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The first article in this periodic series reviewed the impact of cost pressures on the biopharmaceutical industry, in particular the challenges the industry faces in relation to high capital costs, complex processes, and long product development cycles ( 1 ) . Here we examine what companies are doing to assess costs in decisions about process and technology choices relating to manufacturing of biologic drug substances. We will look into what companies are currently doing and what they need to be doing to control costs. Companies need to know from a strategic perspective how technology and process choices influence manufacturing costs within a portfolio of products; the type and timing of investments required to ensure sufficient manufacturing capacity; and how an understanding of costs can optimize risk management. Process development can be defined as the start of the product life cycle. At this stage a manufacturing process is defined in terms of unit operations (discrete manufacturing operations). Th...
One response to a survey we sent out last year kept coming back to me as we prepared this issue. In answer to what a company does if a product in development doesn’t fit into the company’s platform technology, one answer was, “We innovate a solution.” Whether meant seriously or not, it rings true to the history of the industry’s ability to invent and reinvent solutions as necessitated by economic realities. When we began working on the topic of this special issue, we thought we knew the trends and would simply be offering examples of the burgeoning of “local” manufacturing around the world. We assumed that the global biotech industry had reached a sort of geographical “tipping point,” when in actuality, the choices appear to be much less clear-cut. It is true that what has in the past been accomplished by vertically integrated companies in major biotech hubs can now be done pretty much anywhere in the world. This presents companies, new and established, with a number of business models and options — but n...
Pharmaceutical companies of all sizes outsource at least some quality control (QC) testing to contract analytical testing laboratories. Virtual and smaller companies may not have the staff to conduct such testing, whereas mid- to large-size companies may outsource testing that they do not wish to perform in-house. In the relationship between a pharmaceutical company and its outsourcing partner, each partner has clearly delineated responsibilities, both business and compliance related. In May 2010, we discussed a contractee’s (contract giver’s) responsibilities ( 1 ). Here, we focus on those of the contractor (contract acceptor), limiting our attention to responsibilities in the contractee– contractor relationship. Neither discussion addresses purely business-related concerns such as revenue growth, development and retention of staff, and shareholder reward. Compliance The laboratory to which a pharmaceutical company outsources QC testing in effect becomes an extension of that company’s own QC organization...
Vaccine makers are leading the way — that’s something you don’t hear every day. For many years, vaccines were seen as “old-school” and less profitable than other biologic products — and they were the business of just a few huge companies. But thanks to recombinant technology, it’s a real Cinderella story: Advancing technologies led to what’s being called the “vaccine renaissance.” And now, vaccine companies may have something to teach their biopharmaceutical brethren. In April 2004, BPI may seem to have been speaking too soon with its “Vaccine World” supplement, in which I wrote of cell-culture–based vaccine manufacturing as though it were a done deal ( 1 ). It made perfect sense to me (as a technically inclined but not economically inclined sort of person), especially for the new vaccine products that were being developed ( 2 ). In the same special issue, two former BPI editors pointed to another aspect of the vaccine business that was driving it in new technical directions: the conflicting economics of ...
It is generally accepted that quality cannot be tested or inspected into a finished product, but rather that quality, safety, and effectiveness must be “designed” and built into a product and its manufacturing process. To encourage new initiatives and provide guidance to pharmaceutical process developers, the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use introduced the quality by design (QbD) concept. ICH-Q8 defines it as “a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management” ( 1 ). A typical bioprocess for manufacturing an active pharmaceutical ingredient (API) is influenced by a complicated matrix of input and output parameters, including critical process parameters (CPPs) critical quality attributes (CQAs), as illustrated in Figure 1. Those input parameters may be interlinked or independent...
As the biopharmaceutical industry undergoes restructuring, its focus shifts to the efficiency of drug development and overall costs of delivering affordable medicines. A question often raised concerns the manufacture of drug substances overseas to tap into a cheaper manufacturing base ( 1 ). There are many issues to consider when looking at overseas locations, such as intellectual property (IP), the availability of skilled labor, and the emergence of new markets. The situation is more complex with biopharmaceuticals because the products themselves are difficult to characterize, which means close scrutiny of all systems manufacturing, quality, and supply chain. However there are successful overseas manufacturing companies supplying vaccines through World Health Organization (WHO) programs, and blood fractionation facilities and established biopharmaceutical manufacturing operations are already operating in Cuba, China, Japan, Singapore, and India. I’m focusing on the economic aspects of biopharmaceutical m...
For a growing number of biopharmaceutical companies, the world is getting smaller. They are operating in smaller, more flexible facilities; servicing potentially smaller markets; and managing local products. Local manufacturers are looking for ways of doing standard processing less expensively without making changes that carry regulatory risk. Most of these facilities are vaccine manufacturing sites. The upsurge in localized diseases and need for global pandemic preparedness (especially under uncertain capacities) have countries such as Malaysia, India, China, and Brazil pushing for local production plants to supply vaccines and other drugs. Legislative and social changes such as US healthcare reform, worldwide recessions, and the push for increasing biosimilars are driving the need for greater manufacturing efficiency. To become more efficient in processing, localized manufacturers will need to become aware of the impact of social, legislative, and technology factors that are fueling this trend toward de...
Cell therapy using embryonic or adult stem cells for regenerative medicine is generating high interest in the global medical community and in the general population.Physicians and patients are looking to cell therapies as potentially curative treatments for diseases such as diabetes, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, Graft versus Host disease (GvHD), and cancer. Cell-based therapeutic products have been administered in clinics for nearly 90 years in the form of blood transfusions and for 50 years in the form of bone marrow transplants. With vast improvements over the past two decades in cell characterization, isolation, and in vitro manipulation, cell therapy has grown to include FDA-approved products such as PRODUCT FOCUS:CELL THERAPIES PROCESS FOCUS:MANUFACTURING WHO SHOULD READ: R&D, PROCESS DEVELOPMENT, QA/QC, MANUFACTURING KEYWORDS: CELL ISOLATION, CELL PROCESSING, CLINICAL TRIALS, FACS (fluorescence-activated cell sorting), flow cytometery, CGMP LEVEL:INTERMEDIATE Cell therap...
Compared with other business sectors, the biopharmaceutical industry has been a high-tech laggard when it comes to outsourcing and off-shoring. That’s changing as companies acknowledge the strategic, cost, and market benefits. Over the past seven years of tracking outsourcing trends ( 1 ), I’ve seen interest in outsourcing grow, but that has kicked into high gear over the past couple years. Partly due to the economic and funding crisis and partly as a result of industry maturation, outsourcing is taking greater prominence as biopharmaceutical companies gain experience in managing outside operations. Bioexecutives are considering outsourcing models and creating the tools needed to assess different operating strategies. This year, our seventh annual survey of biopharmaceutical manufacturing and capacity analyzed the data of 327 global biomanufacturer respondents and 125 suppliers to this industry. As detailed in the “Survey Methodology” box, the results cover a broad range of issues including capacity and o...
Development of cell and tissue therapies presents bottlenecks in manufacturing process development and scale-up as commercial and academic groups move from small-scale research and development (R&D) to more complex logistics. Often, the simplicity of maintaining cell yield, viability, and function in a laboratory setting cannot be replicated when source tissue and final therapeutic products are subjected to the extended distances and times of actual clinical delivery. These bottleneck issues have a number of causes. One specific and common cause is suboptimal biopreservation workflow processes and practices. At BioLife Solutions, we often address this particular issue in consultations with current and prospective customers, where we’ve heard the title of this article from a number of people. The following case study — a hypothetical amalgam drawn from our experiences — highlights various biopreservation workflow process optimization steps that can extend stability. This may improve postpreservation viabil...
Bioreactor Scale-Up Product: Micro-24 MicroReactor system Applications: Early stage microbial process development Features: With Pall Corporation’s acquisition of California-based MicroReactor Technologies, Inc. in January 2010, Pall Life Sciences offers the Micro-24 system. It features a disposable 24-reactor cassette, each reactor with fully independent control of temperature, pH, and dissolved oxygen. The miniature bioreactors enable rapid, high-throughput process development with accurately scalable results. The systems simulate the performance of stirred-tank bioreactors from bench (1–20 L) up to 200,000 L. Contact Pall Life Sciences www.pall.com/bioreactors Development Services Service: Vetter Development Service Features: At its new Chicago, IL, facility Vetter offers manufacturing services from preclinical development through phase 2, with scale-up and transfer to its commercial manufacturing facilities. Services include primary and secondary package development, process development, clinical...
The idea of “thinking globally, but manufacturing locally” to each market is relatively new to the biopharmaceutical industry. As I mentioned in Chapter 2, vaccine makers are more familiar with the concept already. But many technological and economic factors are making other companies aware of this option. Offshoring clinical trials has been of great interest in the pharmaceutical industry for years now. Is it more cost-effective to make clinical materials “here” and ship them “there”— or to make them where they’ll be used? Can you maintain proper control over product and process, not to mention intellectual property and regulatory compliance? As with any other business strategy, these are not ventures to be taken lightly. There are pitfalls to avoid and rough waters to navigate along the way — and this kind of globalization may not be the way to go for some. For others, however, it could provide solutions to some very daunting challenges standing in the way of their success. Recently Novozymes Biopharma’...
IBC’s BioProcess International conference and Exhibition has become the largest, most well-respected forum that focuses solely on technical, regulatory, and strategic planning challenges in the manufacture of biotherapeutics. This event is truly the place to gain the latest industry updates, make new contacts and initiate collaborations in biopharmaceutical production. Why? Four comprehensive tracks will update your knowledge in all areas of bioprocessing at one outstanding forum Managing Manufacturing Networks: Maximize your present and future facilities from experience with biodefense, subcutaneous high dosing, high-titer projects, and many other cutting-edge case studies and strategies. Product Lifecycle Management: Learn to use design space strategy to leverage flexibility, mitigate variability, and continuously improve your process. Cell Culture and Upstream Processing: Hear what comes next after titers increase as companies demonstrate approaches to accelerate process development and control co...
Business or research groups planning to expand research, manufacturing, sales, or distribution activities beyond the United States should plan for compliance with US and international export and import rules and understand how these rules apply to various technologies. Export and import requirements can be complex and highly technical. Failure to allow for the long lead times needed to frame and implement internal export policies and procedures as well as engage third-party export services can lead to additional expenses, delayed export schedules, financial penalties, and criminal charges. Recent aggressive enforcement of US export laws have resulted in civil penalties amounting to >$100,000 against several companies engaging in unlicensed exports and re-exports. Initial Considerations Specialists must plow through lengthy and complex commercial export rules and packing, labeling, and shipping requirements. A general understanding of such rules in the United States (as well as related costs) is essential ...
Single-use technology began on the downstream side of bioprocessing, primarily in presterilized filter capsules and plastic biocontainers for buffers and media. Since then, it has expanded to upstream operations, including disposable bioreactors and mixers. The newest trend is to move further downstream into sterile formulation and filling. With the increasing popularity of disposable systems, some users are wondering what is being done to standardize the various components from different manufacturers and what BPSA (the Bio-Process Systems Alliance) is doing to address these and other industry concerns. Jerold Martin, senior vice-president of global scientific affairs at Pall Life Sciences and Chairman of the Board and Technology Committee for BPSA, discussed these topics with BioProcess International. Standardization BPI: Standardization is a major concern with single-use technologies; what are the main schools of thought about this? JM: Standardization is an interesting concept. Some people are aski...
With combined 2009 revenues estimated to be over US$40 billion, monoclonal antibody (MAb) products have become the dominant component of the biopharmaceutical market ( 1 ). Continued interest and development of this exciting class of products will drive the overall sales of biopharmaceutical products in the future, making them the fastest growing segment of the overall pharmaceutical market ( 2 ). To help companies developing MAb products, BioProcess Technology Consultants recently published a comprehensive report outlining the complex technical, regulatory, and strategic chemistry, manufacturing, and control (CMC) activities necessary to successfully advance new MAbs from discovery to first-in-human clinical trials and the market as quickly and economically as possible ( 3 ). As discussed in the report, numerous interconnected tasks must be completed cost effectively and on schedule to enable human clinical testing of a new MAb candidate. Those tasks include construction and testing of production cell li...