Polymers provide a unique set of material properties, including toughness, chemical resistance, versatility, and low cost for both multiple-use and single-use bioprocessing systems. Polymer materials are manufactured as fittings and tubing for research and development (R&D) laboratories, as containers for bulk chemical and biological storage, as filters and separation technologies for downstream processing, and as containers and bottles for drug substance storage. These components and systems are helping drug companies improve their manufacturing flexibility, reduce their operating costs and capital spending, and shorten their drugs’ targeted time to reach clinical trials.
Along with the benefits of polymer materials come concerns about how extractables and leachables could influence manufacturing processes — and ultimately pharmaceutical product safety, efficacy, and/or stability (
1
). Industry organizations such as the American Society of Mechanical Engineers (ASME) and its bioprocess equipment (BPE) c...
+1It has been 10 years since the US Food and Drug Administration (FDA) articulated — in its guidance for process analytical technology (PAT) — the goal of “facilitating continuous processing to improve efficiency and manage variability” (
1
). Since that time, regulators and industry have worked toward applying continuous processing (CP) to all facets of pharmaceutical manufacturing, including bioproduction (
2
,
3
). Last year, the European Medicines Agency (EMA) referred to CP in its draft
Guideline on Process Validation
, and the FDA released a strategic plan,
Advancing Regulatory Science
, which includes an advocacy of CP (
4
,
5
). In 2012, Genzyme (a subsidiary of Sanofi), a major player in the single-use systems (SUS) arena, reported on the development of an integrated continuous bioprocessing approach as a potential universal platform for manufacturing protein biologicals (
6
). And just this year, Amgen and GlaxoSmithKline announced significant commitments to CP in an effort to improve efficien...
To enable broad, global access to life-saving biopharmaceutical products, our industry is facing significant pressure to reduce the overall cost of manufacturing and enable local manufacturing where possible. Combined with growing markets outside the United States and Europe and development of high-titer, high-yield processes, that pressure has led to a shift in the industry’s approach to facility design and construction. Today’s biopharmaceutical production facilities must be flexible, cost effective, and readily constructed with minimal capital investment and construction timelines. As available single-use products for biopharmaceutical manufacturing have advanced and modular facility design and construction have improved, the industry has developed modular, flexible biomanufacturing facilities that can be easily replicated in multiple locations.
We discussed advantages of combining single-use technologies with modular construction in the first of this three-part series (
1
). Here we present an economi...
+5 The multibillion-dollar global biopharmaceutical industry is placing increased emphasis on development and manufacture of advanced biologics. Such products offer exciting potential for the development of drugs that could provide as-yet-unknown treatments for a wide array of diseases.
One important goal is to commercialize biologic products as early as possible within the typical 20-year patent window. Patent submission must occur during drug development. Much work follows a patent filing, including further product development, toxicity checks, and clinical trials. Hopefully, US Food and Drug Administration (FDA) approval also occurs during this period. Following approval, developers need to take all necessary steps to properly make their products at commercial scale and execute market introduction plans. If a drug’s development takes much time after approval, the patent may run through a good portion of its window of protection before that product has a chance for commercialization. In some cases, only ab...
Tissue engineering is a multidisciplinary science that applies principles from engineering to the biological sciences to create replacement tissues from their cellular components (
1
). Resulting neotissues can repair or replace native tissues that are diseased, damaged, or congenitally absent. One technique that has come into widespread use is based on seeding cells onto a three-dimensional (3D) biodegradable scaffold that functions as a cell-delivery vehicle (
2
). Cells attach to the scaffold, which then provides space for neotissue formation and can serve as a template for directing neotissue development. As a scaffold degrades, new tissue forms — ultimately creating a purely biological substrate without any synthetic components.
Cells seeded onto a scaffold can be harvested from one patient who requires a tissue-engineered construct, thus eliminating the risk of immune rejection. The resulting fully autologous neotissue is perfectly biocompatible and can become completely integrated into the host. Ne...
+1 Sampling is used extensively to monitor both behavior and quality throughout biopharmaceutical processesing (
1
,
2
). Methods must deliver representative samples and — more important — not compromise the integrity of a given unit operation or the process of which it is part. When microorganisms, animal cells, viruses, or nonfilterable materials are involved, sampling methods must not introduce contamination (see the “Regulatory Requirements” box). For successful sampling, three methods have been used routinely over the years: steam-in-place (SIP) valves; aseptic tube welding; and single-use, presterilized sampling devices.
Each method has its advantages and limitations. When a source of steam cannot or should not be brought to a small and mobile stainless steel vessel, a commonly used method is full autoclaving, in which the entire vessel is placed in a large autoclave for sterilization. Tube welding by heat is a method that remains in use and could be considered for a fully autoclaved vessel; however, ...
During the past decade, single-use bioreactors have become widely accepted for use in cell culture process development and clinical manufacturing. Their key benefits over stainless steel bioreactors are flexibility, cost, and time savings associated with the reduction of cross-contamination risks (
1
). Here, we describe our approach to development and qualification of the Biostat STR single-use, stirred-tank bioreactor. Unlike other stirred single-use bioreactors, it offers a similar design to that of well-established, conventional (stainless steel) stirred-tank bioreactors. Disposability of the single-use cultivation chamber gives it robustness, reliability, and reproducibility of biological results together with a supply assurance needed to meet biopharmaceutical industry requirements.
Development
of a single-use bioreactor involves different phases of work (Figure 1). The starting point should be a clear definition of the product’s intended application. Typically, related requirements are captured in...
+6 When the editors of BPI asked us at BPSA to put together a content-rich article for the single-use supplement, we were happy to do so. Our challenge was how to bring in multiple viewpoints about the growing business of single-use that would be a “quick read” for the BPI audience. The answer: an expert colloquy (a “conversational exchange or topical dialogue”). Represented here are several of the most qualified industry spokespersons in single-use — all are members of BPSA and speak as directors of the alliance. Their message: Single-use adoption is growing. BPSA has enabled significant educational initiatives responding to many technical concerns with plastic-based systems. And there is still much to be done as the end users of single-use systems begin to assay how to implement these innovative, flexible manufacturing platforms for drug and vaccine production. It’s been said that the transition between old and new is never elegant or seamless. But in the case of single-use, BPSA serves to smooth that tran...
+1 Plastic-based, single-use, disposables has been prevalent in biotech/pharmaceutical manufacturing processes for decades. Examples of such technologies include filters, gaskets, tubing, sampling bags, carboys, and ultrafiltration/diafiltration (UF/DF) capsules. In recent years, single-use technology has made great leaps in broadening the range of options and applications available. Disposable bioprocess containers are now widely used for applications such as media/buffer preparation and storage, bioreactors and cell culture operations, in-process intermediate containers for manufacturing operations, final drug substance/product containers, and so on. Customized solutions are now readily available to the industry in the form of bioprocess containers with custom filters, tubing, fittings, and sampling assemblies.
Because disposables are typically presterilized with gamma irradiation, they pose distinct, well-documented advantages over traditional stainless steel equipment. Some such advantages include reduce...
