By the time you read this, I will have served as an award presenter for the first time. Even though it means dressing up and trying not to trip over myself on stage, I’m excited to do this, especially because the award I’ll be presenting at Biotech Week Boston is for sustainability initiatives. As a hiker, camper, gardener, horsewoman, and proud Oregonian, I hold environmental issues close to my heart. And sustainability is a major focus of our company too. BPI is printed on PEFC-certified paper sourced from sustainably maintained forestry.
The runners-up in this year’s BWB Awards sustainability category share such values. Cyclups Plantastiq (
https://www.cyclups.com
) specializes in compostable wheat-based packaging materials. Contract manufacturer RoslinCT (
https://www.roslinct.com
) is minimizing all scope 1, 2, and 3 greenhouse-gas emissions, using renewable energy, and reducing overall climate impacts. And Synterex (
https://synterex.com
) is a woman- and disability-owned clinical and regulatory con...
The biopharmaceutical landscape is marked by continuous advancements, breakthrough discoveries, and relentless pursuit of new targeted treatments. But underlying the call for transformative treatments is the vital importance of accurately assessing how new pharmaceutical interventions affect patient health and wellbeing. Despite significant progress in comprehending complex diseases, the current approach to biomarker development remains simplistic, fragmented, and “linear.”
Consider how clinicians usually determine whether to treat a cancer patient with an immune-checkpoint inhibitor — e.g., an antibody to programmed cell-death protein 1 (PD-1) or its associated ligand (PD-L1). The basic assumption is that if a drug targets PD-L1, then measuring PD-L1 levels in a tissue sample will indicate whether a patient will benefit from that drug. The same logic has been applied to cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3) proteins, and T-cell immunoreceptors with imm...
Research and clinical trials of cell/gene therapies (CGTs) have expanded greatly in recent years, and this area of the biopharmaceutical industry is showing no signs of slowing down. As of 2024, ClinicalTrials.gov in the United States lists more than 1,200 registered and active studies involving CGTs — a natural progression from a projection made by the US Food and Drug Administration (FDA) in 2019 (
1
). Before the global pandemic, the agency had predicted that by 2025, it would be approving 10–20 new CGT products every year. However, the industry has a long way to go before it will reach such a steady pace of approvals for these advanced therapies. As of 26 April 2024, the FDA had approved a total of 37 CGT products, including only seven in 2023 (
2, 3
).
We believe that early estimates did not account for some barriers to introducing new CGTs, including talent shortages, infrastructure growing pains, and outmoded technologies. However, the industry is making progress in those areas and turning its atte...
Laboratory and facility relocations often signal growth and progress for organizations. However, many lack the internal technical and relocation expertise necessary for a seamless move, which is crucial to minimizing downtime and preventing disruptions to daily operations and research activities. That situation underscores the importance of engaging experienced relocation engineers and technical project managers whose expertise can enhance operational efficiency significantly during transitions to new laboratory facilities. Such experts have provided support to hundreds of life-science organizations by developing and executing their laboratory-relocation plans. Whether driven by capacity constraints, the need for expanded research activities, and/or compliance demands, such experts can give guidance through every phase of the process. Herein, I explore key strategies for maximizing efficiency within a laboratory-relocation plan.
When an organization is ready to invest in a new laboratory facility to advan...
A scientist assesses virus-filter integrity using a bubble-point test method.
PHOTO COURTESY OF MILLIPORESIGMA (
HTTPS://MILLIPORESIGMA.COM
)
Estimating pinhole defects in large-scale membrane filters used during manufacturing is both a critical element of viral safety and a significant challenge, particularly for virus filters in large-scale multiround housings. Understanding the correlations among virus-filter structure, filter throughput, hydraulic permeability, and virus-clearance capacity is important for efficient process design and assurance of viral safety. Filter integrity tests (FITs) measure flow or pressure drops across wetted filters. Tests based on forward-flow diffusion often are used to assess virus-filter integrity for biomanufacturing applications (
1–4
). A pressurized gas, typically air or nitrogen, on the upstream side of the membrane provides a driving force for diffusion across a wetted membrane. Results from such testing enable detection of defects and gross leaks in individual fi...
+3Bioproduction technologies have revolutionized medicine, enabling the development of vaccines, cell and gene therapies (CGTs), and other biologics that hold promise for treating many diseases. Such modalities represent a dynamic, evolving pharmaceutical industry sector, and ensuring their safety and efficacy is crucial. Regulatory authorities and biopharmaceutical companies continuously seek to improve methods for detecting and identifying pathogens and other impurities in biotherapeutic products so that they can be safely inactivated or removed before administration to patients (
1
).
Integrating multiple testing methods into bioproduction ensures comprehensive product-quality and safety evaluation. Rigorous testing protocols must be used to determine that the products are free of bacterial, fungal, mycoplasma, and viral contamination; bacterial endotoxins; and residual host cell DNA and proteins. Such tests serve as critical checkpoints throughout manufacturing processes, guaranteeing the quality and sa...
Previous installments of this series throughout 2024 have discussed the basics of bioreactor scaling, mixing, and rates of oxygen uptake and mass transfer, along with the most commonly applied dynamic method for mass-transfer measurement. This month, part 4 continues the discussion of the volumetric mass-transfer coefficient (
k
L
a
) by showing how different culture and bioreactor operating parameters can affect its value. The next installment of this series will begin 2025 by presenting some theoretical correlations described in published literature that are used to determine
k
L
a
and often used in bioreactor scale-up exercises.
(see
The Series So Far box
).
Bioreactors are used for suspension-culture–based manufacture of most modern biopharmaceuticals. In such processes, oxygen is a key nutrient for cell growth, culture maintenance, and protein production. The typical oxygen uptake rate value for mammalian cell cultures at a concentration of ≈10
6
cells/mL is 0.05–1.5 mmol O
2
per liter of cultur...
Perfusion is being explored as a viable option for upstream-process intensification. Research on such intensification concerns increased productivity and decreased production costs and time; therefore, perfusion, as a continuous addition of fresh media and removal of used media, could reduce the burden on upstream processes. However, scalability remains challenging. Geometric similarity between laboratory-scale and production-scale bioreactors often is considered. In fully turbulent conditions, bioreactor shape, volumetric power input (
P/V
), fluid profile, and power-input distribution should be consistent at all scales. In an April 2024 Ask the Expert webinar, Jan Ott (research associate at the Zurich University of Applied Sciences (ZHAW) School of Life Sciences and Facility Management) presented with support from Repligen about scaling perfusion processes based on novel bioreactor technologies, such as single-use vessels.
The heart of each perfusion process is the cell-retention device. Such devices us...
This article discusses the increasing reliance of biopharmaceutical drug innovators on contract development and manufacturing organizations (CDMOs) as the market evolves and continues to grow. The work of CDMOs allows major pharmaceutical companies to outsource parts of their business, enabling them to scale their manufacturing and focus on drug discovery and delivery. The article emphasizes the importance of CDMOs focusing on their core mission to develop and manufacture drugs for their clients, while seeking cost-effective solutions for non-core activities leading up to the core production jobs.
The article suggests that by partnering with industry experts, CDMOs can streamline their workflows, resulting in greater efficiencies, lower operational costs, and avoidance of capital expenditures. It provides an example of such a partnership in the area of supply chain management, where a distribution partner can perform critical jobs, maintain inventory of critical materials, and provide just-in-time deliver...
Impurity characterization of biopharmaceuticals is changing. Health authorities increasingly require orthogonal data to support enzyme-linked immunosorbent assays (ELISAs), pushing for thorough, reliable documentation of downstream purification to reduce process-related impurities such as host-cell proteins (HCPs). With the upcoming US Pharmacopeia (USP) General Chapter <1132.1> on HCP measurement by liquid chromatography–mass spectrometry (LC-MS), LC-MS is set to become an essential method for identifying and quantifying protein impurities, offering the levels of detail and coverage that ELISA lacks.
Thomas Kofoed of Alphalyse, a contract research organization (CRO) specializing in LC-MS–based HCP analysis, interviewed three chemistry, manufacturing, and control (CMC) specialists about current and future applications of LC-MS for impurity analysis in the biopharmaceutical industry. The interviewees were Margarita Sabater of Genmab, Bryant McLaughlin of BCM Solutions, and Søren Skov Jensen of Genmab at th...
+2 Host cell proteins (HCPs) represent a major group of process-related impurities in biological drugs produced using cell-culture technology. Many HCPs are benign; but some are immunogenic, some may interact with a drug substance (DS), and others (e.g., proteases and lipases) can reduce effective product dosage (by acting directly on the drug or interfering with its formulation buffer and stability).
To monitor the effectiveness and consistency of downstream purification processes, biomanufacturers rely on HCP enzyme-linked immunosorbent assays (ELISAs). But even ELISAs have analytical limitations, necessitating orthogonal confirmation of their detection ability to detect HCPs. Biomanufacturers must ensure that a selected HCP ELISA method is fit for its intended use. Qualifying an ELISA involves determining its range and demonstrating sufficient dilutional linearity, accuracy, and precision. A factor that distinguishes HCP ELISAs is their requirement of HCP-antibody coverage assessment to ensure broad react...
+1 The small-molecule drug Relyvrio (sodium phenylbutyrate and taurursodiol) was one of the few approved medications for amyotrophic lateral sclerosis (ALS) before it was removed from the shelves in early 2024 after poor phase 3 results. ALS patients have few treatment options now, most of which merely manage the symptoms of the disease without preventing or treating it.
ALS is a rare disease, and in most cases, we don’t know what causes it. The ALS Association determined that about 90% of cases occur without any known family history or genetic cause (
1
). About 5000 people in the United States are diagnosed with ALS every year, and more than 20,000 Americans live with the disease.
Therapeutics for neurodegenerative diseases currently focus on managing symptoms and improving quality of life for patients. Although such outcomes are welcome, therapies are expensive and do little to improve life expectancy. Marketed therapies for ALS have shown advancements in reducing symptoms but not in curing disease.
For i...
