Bangalore, 11 June 2020: Gangagen has so far been offering customized bacteriophage testing services as a non-GLP ( Good Laboratory Practice) Study to determine the presence or absence of phage contaminants in bacterial cell banks or production cells, said Dr Jagadeesh Bhat, lead-business development at Gangagen Biotechnologies.
Dr Bhat said Gangagen offers both lytic and lysogenic phage testing for E.coli cell lines. The phage testing is carried out using several positive and negative controls for each type of test. “  With our extensive experience in phage biology, we have developed specific set of E.coli strains for detecting presence of lytic and or lysogenic phages in E. coli cell bank strains. We have been providing this service on a regular basis for a number of well-known bio-pharmaceutical industry clients in India,” he added.
Dr Bhat explained the background on phage testing. The commercial production of recombinant biologicals and therapeutics is an important outcome of modern biotechnology. Selecting an ideal host bacterium to produce specific protein of interest is an important step in developing a production process. Widespread use of E. coli and other bacterial systems in biotechnology has led to the development of many different strains/cell lines. The process developed in production of therapeutics has to be taken to industrial scale to get viable industrial production mainly through fermentation technology.  
The starting material for manufacturing includes a well characterized bacterial culture, known to be free from bacteriophage and is capable of expressing the protein product of interest in good measure. Production host bacterial cell “seed lot” system is used by manufacturers to assure identity and purity of the starting raw material viz., production host culture. A cell seed lot/research cell bank consists of aliquots of a single culture from where the “Master Cell Bank” (MCB) and “Working Cell Bank” (WCB) are derived. A well-characterized cell bank assures lotto-lot consistency of the product. 
Regulatory agencies such as USFDA, EMEA require MCBs to adhere to ICH guidelines which emphasizes on characterization and testing to establish identity, purity and genetic stability of the cell line. A phage contaminated cell bank cannot be termed as ‘stable’ as it may not generate the required cell density in a sustainable fashion during the fermentation process because of contaminating phages. Thus, it becomes essential to establish absence of phages in cell banks by conducting the prescribed battery of tests.  
Phage contamination: Phage contaminations can be ubiquitous, unpredictable and presence of contaminating phage would pose most formidable problem. These contaminating phages can be liquid or air borne and the phages’ size and robust nature allows them to evade sterilization procedures at times. The presence of phages may also have an impact on long term stability of the cell bank. The impact of a phage contamination can vary from the slow growth to a dramatic total lysis of the producer organism in the fermenter.
 Decontamination is very difficult in large manufacturing facilities, and if a phage propagated in a bioreactor spreads throughout the plant, it can survive for a long period in the facility without being detected. Additionally, the problem caused by phages is also known to resurface, even after several months after the previous episode. 
References: 1. ICH Topic Q5D Quality of Biotechnological Products: Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/ Biological Products. 
2. FDA: Points to consider in the characterization of cell lines used to produce biologicals, 1993. 
3. FDA: Guidance for industry, Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications, 2010.

Bangalore based Gangagen Biotechnologies also plans to offer complete characterization of cell bank, that will include the phage testing as a GLP service shortly.