Manufacturing

eBook: mRNA — Negotiating New Manufacturing Hurdles

The emergency authorization, regulatory approval, and successful commercialization of Pfizer–BioNTech’s and Moderna’s respective mRNA vaccines for SARS-CoV-2 have ignited considerable interest in the modality across the biopharmaceutical industry — and for good reasons. Establishing a platform process for mRNA production could facilitate and accelerate several aspects of vaccine development and manufacturing. Drug makers also intend to leverage benefits associated with cell-free bioprocessing. But as the contributors to this eBook show, mRNA remains a nascent modality, and companies must surmount new…

Cell Therapy — Supply Chain Discussions

The 2017 approval of Kymriah (tisagenlecleucel) has paved the way for other cell therapy products to reach the patients who need them. Each passing year promises to open the regulatory floodgates to more product approvals, but technical and manufacturing issues continue to keep initially high expectations from being realized. One barrier is supply chain complexity, especially for the subset of autologous cell therapies. This eBook features expert commentary from Be The Match BioTherapies, a company providing more than 50 product…

Using Synthetic Biology To Develop Novel Biotherapeutics

A multidisciplinary area of research, synthetic biology involves the use of genetic engineering to create new biological parts, devices, and systems, with potential applications in industries such as healthcare, agriculture, energy, and environmental science. As early as the 1960s, researchers combined advanced techniques in precision genetic engineering with rational drug development and explored approaches in synthetic biology to support development of innovative drug products. Later research shed new light on how molecular networks regulate cellular function and how gene expression…

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…

Ensuring Single-use Systems Integrity in Aseptic or Closed-Process Applications

Due to their numerous benefits, single-use systems (SUS) have been increasingly implemented in biopharmaceutical processes in the past decades. Originally used in applications for the preparation and storage of buffer and media, SUS have become more and more important in the commercial production of biopharmaceuticals. Today, biopharmaceutical manufacturers use this technology in critical drug substance or drug product process steps such as formulation, bulk storage, bulk transport, and final filling of drug product. By using single-use technologies, manufacturers can reduce…

Allogeneic Cell Therapy Manufacturing: Preparing for Tomorrow’s Success

Cell therapies are promising new drug products that treat or cure diseases that, until the past decade, had no other treatment options. Several autologous cell therapies have been approved, and their efficacy has been proven, especially in immunooncology. However, autologous therapies can present some difficulties for both developers and patients (e.g., short timelines, point-of-care drug administration). Allogeneic cell therapies are not associated with those challenges. For example, patient access to an autologous treatment can take months, time that patients with…

eBook: Vaccines — From Disease Prevention to Treatment

For over two years, the biopharmaceutical industry has revolved around rapid development, manufacture, and rollout of vaccines in response to the COVID-19 pandemic. Now as the world reverts to some sense of normality, demand has plummeted for the likes of J&J’s viral vector vaccine and Moderna’s messenger RNA (mRNA) vaccine, resulting in the lowering of financial forecasts, ending of manufacturing contracts, and freeing of production capacity. But where do vaccines — the great pharmaceutical success story of the past few…

Addressing Unwanted Immunogenicity in Gene Therapies

Immunogenicity is the ability of a substance, such as a foreign and/or potentially dangerous protein, to provoke an antigen-specific immune response. However, some immune responses can be detrimental, such as in autoimmune diseases and unwanted reactions to biological therapeutics. The latter case can compromise biopharmaceutical safety and efficacy, and preexisting immunity against biologic components can preclude patients from receiving life-changing treatments, perhaps most notably in gene therapy (1). Gene therapies are designed to target the root cause of a genetic…

Building Manufacturing Capabilities for Adenoassociated Virus Vectors: Key Considerations for Facility Design and Operations

Demand for gene therapies based on adenoassociated virus (AAV) vectors continues to exceed manufacturing capacity. Part of the imbalance stems from the growing number of AAV-based candidates that are advancing through clinical studies. Zhao et al. report that, in September 2021, researchers were enrolling participants for and/or conducting 137 trials for such products (1). As of August 2022, three AAV-based therapies have received commercial authorization in the United States and/or European Union, and other products have received conditional approval (2–5).…

Statistical Method for Establishing Control Limits for Nonnormal Data Distribution: Focus on Continued Process Verification Monitoring

According to the US Food and Drug Administration’s (FDA’s) process validation guidance, critical quality attributes (CQAs) and critical process parameters (CPPs) are used to assess the statistical stability of a bioprocess and its ability to meet acceptable criteria as a part of a continued process verification (CPV) program using control charts (1). For those control charts, control limits are used to assess the statistical stability of process parameters and attributes. When data are normally distributed, control limits are established straightforwardly…