Biopharmaceutical laboratory

Future trends in IA reside in several areas, including (a) new labels and improved sensitivity, (b) automation, (c) simultaneous multianalyte assays, and (d) genetic engineering. The trend must be to exploit the current advantages of IAs, which include sensitivity, simplicity, limited cost, and speed. Our goal must be to make the assays faster, better, and more accessible. However, it must be remembered that what is appropriate and acceptable in the clinical chemistry laboratory may not be acceptable or may be much less appropriate in the biopharmaceutical laboratory. Only trends that may apply to the pharmaceutical analyst will be discussed here. 

Four column systems are available from Amersham Pharmacia Biotech that can be used to pack SEC media for various applications at the laboratory scale. These include C, XK, SR, and HR column systems. All of the laboratory-scale columns are constructed with borosilicate glass tubes. Columns for larger scale process applications include INdEX, BPG, EineLINE, BPSS, and Stack columns. The larger scale columns are constructed to meet stringent validation requirements for the production of biopharmaceuticals. Each of the column types are described. 

As the twentieth century came to a close, the job market for computational chemists had recovered from the 1992-1994 debacle. In fact, demand for computational chemists leaped to new highs each year in the second half of the 1990s [135]. Most of the new jobs were in industry, and most of these industrial jobs were at pharmaceutical or biopharmaceutical companies. As we noted at the beginning of this chapter, in 1960 there were essentially no computational chemists in industry. But 40 years later, perhaps well over half of all computational chemists were working in pharmaceutical laboratories. The outlook for computational chemistry is therefore very much linked to the health of the pharmaceutical industry itself. Forces that adversely affect pharmaceutical companies will have a negative effect on the scientists who work there as well as at auxiliary companies such as software vendors that develop programs and databases for use in drug discovery and development. 

Biopharmaceutical proteins/Vaccines Gene Site erf Integration Promoter S /3 regulatory %tsp elements expression Laboratory... 

The upstream processing element of the manufacture of a batch of biopharmaceutical product begins with the removal of a single ampoule of the working cell bank. This vial is used to inoculate a small volume of sterile media, with subsequent incubation under appropriate conditions. This describes the growth of laboratory-scale starter cultures of the producer cell line. This starter culture is, in turn, used to inoculate a production-scale starter culture that is used to inoculate the production-scale bioreactor (Figure 5.7). The media composition and fermentation conditions required to... 

Figure 5.8 Typical industrial-scale fermentation equipment as employed in the biopharmaceutical sector (a). Control of the fermentation process is highly automated, with all fermentation parameters being adjusted by computer (b). Photographs (a) and (b) courtesy of SmithKline Beecham Biological Services, s.a., Belgium. Photograph (c) illustrates the inoculation of a laboratory-scale fermenter with recombinant microorganisms used in the production of a commercial interferon preparation. Photograph (c) courtesy of Pall Life Sciences, Dublin, Ireland...

Mira Symillides Laboratory of Biopharmaceutics Pharmacokinetics, National Kapodistrian University of Athens, Athens, Greece... 

Tim Wehr is Staff Scientist at Bio-Rad Laboratories in Hercules, California. He has more than 20 years of experience in biomolecule separations, including development of HPLC and capillary electrophoresis methods and instrumentation for separation of proteins, peptides, amino acids, and nucleic acids. He has also worked on development and validation of LC-MS methods for small molecules and biopharmaceuticals. He holds a B.S. degree from Whitman College, Walla Walla, Washington, and earned his Ph.D. from Oregon State University in Corvallis. 

Bioanalytical laboratories provide support for most of the activities at the biopharmaceutical company. They are responsible for characterizing the molecules in development, establishing and performing assays that aid in the optimization and reproducibility of the purification schemes, and optimizing the conditions for fermentation or cell culture, including product yields. Some of the characterization techniques will eventually be used in quality control to establish the purity, potency, and identity of the final formulation. 

Biopharmaceutical companies are highly diverse not only in their products but also in their size, capabilities, and approaches to development. Some biopharmaceutical companies (especially small companies) outsource part or most of the analytical work, some outsource manufacture and filling, and some invest and develop expertise to do everything in their own facilities. Most biotechnology companies are small, and sometimes it is faster and more cost-effective to outsource a task that requires expertise or expensive pieces of laboratory equipment not available in the company. Nevertheless, the analysts in the company will... 

Fortunately, protein concentration methods are relatively simple (low-tech) and inexpensive. The simplest assays require only a spectrophotometer calibrated for wavelength and absorbance accuracy, basic laboratory supplies, and good pipetting techniques. Protein concentration assays are quite sensitive, especially given the typical detection limits required for most biopharmaceuticals. 

In the development of new biopharmaceutical molecules, there is a constant need for analytical methods that provide critical information in areas that range from early characterization to routine analysis of approved products. Past experience indicates there are few projects in drug development that can be addressed by standard analytical procedures. Even well-established techniques often have to be modified to better suit the analysis of new samples. For this reason, a broad range of techniques is already an integral part of laboratories in the biopharmaceutical industry. 

DNLM 1. Pharmaceutical Preparations—analysis—Laboratory Manuals. 2. Biopharmaceutics—methods—Laboratory Manuals. 3. Chromatography—methods—Laboratory Manuals. 4. Electrophoresis—methods—Laboratory Manuals. 5. Spectrum Analysis-methods—Laboratory Manuals. QV 25 A5338 2005] I. Wehr, Tim. II. Rodnguez-Dlaz, Roberto. III. Tuck, Stephen (Stephen F.)... 

A diagrammatic representation of using PAT and the Laboratory Information Management System (LIMS) controls for the manufacturing of pharma-ceuticals/biopharmaceuticals is presented in Fig. 9.6. 

In the last two decades, CE has advanced significantly as a technique for biomolecular characterization. It has not only passed the transition from a laboratory curiosity to a mature instrument-based method for micro-scale separation, but has also emerged as an indispensable tool in the biotech and pharmaceutical industries (Chapter 14). CE has become a method of choice in R D for molecular characterization, and in QC for release of therapeutic biomolecules. In the biopharmaceutical industry, more and more CE methods have been validated to meet ICH requirements. To demonstrate the influence of CE in RScD for method development and in manufacturing for the release of therapeutic proteins and antibodies, examples from the pharmaceutical industry are provided in Chapter 14. 

Nicolas Andreotti is a Ph.D. student under the supervision of Dr. Sabatier at the ERT 62 laboratory. He also has a permanent position in a biopharmaceutical company. He works on animal peptide toxins and candidate drugs, and has contributed to approximately 10 scientific articles and 10 communications. 

Besmajouirou has a Ph.D. in neurosciences. She is affiliated to the ERT 62 laboratory and holds a position as a researcher in a biopharmaceutical company. She works in the field of animal toxins, antitumor compounds, and antivirals. She has contributed to 10 scientific articles, 6 communications, and 2 patents. 

Laboratory of Biopharmaceutics, Faculty of Pharmacy Airlangga University, Jl. Dharmawangsa dalam,... 

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