These viruses are not subject to any specific testing for adventitious viruses. The corresponding vaccine must be manufactured, tested

and distributed within only a few months in order to meet vaccination schedules [20], [21] and [22]. Because of this short timeline, conventional broad spectrum testing of the influenza virus seed for adventitious agents cannot be performed in time, Cabozantinib price particularly if one considers that months may be needed to prepare virus from an independent source and specific antibodies against the same to neutralise the influenza virus. For conventional egg-derived viral seeds it is commonly assumed and supported by historical safety records, that many adventitious viruses are removed by egg passages. Because cell-derived influenza virus isolates Wnt inhibitor are now being considered for use as starting material for vaccine manufacture, information

is needed about the behaviour of adventitious viruses during cultivation of influenza viruses in suitable cell substrates. Our studies contribute such information for a cell line that is qualified for influenza vaccine manufacture. The result presented here should be seen in context with specifically designed growth studies with a wide range of potentially contaminating viruses, which, along with the results of a systematic literature search on growth of viruses in MDCK cells, have been published previously, [8] and [9]. In those studies a standard amount of 106 infectious units (TCID50) per 100 ml culture was inoculated not into MDCK 33016 cells and the cells were grown for at least 14 days (21 days for slow-growing viruses) in CDM growth medium. High dilution passaging was avoided but samples of suspended cells and medium were taken at regular intervals to be tested for the virus, and an adequate amount of fresh medium was added after sampling to maintain cell growth. The agents studied included: three human adenovirus (types 1, 5, 6), herpes simplex virus (HSV), Epstein–Barr virus, cytomegalovirus, parainfluenzavirus 3 and SV-5, respiratory syncytial virus (RSV) type A and B, human coronavirus 229E,

human enterovirus species (Coxsackie A16, Coxsackie B30, Echovirus 6, poliovirus type 1), two human metapneumo virus strains, three different rhinoviruses, mammalian reovirus-3, BK polyomavirus, simian virus 40 (SV-40), budgerigar fledgling disease polyomavirus, avian C-type retrovirus (Rous sarcoma virus), avian infectious bursal disease birnavirus, two avian reovirus strains, minute virus of mice (MVM) parvovirus and porcine circovirus. Furthermore, the growth of Mycoplasma hyorhinis and Chlamydia trachomatis were assessed. In those studies high virus growth was observed for parainfluenzavirus 3, SV5 and herpes simplex virus, slow growth was seen with mammalian reovirus 3, and questionable results (very low or no growth) were noted for the two avian reovirus. No growth was observed for the other viruses and agents tested.