OPUS Pre-packed Chromatography Columns

Transcription

1 OPUS Pre-packed Chromatography Columns Fletcher Malcom Director, Product Management 18 October 2017

2 Pre-packed column innovation at Repligen leads to no compromise configurability The pre-packed column journey at Repligen leads to widespread adoption Partnered with Bioflash (origin of Repligen pre-packed columns) Launched OPUS 20 OPUS 30 for GMP manufacturing Launched OPUS 10 OPUS 14 OPUS 25 Launched OPUS 45 OPUS 5 Opened new OPUS ISO 7 Packing Suites 1 and 2, and 1 ISO 8 Prep Space in Waltham, MA Launched OPUS 60 Added OPUS PD for process development with Atoll acquisition Opened Packing Suites 3, 4, and 5 in Waltham, MA First OPUS 45 and 60 used for commercial Launched OPUS R with resin unpacking port Opened Packing Suites 6 and 7 in Waltham, MA 2 First range of configurable pre-packed columns for GMP manufacturing First pre-packed columns sized for 1000L and 2000L harvests First column to have an integral side-port design for resin removal Three industrial design awards

3 Number of experiments Scalable chromatography with OPUS Pre- Packed columns 50uL 85L OPUS RoboColumn DoE OPUS MiniChrom OPUS ValiChrom Process knowledge Scalable chromatography, efficient development workflows HTPD Screen very large numbers of input parameters Narrow the range of input parameters to further define the process Predictable Scale-up and control µl ml L 3 Cost per experiment

4 OPUS process development pre-packed columns for all of your chromatogaphy needs Resin screening to process validation Any resin, any application, any size Designed for process development and process validation, including viral clearance, scale-up, and sample preparation Over 300 resins packed OPUS RoboColumn for automated parallel chromatography OPUS MiniChrom for process development and sample preparation OPUS ValiChrom for process validation 4

5 OPUS ValiChrom matches the bed height of production scale columns with a precision of 1mm OPUS 45 Viral Validation Process Validation Height = 20 cm 5

6 Reproducible packed bed performance for robust validation Superimposition of HETP curves from 16 ValiChrom columns <9% variance of column quality attributes Elution Volume (V E ) [ml] ± 1.37 (4.16 %) Asymmetry (A S ) 0.92 ± 0.08 (8.70 %) OPUS ValiChrom for process validation or viral validation Theoretical Plates (N) [N/m] 2786 ± 229 (8.22 %) Column ValiChrom 1.6x16cm (32mL CV) Sample 500 μl, 1% Acetone (v/v) Linear velocity [cm/h] Elution Buffer 50 mm TRIS, 0.9 % NaCl; ph 8

7 OPUS Pre-packed Chromatography Columns Any resin, any application, any size Leader in pre-packed columns, multiple industrial design excellence awards Pre-packed chromatography columns with unparalleled flexibility in media choice, application, and size Expert in packing manufacturing-scale columns >150 45s and 60s shipped since 2015 > cm columns shipped since s of pre-packed columns shipped globally each year (>0.5cm ID) >100 different resins packed (5-60cm IDs) >100 Phase 1-3 campaigns and 1 commercial process since launch in 2012 Increase process efficiency Optimize process economics Quality and risk mitigation Most flexible in resin choice, application, and size (0.5-60cm IDs) Up to 35% cost savings over selfpacked columns No column packing failures Ready-to-use and disposable no cleaning validation process Up to 150 FTE hours savings per campaign ISO 9001 quality manufacturing 7 Faster campaign turnarounds No upfront capital expense Complete documentation package for GMP use

8 Scalable diameters from 0.5 to 60 cm ID Diameters OPUS Process Development OPUS RoboColumn OPUS MiniChrom OPUS ValiChrom OPUS PD 0.5 cm 0.5, 0.8, 1.13 cm 0.5, 0.8, 1.13, 1.16, 2.5 cm 5 cm 14 industry standard diameters OPUS Pre-GMP and GMP Run Ready OPUS 5 OPUS 8 OPUS 10 OPUS 14 OPUS 20 OPUS 25 OPUS 30 OPUS 45R OPUS 60R 8

9 Configurable bed heights from 5 to 30 cm Bed Heights OPUS Process Development OPUS RoboColumn OPUS MiniChrom OPUS ValiChrom OPUS PD cm cm cm 5 30 cm OPUS Pre-GMP and GMP Run Ready OPUS 5 OPUS 8 OPUS 10 OPUS 14 OPUS 20 OPUS 25 OPUS 30 OPUS 45R OPUS 60R 5 30cm Bed Heights 9

10 Packed with any resin Over 100 resins packed Affinity Partial List of Resins Packed: OPUS 5 60R IEX/Mixed Mode Resin 10 CaptivA MabSelect SuRe LX MabSelect SuRe MabSelect MabCapture A Eshmuno A Amsphere A3 KanCap A POROS CaptureSelect AAV9 AVB Sepharose HP POROS HQ50, HS50, XS Capto Impres, SP and Q Capto Impres, Adhere, MMC Capto Q, S, DEAE, Phenyl Capto Adhere, MMC SP Sepharose FF and HP Q Sepharose FF and HP Phenyl Sepharose FF, HP DEAE Sepharose FF Butyl Sepharose FF and HP Fractogel TMAE, SO3-, COO, DEAE Fractogel TMAE, SE HiCap Eshmuno CPX, HCX Toyopearl 650M, Butyl, Phenyl, DEAE, Super Q Toyopearl 600M, Butyl, Phenyl, PPG Nuvia S, cprime UNOsphere S, Q

11 Broadest range of pre-packed columns from bench- to productionscale OPUS Pre-packed Columns Diameter Bed Height Resin Platformable 11

12 Proven/tested column design Inlet (Polypropylene) OPUS 45 with press fit technology Top cap (ABS plastic) Outlet (Polypropylene) Tube (45 & 60 cm IDs: PP/E glass composite) (10 30 cm IDs: Polypropylene) Side-guard (ABS plastic) Class VI, EMEA 410/01 compliant materials of construction Flow Distributor and 12 μm mesh (Polypropylene) O-rings (Platinum cured silicone) 12 Return Line (Platinum cured silicone braided tubing) Bottom cap (ABS plastic) Casters (polyamide hub, polyurethane tires)

13 State of the art packing facility in Waltham, MA USA OPUS packing suite capabilities Automated parts washer Validated cleaning protocols 1 large ISO 8 classified buffer prep room Controlled packing and testing environment 7 ISO 7 classified packing rooms Capacity for >800 columns per year (1 shift operation) 7 custom-configured packing stands 1 multi-diameter packing stand per room Axial compression and/or flow packing 4 custom-configured chromatography skids Plate count, asymmetry, pressure-flow testing Improved process monitoring and documentation 13

14 Certificate of Analysis delivers critical fit for purpose information Product Identification Column specifications (ID, BH, lot #, serial #, PN) Resin type and lot number Shipping solution Pack date Quality Control Release Data Regulatory / quality compliance Theoretical plates / meter result Asymmetry result Bioburden and Endotoxin (GMP Run Ready only) Chromatogram and test method (page two) Quality Assurance Information ISO 9001 certified Product Contact Material Statement Manufacturing environment Chromatography resin control Attachments Resin Manufacturer s CoA 14

15 OPUS 45R and OPUS 60R Ultimate flexibility from pre-packed to unpacked

16 OPUS R Columns with unpacking capability OPUS 45R and 60R Columns OPUS 45/60cm column with a side port to enable resin unpacking in <5CVs Tubing accessories included Easy removal of resin without deconstructing the column Supporting (non-supplied) equipment includes a quaternary flow pump and slurry tank Port designed to have no impact on chromatographic performance or cleanability of packed bed Use unpacked resin for process development or as a back-up strategy for manufacturing in the event of a deviation 16

17 Resin removal in < 5CVs OPUS 45R Tubing set configuration and diagram for unpacking V5 No column deconstruction required Pump P V1 V2 V4 V3 Chrom System/ Waste Inlet Outlet V6 Resin Collection Tank Sepharose 6FF and POROS resin Play video Step Description CVs (POROS) 1 Resin flush, flow into inlet and outlet 1 2 Slurry flush, air sparge/purge Pre-packed Resin Sepharose 6 FF Resin Yield (45.7 x 20 cm) 99% (39.1L of 39.4) Residual Volume 3 CV (95L) 3,4 Column Rinse 1, fill (buffer), slurry flush , 6 Column Rinse 2, fill, slurry flush 0.75 POROS 99% (39.1 of 39.4) 3.25 CV (104L) 7, 8 Column Rinse 3, Fill, slurry flush Total Volume 3.25 CV

18 OPUS R Columns maintain chromatographic performance Chromatographic performance HETP (N/m) Asymmetry 45 cm standard R cm with unpacking port cm standard R cm with unpacking port Sepharose 6 Fast Flow, 20 cm bed height OPUS 45R Column Qualification Peak OPUS 60R Column Qualification Peak cm/hour with 1% CV of 10% Acetone injection

19 Bioburden challenge shows columns are cleanable and easily sanitized Bioburden Challenge OPUS 45R OPUS 60R Cleaning Step/Measurement Water effluent after overnight E.coli incubation Water effluent post sanitization effluent Bioburden (CFU/mL) Endotoxin (EU/mL) Bioburden (CFU/mL) Endotoxin (EU/mL) TNTC > 0.25 TNTC > < < Method OPUS 45R (20cm bh) and OPUS 60R (20cm bh) Sepharose 6FF columns packed and qualified Columns saturated with 1CV E. coli (absorbance & incubated overnight at room temperature Flushed with 3CVs water and sampled column effluent Sanitized Flush with 1M sodium hydroxide in up-flow at 100cm/h for 30 minutes then down-flow at 100cm/h for 30 minutes Recirculate 1M sodium hydroxide for 2 hours in up-flow at 100cm/h Incubate the column in 1M sodium hydroxide for 1 hour (static sanitization for compete removal of endotoxins) Flush with water until neutral ph is achieved Incubated at room temperature overnight Samples collected and tested for bioburden & endotoxin

20 OPUS R Columns maintain performance after worst case shipping simulation OPUS 60R shipping validation During the ISTA test (procedure 2B) the column was subjected to the following conditions: High temperature (38 C) and high humidity for 36 hours Low temperature (4 C) for 36 hours Compression testing (2836 lbs, or 1286 kgs on top of crate) 2 hours of random vibrational testing 6 drop tests 4 incline impact tests Asymmetry Pre-shipping Post-shipping Plate Count (N/m) Pre-shipping Post-shipping

21 Ultimate flexibility from pre-packed to unpacked Innovative side port for simple resin removal Performance and cleanability maintained OPUS 45R and 60R Columns Mitigates process risk Learn more at 45R_60R 21

22 22 Wrap-up and Conclusions

23 Comprehensive model for column packing process flow Using pre-packed columns eliminates many steps IQ/OQ & documentation Column packing buffer prep Resin prep (define) Column packing documentation vs. Column packing Column unpacking Unpacked column cleaning Cleaning verification (unpacked column) 23

24 Model Outputs: ~140 FTE hours and ~2-3 suite days saved per project per column Worst case scenario ~10yr fixed cost depreciation for multiproduct self-pack columns, BPG or Chromaflow style 1 time project use for pre-packed column 24

25 OPUS Pre-packed Chromatography Columns OPUS = Open Platform User Specified Pre-packed chromatography columns with unparalleled flexibility in resin choice and size Experts in column packing Thousands of columns shipped globally each year Largest range of pre-packed columns available 50ul 85L Used in 100+ Phase 1-3 processes and 1 commercial process since

26 Fletcher Malcom Director, Product Management Repligen Corporation 2017 Repligen Corporation. All rights reserved. The trademarks mentioned herein are the property of Repligen Corporation and/or its affiliate(s) or their respective owners.