2012 ARTICLES.
The global pharmaceutical market is expected to reach $1 trillion by 2014 and nearly $1.1 trillion by 2015, according to the IMS Institute for Healthcare Informatics. With all of this growth in the biopharmaceutical market and recent concerns about pharmaceutical product shortages, companies and patients have been concerned about the availability of manufacturing capacity to produce these products. In BPTC’s recent analysis of global biopharmaceutical capacity, we find that overall capacity utilization rates have remained low despite the continued growth in sales of biopharmaceutical products and the associated requirement for increasing mammalian cell culture capacity to meet this market demand. To add to the capacity equation, there are many companies developing biosimilars, but the projected requirements for biosimilars currently in development is unlikely to significantly impact the global biopharmaceutical pipeline or the capacity demand for manufacturing within the next five years. While we forecast utilization rates to increase in the near-term future and understand the concern for a potential capacity shortage, we do not believe that an overall capacity shortage for biopharmaceutical manufacturing is imminent.
Commercialization of cell therapies will require the development of appropriate policies, procedures, and processes to address the large-scale GMP manufacturing, quality, and regulatory challenges of successfully bringing these new products to market. This article discusses the parallels between hurdles faced today in the manufacture of cell therapy products with those faced by the biotechnology industry in the early days of monoclonal antibody protein production. As with the manufacture of monoclonal antibodies, the establishment of platform processes for the manufacture of cell therapies and the adoption of single-use technologies for their production will enable companies to develop reliable, robust, and economically viable manufacturing processes for these products.
2011 ARTICLES.
Single use bioreactors for cell culture, single pass TFF systems for harvest, and disposable options for downstream processing have begun to see greater use in bioproduction. The significant advantages of single use technology in multi-product facilities such as contract manufacturing organizations and in enabling in-house production of early stage clinical material have enabled these technologies to gain a foothold in the bioproduction industry. In this article, the technology breakthroughs, regulatory concerns and solutions, and available types of single use bioreactors and downstream processing equipment will be reviewed.
How best to apply the concept of Quality by Design to biopharmaceutical products continues to be conundrum for biotech companies. A recent FDA-commissioned study by McKinsey & Co. finds that the industry is embracing QbD but FDA is struggling with internal confusion and disagreement over how QbD should be applied to biotech products and what type of data should be required to define a biotech design space. To facilitate broader acceptance and implementation of QbD, FDA must clarify exactly what data and how much they expect to support QbD-based submissions. Until such guidance is provided, companies will continue to struggle and QbD will not achieve its fullest potential.
2010 ARTICLES.
One of the greatest challenges facing biopharmaceutical companies is ensuring adequate manufacturing capacity for products that are under development and potentially years away from commercialization. Companies without existing manufacturing capacity must decide among several alternatives, including building internal manufacturing capability, acquiring existing manufacturing facilities, outsourcing production to a contract manufacturing organization (CMO), or combinations of these. We present the strategic and tactical implications of various "make versus buy" strategies and discuss such critical aspects of developing appropriate manufacturing strategies for biopharmaceutical products as capital investment and risk, CMO selection, and the timing and cost of building manufacturing capacity.
With combined 2009 revenues estimated to be over $40 billion, monoclonal antibody products have become the dominant component of the biopharmaceutical market. To aid companies in the development of monoclonal antibody products, BioProcess Technology Consultants recently published The Development of Therapeutic Monoclonal Antibody Products, a comprehensive report outlining the complex technical, regulatory, and strategic Chemistry, Manufacturing, and Control (CMC) activities necessary to successfully advance new monoclonal antibody products from discovery to First-in-Human clinical trials and the market as quickly and economically as possible. There are numerous interconnected tasks that must be completed in a timely and cost effective manner to enable human clinical testing of a new monoclonal antibody candidate. All technology developed prior to the first cGMP manufacturing run will need to be transferred to the manufacturing and product testing site(s). Later in product development, manufacturing processes and analytical methods are often transferred from the initial manufacturing site to facilities that can produce larger batches of product. Whether these transfers occur within a company or between different organizations such as from a company to a service provider, careful planning and management is essential to ensure the knowledge and experience gained during development and/or early clinical manufacturing is effectively transferred so that the receiving organization or party can perform the critical elements of transferred methods or process. The sending and receiving parties must be well aligned in expectations and plans. This is facilitated by early and detailed planning and communications. The better the process and product are understood in terms of CQAs and CPPs the greater the likelihood of a successful transfer and demonstration of comparability. Risks should be identified and controlled as best as possible. This article discusses each of these technology transfer considerations to enable a smooth and successful technology transfer process.
The current economic crisis combined with increasing competition and the need to make healthcare more affordable present formidable challenges to today’s biopharmaceutical industry. By 2015, spending on prescription medicines in the United States alone is forecast to be approximately $450 billion or greater than 10% of all US healthcare expenditures. Biologic products already account for almost 15% of the total market for pharmaceutical products. Spending on these products is expected to continue to grow in the coming years, with monoclonal antibody products being the fastest growing segment of biologic products.
BioProcess Technology Consultants recently published The Development of Therapeutic Monoclonal Antibody Products report which is an indispensable guide to the complex technical, regulatory, and strategic Chemistry, Manufacturing, and Control (CMC) activities necessary to successfully advance new monoclonal antibody products to clinical trials and the market as quickly and economically as possible. This article is a summary of Chapter 3, "Overview of CMC Activities for Monoclonal Antibody Development," which provides a synopsis of the key CMC development functions:
- Analytical Method Development
- Upstream Process Development
- Downstream Process Development
- Formulation Development
- Scale-up and Bulk Drug Substance Manufacturing
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Final Drug Product Manufacturing (Fill/Finish).
Sometimes drug development can feel like a Sisyphean challenge in the progress from laboratory bench to the clinic and, for a small percentage of companies, to the market. Global regulatory requirements, embodied in regulations governing Good Laboratory Practice (GLP), Good Clinical Practice (GCP) and Good Manufacturing Practice (GMP), collectively referred to as GxP, can intensify this frustration. These requirements exist, however, for very valid reasons, and when followed properly can actually decrease the risk and frustration that frequently goes hand-in-hand with drug development by providing a clear compliance roadmap.
2009 ARTICLES.
BioProcess Technology Consultants and PharmSource Information Services recently published a detailed report analyzing the complex and dynamic balance of supply and demand for mammalian cell culture manufacturing capacity for production of therapeutic recombinant proteins and monoclonal antibodies. This article summarizes the key findings and results from this report and provides commentary on several trends in biopharmaceutical manufacturing, including advances in technology which may lead to significantly lower utilization of existing capacity, globalization of the biopharmaceutical industry, and the emergence of biosimilar products.
In November 2008, the US FDA finally issued a new draft guidance on process validation. The new guidance is intended to reflect some goals of the FDA’s Pharmaceutical GMPs for the 21st Century, an initiative that was finalized in 2004. The new draft is to be applied to manufacturing human and veterinary drugs, biological and biotechnology products, finished products and APIs. Its key principle is alignment of process validation activities with the product development life-cycle and the use of quality by design (QbD).
