Manufacturing

eBook: Drug-Delivery Systems — Measurement-System Analysis Using Gauge R&R Studies

When a biological product requires a specialized delivery device, the resulting combination product can introduce new types of quality evaluation. Product development brings together regulatory requirements for biologics and drug-delivery systems, and for many people on the biopharmaceutical side, that includes a number of unfamiliar terms, processes, and procedures. Among those are gauge repeatability and reproducibility studies for measuring variations that arise from measurement devices and the operators using them. This eBook introduces the concept of attribute-data gauge repeatability and…

Hardware, Software, and Wetware: 20 Years of Advancements in Biopharmaceutical Production, Part 2

The past couple of decades have witnessed significant advances in upstream bioprocess technologies and approaches. Since its establishment, BPI has been a facilitator of discussion both in print and at professional conferences, as well as in webcasts and news online. To mark the 20th anniversary of the publication, we surveyed articles published over the past two decades and found hundreds that highlight significant advances in both emerging and established themes in biopharmaceutical production: • “hardware” technology (e.g., analytical instrumentation, bioreactors,…

Future Supply-Chain Needs for Allogeneic Cell Therapies: Why Strategic Partnerships Are Critical

Allogeneic products are an attractive option for cell-therapy developers because multiple batches can be manufactured using apheresis material collected from one healthy donor — and because the resulting therapies could be made available as off-the-shelf products. The appeal of this approach is apparent from growth in allogeneic-therapy development. According to the Alliance for Regenerative Medicine, the number of clinical trials for allogeneic cell-based cancer treatments has increased by 30% over the past five years. Early in 2022, allogeneic candidates accounted…

Synthetic Biology for Adapting CHO Cells to Challenging Bioprocesses

Biopharmaceuticals are produced mainly by Chinese hamster ovary (CHO) cell lines, for which advances in protein formats, bioprocesses, and bioprocess control are introducing novel challenges (1). Thus far, those challenges have been tackled either by technical innovations and media optimization or by advances in host-cell engineering (2, 3). Some technical innovations bring further challenges, such as those related to the compatibility of CHO cultures with highly automated bioprocesses and continuous high-density culture modes (4). With regard to host-cell engineering, most…

Raman Spectrometric PAT Models: Successful Transfer from Minibioreactors to Larger-Scale, Stirred-Tank Bioreactors

Spectroscopic sensors are powerful tools for bioprocess monitoring within the process analytical technology (PAT) initiative of the US Food and Drug Administration (FDA). The PAT framework includes process understanding based on scientific background with the aim of monitoring and controlling critical process parameters (CPPs) that influence critical quality attributes (CQAs) of final biological products. The driving force for PAT implementation is a need to realize consistent product quality, process intensification, and real-time manufacturing control (1, 2). Using real-time spectroscopic measurements…

Deriving Mesenchymal Stromal Cells from Umbilical Cord Lining and Wharton’s Jelly: A Comparative Study of Extraction Methods and Culture Media

Mesenchymal stromal cells (MSCs) are multipotent, self-renewing progenitor cells that can differentiate into adipocytes, chondrocytes, and osteocytes (1). Cultured MSCs are plastic-adherent and spindle-shaped, and they express cell-surface markers CD44, CD73, CD90, and CD105, but not CD14, CD34, CD45, CD11b, CD79a, CD19, or HLA-DR (2, 3). First isolated from bone marrow (BM), human MSCs have been investigated extensively in clinical studies. MSCs also have been isolated from adipose tissue (4) and peripheral blood (5). Perinatal organs and tissues such as…

A Plug-and-Produce GMP Plant for Cell and Gene Therapy — Part 1: Case Study in Modular Facility Design and Deployment

The use of approved advanced therapy medicinal products (ATMPs) remains limited despite their potential to address unmet medical needs. One example uses chimeric antigen receptor (CAR) T cells for treatment of refractory lymphoma (1). Typically, such medicinal products begin with cells that are harvested from a patient and genetically programmed to recognize and eliminate tumor cells upon reinfusion. Several cell therapies based on this and other technologies are approved for use in the United States, Europe, and China (2). Given…

Overcoming Challenges in Viral Vector Production for Gene Therapy Using HEK Cell Cultures

An estimated 300 million people worldwide live with rare diseases, and over 70% of such disorders are caused by genetic mutations (1, 2). Cell and gene therapies offer hope and potential cures for many previously untreatable diseases. Accordingly, the global gene therapy market is expected to be worth USD 5.02 billion by 2028, a significant growth from USD 1.46 billion in 2020 (3). Manufacturing gene therapies will be a key challenge over the next two decades. But just a few…

Leveraging Prior Knowledge to Demonstrate Analytical Competency

Analytical groups are developing more methods than ever to address mounting demand for biopharmaceuticals. Still, such teams need to work within tight timelines to help candidate therapies advance quickly through clinical trials. During a May 2022 presentation, Rajgopal Rudrarapu (senior scientist at the Almac Group) pointed out that regulatory agencies allow biomanufacturers to apply prior knowledge to facilitate analytical development and validation. He described how his company leveraged prior knowledge to develop and validate a capillary isoelectric focusing (cIEF) method…

Bringing Gene-Therapy Product Quality Into Focus

Regulatory agencies are scrutinizing gene-therapy product quality more closely than ever, yet such therapies still are produced in small batches and at high costs. Thus, drug companies are struggling to make safe and efficacious gene therapies available to patients. In an April 2022 presentation, Tim Kelly (chief executive officer of Oxford Biomedica Solutions, OXB Solutions) emphasized the importance of addressing both process output and product quality when manufacturing adenoassociated virus (AAV)-based gene therapies. Such an approach requires deep expertise and…