) guidelines promoted by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) support the idea that quality cannot be “tested into” a biologic product but must instead be part of its process design. Seamless integration of analytical data with bioprocess monitoring and control is crucial to understanding a process and overcoming manufacturing challenges that arise in the course of development. Monitoring of product quality attributes (PQAs)…