Most people in the biopharmaceutical industry recognize, at least anecdotally, that the use of disposables in biomanufacturing is moving forward. At BioPlan Associates, we’ve tried to quantify how things are advancing and capture some of the shifts in attitudes, especially in light of current economic challenges. The major shift is that decisions are being made more from an operational point of view. It’s become less a question of
if
disposables will be implemented than of
where
and
how.
Our newest industry study shows that concerns over adoption are rapidly becoming less strategic and more operational and commercial (
1
). As the “Methodology” box explains, this year’s study elicited data on 10 critical areas associated with biopharmaceutical production (disposables being one of these) from 443 production executives at drug developers and CMOs in 39 countries.
This year, decision makers’ objections to disposables have declined both in quantity and importance. For example, we asked respondents about...
Disposable technology for bioprocessing is efficient and cost effective in many product development scenarios. For an industry dedicated to improving human health, however, the environmental contributions of a product must also influence its bottom line. Product transitions evaluated within a people/planet/profit framework require assessment regarding shifts in human and environmental impact. Life-cycle assessment (LCA) offers one perspective by evaluating the environmental loading of inputs and outputs to a product or process. The contribution of individual product life-cycle stages to a total environmental load can be used to inform design of next-generation disposable products and optimize process development when a clear economic preference is not apparent.
Framework:
Disposables are a flexible alternative to conventional bioprocessing equipment for unit operations in which rapid development, space constraints, overhead costs, or maintenance capacity limit the applicability of stainless steel systems...
Establishment of standard production platforms can help vaccine development move a step closer to the commercial, technical, and regulatory benefits increasingly enjoyed by developers of monoclonal antibody (MAb) products. Three recent advances especially will assist vaccine manufacturing development: rapid analytical methods to support evaluation of process design and provide in-process control; and the establishment of supply chains and vendors across Asia for bioprocessing equipment and consumables that meet the highest international standards. Whereas some workers in the field may consider the goal of achieving mass vaccination through a standard production platform impractical, there will be tremendous benefits if the technical and commercial problems can be resolved.
Manufacturing Design and Development Challenges
MAbs are now firmly established as a mainstream class of biopharmaceuticals with a reasonably generic platform manufacturing design (
1
,
2
,
3
). There is an expanding range of contract m...
+1Many biotechnology companies recognize the powerful benefits of increasing product titer early in product development as a strategy to minimize manufacturing costs, scale, and the duration necessary to produce clinical supplies and achieve product commercialization. Additional benefits include minimizing or completely avoiding significant regulatory delays to market that can be caused by major process technology changes (such as cell line and product quality changes).
Recently, another significant benefit has been realized too: Smaller, more productive and efficient 2,000-L single-use bioreactors and purification systems can meet market demands if enough improvement is achieved in manufacturing productivity early on. These systems eliminate the enormous expense, duration, and risk of building large-scale stainless steel manufacturing plants.
Improvements achieved in scaled-down robotic high-throughput screening technologies can at best simulate large-scale performance but not guarantee it. However, succes...
+7 Mycoplasmas and related bacteria in the class
Mollicutes
are parasitic organisms found not only on the external surfaces of a wide range of eukaryotic host cells, but also intracellularly. They are characterized by small size and lack of a rigid cell wall, which gives them resistance to β-lactam antibiotics and the ability to pass through 0.2-µm filters (
1
,
2
). Contamination by
Mollicutes
is a common problem for cell cultures that is not easily detected because it usually does not produce turbidity or cytopathic effects even though high densities are achievable (10
5
–10
8
organisms/mL) (
3
). A contaminated product-producing cell culture may not be apparent, but the contamination can affect cell growth and alter the metabolic and biochemical characteristics of contaminated cells — and it may lead to unsafe final products (
2
).
PRODUCT FOCUS:
ALL BIOLOGICS
PROCESS FOCUS:
PRODUCTION
WHO SHOULD READ: QA/QC,
PROCESS DEVELOPMENT, PRODUCT DEVELOPMENT, AND ANALYTICAL PERSONNEL
KEYWORDS:
LYOPHILIZA...
+9 During the past few years, use of disposable bioreactors in development and manufacturing processes has become widely accepted. Particularly, low–oxygen-demanding cell types such as human and insect cells have proven to be perfectly suitable for cultivation in single-use bag chambers. These bioreactors have significant advantages over their reusable counterparts (
1
). They transform a single-purpose process using stainless steel reactors into a multipurpose facility in which switching from one application to another is both easy and cost effective.
Reusable stainless steel bioreactors have fixed vessel configurations with predefined port assemblies, whereas single-use bioreactors use presterilized plastic cultivation chambers that get discarded after use. That makes adapting such cultivation vessels to specific applications highly convenient. Because single-use bags are presterilized by their suppliers, sterilization/cleaning is not required. That eliminates space-consuming and expensive clean-in-place (...
+3 Osmolality and pH are important cell culture process parameters, key elements that are often examined and optimized to improve the productivity of cell-culture–based bioprocesses. Osmolality affects cell viability and growth by regulating the transport of water and nutrients through cell membranes and pH maintains the isotonicity of a culture. To monitor these parameters in cell culture, samples are typically withdrawn and passed through a multifunction analyzer as the BioProfile 400 instrument from NOVA Biomedical (
www.novabiomedical.com
). Withdrawing samples during a bioreactor operation can introduce contamination and lead to sepsis.
Osmolality is often determined using an off-line osmometer, and pH by potentiometric-based electrodes. Although in situ pH measurement is possible, it has some inherent technical challenges such as buffer precipitation and glass membrane cell clogging that reduce test result quality. Near-infrared spectroscopy (NIRS) offers an in situ, real-time monitoring capacity for b...
+5 S
ingle-use technologies are becoming more widely accepted by biopharmaceutical manufacturers than ever before. The market is complex, fast-growing, and dynamic, which means integrated innovative technologies are the key to keeping pace with biopharmaceutical manufacturing needs. In fact, end users are already beginning to move away from singular disposable components to increasingly require suppliers to provide integrated solutions for specific process needs. So it is critical for suppliers to work closely with their customers and provide novel solutions.
Why the Switch?
Biopharmaceutical manufacturers are confronting the challenge of commercializing their new biological drugs faster and at lower cost than before. To meet those goals, many strive to develop more efficient processes. Single-use technologies present a sound solution.
Switching over to single-use technologies doesn’t require the “hard sell” that it used to because the benefits of such technologies have become evident. According to BioPlan A...
Laboratory scientists often assume that their liquid-handling instruments, from pipettes to automated liquid handlers, are operating within specification. But given that data integrity for applications from drug discovery to molecular diagnostics relies on accurate and precise liquid delivery, that can be a very risky assumption with high costs of failure. Those costs and risks are compounded by several trends in today’s life-science laboratories, such as the growing use of valuable reagents at low volumes and an increasingly strict regulatory environment. Because the need for quality assurance is more critical than ever, laboratories require the most accurate, precise, and convenient methodology possible to verify the performance of their liquid handling instrumentation.
PRODUCT FOCUS: ALL BIOLOGICS
PROCESS FOCUS: R&D, ANALYTICAL
WHO SHOULD Read: QA/QC, R&D, AND PROCESS DEVELOPMENT
KEYWORDS: CALIBRATION, BIOASSAYS, LIQUID HANDLING, VALIDATION, CELL-LINE DEVELOPMENT, DRUG DISCOVERY
LEVEL: BASIC
In providi...
Cryopreservation
Product:
CryoSolve single-use CGMP cell cryopreservation media
Application:
Cell cryopreservation
Features:
These single-use syringes with Luer-lock tips help eliminate sharps, avoid cross contamination, maintain sterility, and streamline your process. Raw materials are serum-free (USP/EP) and the medium has been shown to support an average cell viability of 97%. The products are manufactured under CGMP conditions with syringes made of USP Class VI glass, compatible with DMSO. All equipment passed compatibility studies and meets the requirements of low leachables/extractables, low toxicity, and high purity.
Contact Akron Biotech
www.akronbiotech.com
Optical Sensing
Product:
Visiferm DO
Application:
Cell culture and fermentation
Features:
The Visiferm DO is an optical dissolved oxygen sensor that reduces measurement time and is easier to use than classical technology. Symmetrical, heat-resistant, dual-channel optics and measurement amplifier are self-contained in a standard 12-mm f...
The fourth annual BioProcess International Analytical and Quality Summit offers a focused look at solutions and approaches to problems facing analytical scientists in product characterization, assay development, method validation and quality control. Separate conference tracks are dedicated to biophysical analysis, posttranslational modifications, and method validation — with an additional track to tie those fields to the need for improved product understanding associated with quality by design. This multitrack format allows you to customize your conference experience based on your personal job function and responsibilities and the needs of your organization.
New for 2009
Preconference Workshops:
“Early Phase Characterization of Your Molecule” and “Planning and Risk Assessment for Analytical Qualification and Validation”
Conference Sessions:
Analytical and Quality Leadership Keynote Forum … High Throughput Biophysical Analysis … Critical Quality Attributes Related to Posttranslational Modifications … Va...
Many different rapid microbiological methods (RMM) have been developed in recent years, although their acceptance and implementation in the pharmaceutical industry has been slow. To stimulate the integration of RMMs in the pharmaceutical industry, the Food and Drug Administration (FDA) introduced the Process Analytical Technology (PAT) initiative in 2004. A year later, the
Encyclopedia of Rapid Microbiological Methods,
edited by Michael J. Miller, was published. Miller, senior research fellow in the manufacturing and science department at Eli Lily, recruited many authors, mainly from highly recognized institutions in the United States, to contribute to the work.
The encyclopedia comprises three volumes, each with 17 to 18 chapters. Each chapter ends with short biographies of the authors. In the first volume, themes such as the history of microbiology, validation strategies, PAT, and the PDA Technical Report No. 33 are covered. Volumes two and three deal with different RMMs and include instrumentation an...
