Reason cause For Major Batch Failures in BIO pharmaceutical Industry

1. Prepared by: Sandip Patel Group No: 2 Hemin Shah Munir Shah Hiren Patel Paresh Patel Rajeshkumar Patel

8. Source: Reference [18]

9. Source: Reference [7] # Culture Tested # Positive Netherlands 1,949 488 (25%) Czechoslovakia 327 121 (37%) Argentina 65% Japan 80+% Israel 32% # Cultures Tested # Positive FDA (1970’s to 1990’s) (11) 20,000 Cultures Tested Over 3000 (15%) Bionique Testing Laboratory (several years prior to 1993) (41) 11,000 Culture Tested 1218 (11.1%) Microbiological Associates (1985 to 1993) (13) 2,863 Culture Tested 370 (12.9%) American Type Culture Collection (ATCC) (1989 to 1994) (42) 5,362 Culture Tested 752 (14%)

16. Good Aseptic Techniques Strategic Use of Antibiotics Strategic Use of Cell Repository Good Housekeeping by Everyone Understanding Nature of Contamination Contamination Controlling Program Building Blocks for successfully managing cell culture contamination [7]

22. Disposable with Latest technologies Source: Reference [16] Element Technology use Addition information Company Disposable sensor oxygen, pH, and carbon dioxide sensors (fluromatrix technology) LEDs & photo-detectors. Inexpensive, useful for FDA imitative technology Sartorius Biotechnology Mixing Single Use Mixer Levitate and drive a disposable impeller inside a single-use bag. Scalability and reduced contamination, operating costs, and downtime associated with cleaning and validation of conventional mixing systems. LevTech, Hyclone Bag Flexel 3-D bag system Reduce contamination Applikon, SAFC Biosciences Sterile sampling Integrated one-way valve that prevents any of the withdrawn cell culture media sample returning to the main bioreactor. Reduce contamination Cellexus Sample

23. New Disposable Filling System Source: Reference [11]