QA/QC

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

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…

The Future of Virtual Audits and Audit Success

Audits are a vital quality-management tool in the biopharmaceutical industry. Whether the activity is verifying supplier or partner qualifications, contributing to corrective and preventative actions (CAPAs), or fulfilling regulatory requirements, proactive auditing is key to successful operations. Over the past couple of years, virtual audits — also known as remote or distance audits — have enabled biopharmaceutical companies to maintain compliance and quality-assurance (QA) demands despite COVID-19–related travel restrictions and social-distancing protocols. Now that the world is opening up again,…

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

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…

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

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…

eBook: BPI Lab — Patterns, Peaks, and Trends: Advantages of Digital Data for Biopharmaceutical Quality Control

Socrates said the unexamined life is not worth living. Similarly, data are useless without analysis. And even as artificial intelligence makes inroads into the biopharmaceutical industry, human insight remains important. Graphically representing data is more than just creating pretty pictures; proper data visualization can improve the communication of sometimes abstract information to make data accessible, understandable, and usable. Patterns and insights arise during the review process — whether data are intended for internal or external publication or for inclusion in…

Quantitative Risk Assessment of Limits for Residual Host-Cell DNA: Ensuring Patient Safety for In Vitro Gene Therapies Produced Using Human-Derived Cell Lines

Viral-vector gene therapies (GTs) manufactured from cell-substrate production systems can contain residual amounts of host-cell DNA (hcDNA), which in a final product presents safety risks to treated patients. Therefore, drug manufacturers monitor and control residual hcDNA levels in purified products (1, 2). The US Food and Drug Administration (FDA) and other global regulatory agencies recommend tight, quantifiable limits for hcDNA levels: 10 ng/dose, with DNA fragments smaller than the functional gene size of 200 base pairs (bp) (3). However, because…

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

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…

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

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…

The State of Quality Risk Management in the Pharmaceutical Industry: Commentary on the Draft ICH Q9 Revision

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) released a long-awaited draft revision of its Q9 guidance on quality risk management (QRM) for public consultation in December 2021 (1). First published in 2005, ICH Q9 has been instrumental in highlighting the importance of QRM in both the small- and large-molecule pharmaceutical industries. It was the first comprehensive guidance to explain how QRM could be used to identify, assess, and control risks to drug-product quality…

Container Materials for Biopharmaceuticals: A Comparative Small-Scale Case Study of Stainless Steel and a Proprietary Nickel-Based Alloy

Evaluating compatibility of a drug substance with all surfaces that it might come into contact with during drug product manufacturing is essential to ensure product quality. Proteins can adsorb to contact surfaces, form aggregates, and desorb into a drug-substance solution. Proteins also can degrade in presence of leachables generated from contact surfaces during manufacturing. Containers and vessels used during manufacturing are single-use disposable components or metal tanks, primarily either 316L stainless steel (SS) or C-276 Hastelloy nickel-based alloy (HLY). Researchers…