16. Late 80’s The dawn of automation Simple semi manual fermentors Validation becoming more involved Containment being actively pursued CIP/SIP systems becoming more complicated Automation seen as reducing Headcount, Turn-round time Operator errors 5
18. Early 90’s Some companies begin to realise complex automation systems have drawbacks. They see increasing Headcount Complexity of plant Turn-round times Complexity of investigations (variables) Facility build costs Facility construction times 7
19. Early 90’s Example of early 90’s Bioreactor Additive manifold Air Out Air to headspace Air to sparger Jacket heat exchanger Sample device 8
21. Late 90’s to 2006 Some companies start to reduce cost by simplifying. Stainless steel reactors are simplified by reducing numbers of valves/items. Disposables reduce the need for CIP/SIP. Innovations Tubing welders Lynx valves Pod filters Wave reactors SUM’s 10
22. The fastest CIP? Reduce the number of inlets that need cleaning. How to simplify stainless vessels 11
27. How to simplify stainless vessels 16 Number of sterile boundary elastomers Pre Lynx Modifications Approximately 70 Post Lynx modifications Approximately 30
30. Present day Elan’s plant design breaks new ground (2008). Large scale disposables are widely accepted 2000L reactors are launched onto the market (2010) 19
32. The Facility – the next generation of plant after élan 2g/l monoclonal antibody- fed batch 10 x 4,000L batches per month 80 cm column, 3 cycles = 2 x 12,000L stainless plant 21
33. The Facility – The next generation after Élan Foot print Comparison Purification Bioreactors. X X Buffer prep. Media prep. 22
34. The Facility – the next generation of plant after élan How do you make media next to the bioreactor without contaminating the room with powder? 23
38. Use of Buffer towers in Downstream worked example 27
39. The Facility – the next generation of plant after élan How do you make and store up to 6,000L of buffer and not use large numbers of buffer bags? 28
40. Buffer towers - Prototype Answer By positioning 2,000L buffer towers close to the column and ‘topping up’ from 1,000L single use mixers. Prototype 29
41. Buffer towers - worked example Buffer Modeling Buffer storage in 1000L Buffer hold bags VS Five 2,000L buffer towers; replaced monthly Buffer b Adsorption chromatography buffer - Max 4,000L Buffer a UltrafiltrationDiafiltration buffer – Max 6,000L 30
42. The Facility – the next generation of plant after élan Buffer b Buffer a 31
45. The Facility – the next generation of plant after élan Cell Culture 12 technicians – 9:00 to 5:30 – 7 days a week Purification 24-36 technicians – 24hr – 7 days a week Buffer - Media 0 technicians HR 1 manager – 1 admin. QC No change from current factories Maintenance 1 HVAC, 1 Utilities, 2 Equipment/Cal Plant Automation 0 IT 3-4, Electronic batch records preferable Stores Same as current factories 34
52. Industry trends and expectations Reduced facility footprint Reduced production costs Decreasedcapitalinvestments More flexibleplantswith faster turnaround time Risk management and mitigation Increasedcontrol over products, processes, timelines Close cooperation, partnership, strategic alliances Culturewith a continuousimprovementsmindset Source: www.contractpharma.com, articleOctober 2010: Biotechnology Trends & Outsourcing, Lou Schmukler and John Korte, Pfizer Global Manufacturing Single use 41
53. What next at CMC…….. Installation of 2000L disposable Bioreactor/Harvest capacity in 2011 42