Validation Articles

Strategies for accurate speciation and case studies for the detection of cell line cross-contamination using a commercial kit. Confirmation of purity and identity of cell cultures is a necessary step in the production of biotherapeutics. Manipulation of multiple cell lines in the same facility introduces the possibility that cross-contamination may occur. Different cell lines may proliferate with varying growth rates such that a single cell from a rapidly growing line, introduced into a culture of slower growing cells, can overtake the original culture in the course of a few passages. In addition, cultures may be mislabeled during manipulation, again resulting in a misidentification of the culture. The need to verify the purity of cell lines on an ongoing basis is critical.

Common issues addressed by life sciences regulations include control and record accuracy. As the bustle of Sarbanes-Oxley (SOX) 2004 compliance deadlines for companies winds down, executives have an opportunity to reconsider their company's compliance strategy. In 2005, AMR Research predicts SOX compliance costs will exceed $15 billion.1 The CPA Journal estimates that first year Section 404 compliance costs for companies with a net worth over $5 billion will exceed $4.6 billion, and small to medium companies on average of $2 million.2 Some are questioning the value of complying with SOX and its associated costs.

Purifying MAbs with novel supports works as well as Protein A. The introduction of new protein-based therapeutics such as monoclonal antibodies (MAbs), MAb-based vaccines, growth factors and plasma proteins implies the need to study, characterize, and purify. The separation step is likely to be a bottleneck and cost-effective technology will be needed to rectify it. The currently prevalent matrices for chromatographic separation of immunoglobulins (Igs) are based on Protein A or its recombinant versions (Protein G).

Monoclonal antibodies (MAbs) represent the fastest growing pharmaceutical market segment. Even with conservative assumptions about growing attrition rates, substitution pressure, and margin squeezes, MAb sales will probably reach a stable plateau of $20 billion by 2010. While the commercialization of MAbs is gathering momentum, the sector is facing a worldwide shortfall of available biomanufacturing capacity that is becoming a critical strategic limitation, especially for companies without established market access. Improvements are due in all areas of the pharmaceutical supply chain but especially in downstream processing to manage current manufacturing challenges and are therefore vital for the long-term success of the sector.

Twelve biopharmaceuticals gained marketing approval in the US and EU in 2004. Antibody-based products represented the single largest product category.Currently, some 160 biopharmaceuticals (defined as recombinant therapeutic proteins, monoclonal antibody-based products used for therapeutic or in vivo diagnostic purposes, as well as nucleic acid-based products) have gained marketing approval in the US and EU. Approx-imately one-fourth of new drugs coming on the market are biopharmaceuticals.

Life sciences businesses are turning to outsourcing as a way to drive down costs and support critical process quality. Your company's job is to make biopharmaceutical products. Managing facilities is a function supporting the main task. General manufacturing companies discovered this long ago, but pharmaceutical producers have been lagging. Once you consider the outsouring of non-core activities like facility management (FM), office services, space planning, and utilities management, you can focus on core business functions that make profits.

This approach can produce better results for less work than traditional validation methods. The statistics-based method called Design of Experiments (DoE) has a long history when applied to optimising a product or a process. This technique is well suited for running robustness trials as part of validation.

The sheer volume of research and drug discovery data can thwart efforts at integrating research knowledge. An automated database system with useful algorithms could help solve this problem.Information and Knowledge Management (KM) are crucial components in any life sciences research and development strategy. Without an effective information management strategy, there is little point in doing biological research.

Increasing titer can have a significant impact on the cost of goods sold. Case studies show that a fourfold improvement in titer reduces that cost by one-half.Cell culture productivity has increased dramatically over the last few decades.

This productivity increase is due in large part to significant process development efforts in this area, efforts traditionally justified by the economic benefit of improving productivity. The economic pressure to increase productivity has been highlighted in recent years by the success of monoclonal antibodies, some of which have market requirements in the hundred-kilogram-per-year range. The demand for such large quantities of protein has, in turn, triggered concerns about a potential shortage of manufacturing capacity, intensifying the pressure to boost cell culture productivity.Development scientists have responded to this challenge admirably.

During the past several years in the pharmaceutical and biopharmaceutical industries, conflicts and misunderstandings have arisen between companies and their contractors. Too often, productive working relationships have crumbled, resulting in expensive production delays with companies and contractors squabbling over their roles and responsibilities. Such conflicts may have their roots in the lack of a sound quality agreement (QAG). QAGs that clearly delineate good manufacturing practice (GMP) responsibilities between a sponsor and a contractor can help companies and their contractors avoid certain conflicts.