June 2024

Technology transfer is a sophisticated and complex undertaking that requires careful planning to ensure successful transition and regulatory compliance. The biopharmaceutical industry is concerned with two main types of technology transfer: scale-up and transfer to a different site ( 1, 2 ). Scale-up technology transfer often occurs within an organization or facility and involves moving a technology or process from a laboratory or pilot-scale environment to a larger manufacturing scale. Such work can help to increase production capacity, improve efficiency, and optimize technology for commercialization. Transfer to a different site involves relocating a technology or process from one location or organization to another. This type of transfer often is undertaken when a company wants to replicate or implement a technology at a new facility, either within the same organization or internationally. This article focuses primarily on the considerations that organizations should make when conducting technology...

The integration of digital collaboration platforms into research and development (R&D) workflows is transforming life sciences. By automating data management and leveraging cloud computing’s scalability, companies can achieve groundbreaking advancements in predictive modeling and drug discovery, easing the process of bringing therapies to market. Such digital infrastructure not only fosters a collaborative global network, but also aids in regulatory compliance and traceability across all R&D processes. Below, we explore the multifaceted layers of digital-collaboration platforms (e.g., the LifeSphere platform by ArisGlobal, Benchling, and Synthace) that assist with evidence-based medical breakthroughs. Support for Biopharmaceutical R&D Developing a new drug requires a long lead time and significant financial investment, with little chance for success ( 1 ). To bring therapies to clinics faster and reduce prices for patients, the biopharmaceutical industry is increasing R&D efficiency by integrating new tec...

The tides of change have reached the banks of cell and gene therapy (CGT) manufacturing, washing ashore new concepts and capabilities that are inspiring the industry to rethink traditional business practices. During the relatively short history of CGT manufacturing, drug-sponsor companies and contract development manufacturing organizations (CDMOs) have changed their business expectations, operating models, and partnership dialogues. CGT developers no longer ask themselves whether they want to partner with a CDMO, but instead must consider when and how they want to do it. During the first years of the CGT boom, companies often built their own manufacturing facilities to ensure capacity because the market lacked alternatives. But recently, some companies have sold their in-house manufacturing facilities and partnered with CDMOs to maintain financial and operational sustainability. Our latest analysis suggests that the outsourced CGT-manufacturing market will reach a value of US$57.1 billion by 2027, benefi...

Technology is a key driver in the deepening partnership between the United States and India. This collaboration has a longstanding history: The two countries have cooperated previously in critical areas such as disease control and surveillance, laboratory integration, and enhancement of public-health capacities ( 1 ). In recent years, that collaboration has intensified, especially in the field of biotechnology. Joint efforts now focus on using artificial intelligence (AI) for matching patients with treatments, applying nanotechnology for targeted drug delivery, and improving bioinformatic tools for comprehensive data analysis. Given the complexity of such initiatives, a collaborative approach will be crucial to accelerate outcomes in research, development, and drug discovery. The ongoing US–India connection could advance research significantly in those areas by fostering swift progress in biotechnology and healthcare, particularly in rapid drug discovery (RDD). The typical drug-discovery process is time-c...

Equipment cleaning is an integral and highly regulated part of pharmaceutical manufacturing for both large- and small-molecule drugs. Before equipment release, validation engineers perform visual inspections to verify the absence of visual residue. Such inspections include examination of small parts that are cleaned in a washer. In multiproduct biopharmaceutical facilities, product-agnostic methods such as swabbing for total organic carbon (TOC) content are used to assess product-carryover levels from one process to another ( 15 ). The TOC method’s limit of quantification (LoQ) is ~0.2 ppm. In BPI’s May 2024 issue, we began an evaluation into whether inspection based on visible residue limits (VRLs) is a viable, practical alternative for meeting cleaning requirements usually assessed by TOC. Part 1 focused on our experimental methods, materials, and calculations. We performed a small-scale VRL study that was designed to represent worst-case conditions for visual assessment in a biomanufacturing environmen...

Technicians can achieve contamination control during aseptic operations by applying two methods: gowning workers to minimize microorganism “shedding” and surrounding products with localized protection to minimize human contact. Gowning includes both disposable and relaundered suits (both circular and noncircular cleanroom textile solutions). Many organizations use relaundered suits for operator comfort. But the control of relaundered garments is a difficult compliance challenge, especially in relation to the number of times they can be reprocessed through laundry and associated controls. Whyte and Bailey established deterioration over time as a factor of garment reprocessing ( 1 ). Addressing such deterioration is crucial to facility contamination-control strategies. In the European Union (EU) good manufacturing practice (GMP) Annex 1, points 7.11 and 7.13 describe how cleanroom garment reuse should be subjected to formal studies for integrity and particulate control. For sterilised garments and eye cover...

Commercial-scale production of recombinant therapeutic proteins routinely involves suspension cultures of mammalian cells in bioreactors with up to 10,000 L capacity. With advances made over the past 30 years in cellular engineering, basal and feed media development, and bioprocess engineering, expression titers of ~10 g/L, viable-cell densities of >3 × 10 7 cells/mL, and specific productivities of >20 pg/cell/day are now common. Such high cell densities (with the potential to go even higher) increase mixing and aeration demands and can subject cells to aggressive environments such that they experience high hydrodynamic stresses. This installment of my bioreactor scale-up series should refresh your knowledge of fluid flow, mixing, and mass transfer in bioreactors, including how the interplay of those parameters creates the environment that cells experience. That in turn influences their growth, metabolism, and protein production. Fluid Flow in Bioreactors Fluids — either liquids or gases — are substances...

Advancements in modern engineered monoclonal antibody (mAb)–based therapeutics has led to a range of innovative and effective biomolecules and higher titers. However, the production process can result in high levels of aggregation and other product related impurities, posing downstream purification challenges.  Traditional chromatography methods for aggregate removal are limited in their operating range and effectiveness, often resulting in low recoveries or poor process economics. This article presents a design of experiments (DoE) study to investigate and optimize the performance of an innovative mix-mode chromatography resin used in flow through mode for the removal of high levels of aggregates in mAb feeds.   Monomer recovery and aggregate levels are presented for different chromatography conditions, as well as different loading densities.  Significant clearance of other process-related impurities such as hard-to-remove host cell proteins (HCPs) are also demonstrated. Read this article to discover how...