Cell banks

Biotechnology feniientation/ cell culture Establishment of master cell bank and working cell bank Maintenance of working cell bank Cell culture and/or fermentation Isolation and purification Physical processing, and packaging... 

Goodwin Biotechnology, Inc. (GBI) is a fully integrated GMP contract manufacturer of mammalian cell products providing process development (upstream and downstream) and cell banking through production, purification, and sterile fill. The downstream... 

Authentic cell lines can be obtained from the following certified cell banks ... 

Xu Y, Sato K, Konno T et al (2009) An on-chip living cell bank. Proc in Micro-TAS 2009 W82F... 

Possible contamination by chemical or biological substances is one of the most important concerns when producing pharmaceutical proteins. Plant cell cultures ensure the production of the desired protein in a controlled, sterile and sealed environment and can be adapted to cGMP conditions. Therefore, the risk of contamination is minimized and the production conditions can be modified more easily in a contained reactor than in the field. Another advantage is the ability to freeze plant suspension cells in liquid nitrogen [66, 67] so that master and working cell banks can be established, a prerequisite for cGMP procedures [68]. 

Upstream processing is deemed to commence when a single vial of the working cell bank system (see later) is taken from storage and the cells therein cultured in order to initiate the biosynthesis of a batch of product. The production process is deemed complete only when the final product is filled in its final containers and those containers have been labelled and placed in their final product packaging. 

The cell bank s construction design is normally two tiered, consisting of a master cell bank and a working cell bank (Figure 5.6). The master cell bank is constructed first, directly from a culture of the newly constructed production cell line. It can consist of several hundred individually stored ampoules. 

Figure 5.6 The master cell bank/working cell bank system. For simplicity, each bank shown above contains only five ampoules. In reality, each bank would likely consist of several hundred ampoules. Working cell bank number 2 will be generated from master cell bank vial number 2 only when working cell bank number 1 is...

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 5.7 Outline of the upstream processing stages involved in the production of a single batch of product. Initially, the contents of a single ampoule of the working cell bank (a) are used to inoculate a few hundred millilitres of media (b). After growth, this laboratory-scale starter culture is used to inoculate several litres/tens of litres of media present in a small bioreactor (c). This production-scale starter culture is used to inoculate the production-scale bioreactor (d), which often contains several thousands/tens of thousands litres of media. This process is equally applicable to prokaryotic or eukaryotic-based producer cell lines, although the bioreactor design, conditions of growth, etc., will differ in these two instances...

An electrolytic cell bank producing a commercial product consists of m number of cell units. Due to various reasons (e.g., imperfect... 

A typical distribution is portrayed in Table 11 for a configuration of fifty cells arranged in five ten-cell banks, where for the sake of safety, a short-circuited cell will disconnect an entire bank. This arrangement is essentially identical to a five-cell bank with single short-circuits. The more efficient (i.e., the faster) the repair service (i.e., the smaller X/p), the smaller the probability that short-circuited cells are not repaired at any arbitrary time. Conversely, if repair takes a long time, a certain number of cells will always be short-circuited, and if kip is extremely large, a complete shutdown of cell operation will be highly probable (the Xlp = 10, ps 0.9 case is a case in point, albeit not overly realistic.)... 

Table 12 illustrates the computation procedure in the case of m = 5 the plant may be envisaged, as in Section V.l, to consist of m cell banks, the quantity j denoting the number of banks switched back into operation. In the specific case of X = p (equi -probability of switching into either direction), Eq. (47) reduces to the binomial probability distribution of selecting j elements out of m identical elements with a single-event probability of xh. 

In the froth flotation cell used for coal washing, illustrated in Figure 1.48, the suspension contains about 10 per cent of solids, together with the necessary reagents. The liquid flows along the cell bank and passes over a weir, and directly enters the unit via a feed pipe and feed hood. Liquor is discharged radially from the impeller, through the diffuser, and... 

There are four different drug products under Part II chemical active substance(s), radiopharmaceutical products, biological medicinal products, and vegetable medicinal products. For example, the GMP production report for biological medicinal products includes description of the genes used, strain of cell line, cell bank system, fermentation and harvesting, purification, characterization, analytical method development, process validation, impurities, and batch analysis (GMP production of biopharmaceuticals is described in Chapter 10). A DMF (Exhibit 8.8) is submitted. 

Cell Bank Maintenance and Record Keeping Cell Culture/Fermentation Harvesting, Isolation, and Purification Viral Removal/Inactivation Steps APIs for Use in Clinical Trials General Quality... 

Master Cell Bank and Working Cell Bank Origin... 

Cell Bank Records must be kept of the cell banking method and procedure. 

Characterization and Testing of Cell Banks Test for adventitious agents, endogenous agents, and molecular contaminants (toxins, antibiotics) to confirm identity, purity, and suitability for manufacturing use... 

Cells grow from a single vial (1-5 mL) to thousands of liters in bioreactors. Many generations of cell division and growth are involved. It is important that in this process, which may last from weeks to months, the cells do not mutate and faithfully express the intended protein. Cells at the completion of production are collected as samples and grown further as an end of production cell bank (EPCB). Analysis conducted on the products from the EPCB is to verify that the protein is produced properly, even after many generations of cell reproductions. 

The need to transport temperature-sensitive raw materials and products, such as cell line, medium, large molecule drugs, and vaccines, means that some form of control during transportation is needed. For example, a working cell bank for the production of proteins may be transported in liquid nitrogen (-196 °C) and that of protein and vaccines in dry ice (-78 °C) in order to protect the integrity of the materials. Data loggers are used to record the temperature... 

Discuss the importance of testing and characterizing cell lines and cell banks. 

Establishment Inspection Report Establishment License Application enzyme linked immunosorbent assay European Medicines Agency Environmental Protection Agency European Public Assessment Report end of production cell bank erythropoietin... 

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