1. Raw Materials Disinfecting, autoclaving and discarding of waste material Cleaning of glassware, vessels and other small equipment/ material Chemical dispensary Small medium production Bulk medium production (bacterial vaccines) Viral medium production (viral vaccines) Ice-packs Key Challenges Recycling of glassware – cleaning validation challenge therefore need to move to disposable/single-use options Recycling of plasticware e.g. roller bottles – is a no, no for GMP Hand washing as opposed to washing machines to do the work – capital investment into new equipment needed | Onderstepoort Biological Products © |22nd February 2013Page 53 Washing Glassware Dispensary Viral medium Autoclaving/ Sterilization

2. Bacterial Vaccine Production 28 bacterial vaccines – batch production 6 diagnostic reagents Inactivated vaccines Live vaccines Multivalent products Combination products 2, 5, 10, 20, 50 and 100 and 500 dose pack sizes Bovine (cattle), Ovine (sheep), Caprine (goat), Avian (poultry), Equine, (horses) Fermentors – aerobic and anaerobic Key Challenges Full plant needs to be upgraded - new equipment and increased capacity, needed as current equipment is becoming redundant and difficult to maintain and not supported by original manufacturer, proper process and people flow, new or upgraded facility to accommodate new equipment (proper ventilation, access etc) No pilot plant facility and equipment | Onderstepoort Biological Products © |22nd February 2013Page 54 Pilot fermentor Production fermentors Pilot fermentor

3. | Onderstepoort Biological Products © |22nd February 2013Page 55

4. Viral Vaccine Production 13 viral vaccines - batch production Inactivated vaccines Live vaccines Multivalent products Combination product 1, 5, 20, 50, 100 and 500 dose pack sizes Bovine (cattle), Ovine (sheep), Caprine (goat), Avian (poultry), Equine (horses) Roller bottles – different primary and continuous cell lines Embryonated eggs Mostly open production system Key Challenges Open production processes, monolayers Lack of HVAC Older technology (roller bottles, bottles of medium – new biobags and bioreactors (suspension cells) Sharing of formulation room No pilot plant facility and equipment | Onderstepoort Biological Products © |22nd February 2013Page 56 Egg inoculation Closed system Open system Roller bottles

5. | Onderstepoort Biological Products © |22nd February 2013Page 57 Viral vaccine manufacturing – then and now….