Repligen Corporation · NASDAQ:RGEN
Repligen — Technical Presentation (December 2019)
18 slides from Repligen's technical presentation, December 2019
Slide 1: Applications of Pre-Packed Columns in Scale Down Model and Viral Clearance Validation Studies
Repligen Seminar Series Applications of Pre-Packed Columns in Scale Down Model and Viral Clearance Validation Studies a customer and science-focused contract development & manufacturing organization
Slide 2: KBI Biopharma: Who we are
KBI Biopharma: Who we are -Contract Development and Manufacturing Organization (CDMO) founded in 1997 -Excellent track record of delivering cell line, upstream/downstream process, analytical and formulation development solutions for our clients on a variety of different molecules. -Extensive experie
Slide 3: Where We Are - Global Presence
Where We Are- Global Presence KBI Offices San Diego, CA (2017) Alliance Protein Labs • Analytical Technologies • Leading AUC expertise Geneva, Switzerland (2017) Boulder Leuven Geneva Selexis (KBI affiliate) San Durham • Best-in-class Cell Line Diego RTP Development and variant screening The Woodlan
Slide 4: KBI-NC: Mammalian Process Development
KBI-NC: Mammalian Process Development • KBI has performed mammalian Process & Analytical Development for 50+ molecules • Successful on a wide variety of programs: enzymes, mAbs, vaccines and fusion proteins 12+ client INDs supported per year • Specific focus on First in Human mAb & non-mAb platforms
Slide 5: Lab Scale Columns in Early Phase DSPD
Lab Scale Columns in Early Phase DSPD Chromatography Process Phase I Viral Phase I Clinical Scale Down Model Resin Screening Condition Confirmation/Pilot Clearance Spiking Supply Qualification Evaluation Scale Assessment Studies Significant flexibility is required to identify suitable resins during
Slide 6: Lab Scale Columns in Early Phase DSPD
Lab Scale Columns in Early Phase DSPD Chromatography Process Phase I Viral Phase I Clinical Scale Down Model Resin Screening Condition Confirmation/Pilot Clearance Spiking Supply Qualification Evaluation Scale Assessment Studies In early phase development, lab scale columns (10 – 400 ml bed volume)
Slide 7: Repligen Valichrom Columns
Repligen Valichrom® Columns Repligen Valichrom columns can provide a time-saving alternative to self-packed columns in house once DSP resins have been selected. Advantages 0.5 – 2.5 cm internal diameters available provides flexibility for different bed volume needs 10 - 60 cm bed height range allows
Slide 8: Scale Down Model Assessment
Scale Down Model Assessment At KBI, incorporation of Valichrom columns has been highly beneficial at the stage where we establish our scale down model to support viral clearance validation studies. Scale down model assessment determines representativeness of lab scale operations relative to manufact
Slide 9: Scale Down Model and Manufacturing Scale Data: Example 1
Scale Down Model and Manufacturing Scale Data: Example 1 Parameter Scale Down GMP Production # of runs represented by average values 3 3 Column ID Valichrom 1.13 cm Opus 45 cm Yield (%) 72.3% 74.7% %HMW (SEC-HPLC) 2.0% 2.3% %LMW (SEC-HPLC) 0.3% 0.4% %Heterodimer (CEX-HPLC) 100% 100% Residual HCP (pp
Slide 10: Scale Down Model and Manufacturing Scale Data: Example 2
Scale Down Model and Manufacturing Scale Data: Example 2 Parameter Scale Down Pilot Scale GMP Production # of runs represented by average values 3 1 2 Column ID Valichrom 1.13 cm Opus 14 cm Opus 45 cm Yield (%) 98.2% 100% 94.7% %HMW (SEC-HPLC) 4.5% 6.5% 3.6% % Acidic Variants (WCX-HPLC) 43.5% 43.2%
Slide 11: Scale Down Model Takeaways
Scale Down Model Takeaways Scale down model verification using Valichrom columns has provided time savings relative to use of columns packed in-house. Confirmation of scale down model involves comparison of process performance and product quality parameters from lab to production scale systems. Scal
Slide 12: Viral Clearance Validation
Viral Clearance Validation Viral Clearance Validation targets a specific overall process Log Reduction of Virus (LRV) Typically the total LRV required from a DSP process is in the range of 12 – 20 LRV. Validation of viral clearance for at least one chromatography step will likely be required LRV val
Slide 13: Viral Clearance Validation
Viral Clearance Validation The scope of viral clearance validation studies depends on the status of the biologic in clinical trials Phase I studies 2 different viruses (e.g. XMuLV, MMV) Duplicate Chromatography experiments Phase III studies Expanded panel of viruses at least 4 (e.g. XMuLV, PRV, MMV,
Slide 14: Viral Clearance Validation: Columns Required
Viral Clearance Validation Chromatography Clinical Scale Down Virus Spike Run Total Columns Steps Validated Phase Columns Columns Required 1 I 1 4 5 3 I 3 12 15 1 III 1 8 9 3 III 3 24 27 -Minimum column number accounts only for columns used for one scale down column and viral clearance spiking study
Slide 15: Time Savings with Valichrom Pre-Packed Columns
Time Savings with Valichrom Pre-Packed Columns In 2016, KBI Biopharma executed >12 viral clearance studies in support of our client’s IND and BLA filings. Phase I and Phase III studies were included in this assessment Total columns required >200 columns. At 3 hours per column to pack, assess, saniti
Slide 16: Conclusions
Conclusions Pre-packed chromatography columns represent a significant time savings once DSP process resins have been defined Time savings is more significant as needs for lab scale columns increase in later stage programs (Process Characterization, Resin Lifetime Studies, etc…) Valichrom column pack
Slide 17: Acknowledgments
Acknowledgments Sigma Mostafa; Vice President, USPD and DSPD Yuan Chang; Director, DSPD Leslie Wolfe Ph.D.; Associate Director, DSPD Heather Horne Ph.D.; Senior Scientist, DSPD 17 Confidential
Slide 18: Questions? Contact Information
Questions? Contact Information Nate Nicholes Ph.D. Scientist II, DSPD Nnicholes@kbibiopharma.com My profile is also on LinkedIn 18 Confidential