Lentiviral vectors (LVVs) are broadly used in research and therapeutic development, yet substantial interlaboratory variability continues to hinder the comparison of vector quantity, potency, and impurity measurements, underscoring the need for standardized reference materials. To address this need, the Lentiviral Vector Reference Material (LVVRM) initiative was launched as a structured, multi-phase effort, with earlier phases focused on large-scale upstream production and downstream preparation of a GFP-encoding LVV. In the final phase of the LVVRM initiative described herein, bulk material produced during prior large-scale manufacturing runs was thawed, pooled, subjected to sterile filtration, and dispensed into single-use vials under controlled conditions designed to maintain stability and consistency. Each lot then underwent comprehensive quality control testing. Sterility, identity, purity, physical and functional titers, and safety attributes were assessed using established characterization frameworks appropriate for lentiviral vector reference materials. The resulting LVVRM (ATCC® VR-3382™) met quality standards and release criteria, providing a well-characterized reagent suitable for assay calibration, method qualification, and longitudinal performance monitoring across laboratories.
Tag: <span>quality control</span>
Contract testing organizations (CTOs) offer considerable value by providing testing services and expertise that may not be available within organizations that are developing and producing biopharmaceuticals, from virtual companies to fully integrated international organizations. CTOs are constantly challenged by the breadth of services that are requested as well as the levels of regulatory compliance that are expected and the degree of oversight that various companies intend to impose. And knowing this variability of needs and expectations often results in a CTO trying to become “all things to all people” regarding assay tech transfer, validation, and qualification. For example, with the same type of sample from the same stage of product development, one company may expect its contracted testing to comply with 21 CFR Part 210 and 211 (good manufacturing practice [GMP]) while another may expect its testing to comply with 21 CFR Part 58 (good laboratory practice [GLP]) with different assay validation expectations for each approach…
Automation in bioprocessing was a keynote topic at the ISBioTech 4th Annual Fall Meeting (December 12–14, 2016) in Virginia Beach, VA. Automation is becoming increasingly critical as biomanufacturers seek to improve their production efficiency and critical risk analysis, and reduce errors. But despite recent improvements and innovations, the actual integration of devices, software, sensors, and production equipment remains a challenge. In BioPlan Associates’ recent analysis of capacity and production, we found that nearly 20% of the biopharma industry sees increasing productivity and efficiency as the #1 critical issue the industry needs to focus on today. And over two-thirds expect better control of their processes. An obvious way to achieve these goals is through automation…
One of the objectives of the upcoming ICH 12: Pharmaceutical Lifecycle Management guidance is to manage product development and manufacturing process information in order to establish and maintain appropriate change control over the entire product lifecycle. The 2014 ICH Q12 Concept Paper also stresses ICH Q12’s role in connecting ICH Q8 through ICH Q11 into a complete lifecycle approach to assure product quality and continuous improvement of manufacturing operations. However, neither the Concept Paper or subsequent public discussion and presentations appear to identify the ICH Q8 design space as a central mechanism for collecting and maintaining product and process information…
Regulatory agencies routinely announce changes in the GMP (Good Manufacturing Practices) norms and quality standards designed to guarantee that every product retains characteristics required for its pharmaceutical use.The alignment with emerging regulatory requirements is mandatory, therefore, to assure production process consistency, as well as the safety and efficacy of the finished product…
One of the major concerns facing relatively young biotechnology companies once a lead product has been identified is the issue of manufacturing. Usually this involves the upscaling of a lab-scale process while at the same time, complying with good manufacturing practice (GMP) to ensure a reproducibly-produced and consistent product. It also involves the establishment of specific and robust assays in process controls and release criteria. This issue has become more acute in the EU since 2004 due to the EU Clinical Trials Directive requiring GMP-certified production of investigational medical products even for phase I trials. Startup biotech companies are often limited in their finances and resources, as well as being bound by tight milestones. Quite often the expertise in upscaling and GMP-compliant production as well as the facilities and equipment required are not available in-house…
Recombinant DNA-transduced cellular products encounter the product development and regulatory issues of both gene therapy and cellular therapy products. The characterization of recombinant DNA-transduced cellular products remains highly challenging for both sponsors and regulatory agencies. The regulatory concerns and product testing for such cellular products are similar to those for all biologicals. These concerns include the demonstration of product safety, identity, purity, and potency; the control of the manufacturing process to ensure the consistency of product manufacturing under a proper quality control program; and the demonstration of reproducibility and consistency of product lots by means of defined product lot release testing criteria…
A program for control of biopharmaceutical raw materials is a critical quality system that helps assure patient safety and contributes to product quality. The systems for testing and acceptance must be scientifically based, and meet global regulatory requirements and standards. When a new raw material is sourced, it is important to quickly establish the quality profiles for the supplier and the raw material. Among the numerous challenges that confront a company attempting to establish an effective, compliant, raw materials program, this paper will address the following: • Challenges in sourcing and tracing raw materials that are suitable for use in human therapeutics • Challenges and obstacles in qualifying suppliers • Special challenges faced by a firm that has outsourced its manufacturing and/or quality control (QC) testing…
Polysorbate-80, or polysorbitan mono-oleate, a non-ionic surfactant commercially referred to as Tween-80, is commonly employed as an excipient in the biopharmaceutical industry due to its low toxicity as well as its ability to solubilize hydrophobic molecules. Thus, polysorbate-80 is employed as a stabilizer in order to control the formation of protein aggregates and larger particulates in biopharmaceutical drug substance and drug product formulations. Guidelines published by The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and the United States Pharmacopeia (USP) classify excipients such as polysorbate-80 as major components in biopharmaceutical formulations and specify that these types of compounds be quantified using a validated analytical method…
The Dale and Betty Bumpers Vaccine Research Center (VRC) at the National Institutes of Health (NIH) was established to facilitate research in vaccine development. The VRC is dedicated to improving global human health through the rigorous pursuit of effective vaccines for human diseases. It was established by former president Bill Clinton as part of an initiative to help develop an AIDS vaccine and is part of the NIAID organization. Since the inception of the VRC, its mission has expanded to include the development of vaccines against bioterrorism and emerging infectious diseases…