SUBCONTRACT DELIVERABLES. Table 1 summarizes documents and other deliverables due to SAIC at the indicated time points. 1 Technical Reports (technology transfer and engineering runs) Draft: 3 weeks following completion of transfer run Final: 2 weeks after receipt of SAIC comments PDF or Word document 2 Technical Remaining non-GMP [*] product (technology transfer and engineering runs) including cell paste interim reference material, and lysates Within a week of completion Sent to SAIC designee in proper shipping containers with a temperature monitor in each container 3 Technical cGMP master BPRs Draft: 4 weeks before initiation Final: 2 weeks after receipt of SAIC comments PDF or Word document 4 Technical Completed rCSP cGMP BPRs Draft: 3 weeks following completion of 100 L cGMP run Final: 2 weeks after receipt of SAIC comments PDF or Word document [*] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions. 5 Technical [*] along with associated raw data Draft: 3 weeks following completion of cGMP rPfCSP DS release testing Final: 2 weeks after receipt of SAIC comments PDF or Word document 6 Technical [*] Within a week of completion Sent to SAIC designee in proper shipping containers with a temperature monitor 7 Technical Remaining cGMP unpurified cell paste and or lysate Maintain GMP chain Stored at Pfenex CMO in proper GMP storage conditions 8 Technical Interim reports and a final stability report for the [*] stability monitoring Draft: 3 weeks following completion of each time point Final: 2 weeks after receipt of SAIC comments PDF or Word document 9 Reporting Biweekly meeting and minutes Meeting as scheduled, minutes within a week of the meeting Teleconference 10 Reporting Monthly reports, including technical progress, and budgeting updates Due by the 15th of each month during the performance of work efforts PDF or Word document 11 Technical Regulatory support documents Draft: 3 weeks following completion of all activities Final: 2 weeks after receipt of SAIC comments Draft: Word document Final: Signed Pdf 12 Reporting Inventory Tracking Report, including banked production materials, reagents, held intermediates and Drug Substance Due by the 15th of each month during the performance of work efforts PDF or Word document [*] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions. # Step and Parameters The process flow sheet is based on purifying 5 L fermentation and projected downstream process after development Inoculum - batch Seed broth volume Fermentation time 0 6 L ~24 h Fermentation 2 i 1 Production - high density fed-batch Production broth volume Fermentation time Expression ▇▇▇▇▇ ▇▇ ▇ ~▇▇ h 4 g/L 3-4 g/L 2 Production - high density fed-batch Broth aliquot volume Relative Centrifugation Force Centrifugation Temperature Centrifugation Time 1 L, cpy = 10 15900 × g 4°C 60 min Cell Reconstruction i Hold (-80°C) [*] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions. 4 Cell Lysis i 2C g (per cycle) Feed Equipment Flush buffer Flush buffer amount Homogenization parameter Lysate temperature Number of passes Lysis time Step yield 14 L approximate from step 3 Niro Soayi 2M urea, 20mM Tris, pH 8.2 As needed TBD (critical parameter) Codec to < 12°C with heat exchanger at outlet) 1 pass 1.4 hr approximate (at ~ 0 L/hr) 100% 20% cell lysate: pH, Cond Retain for SDS-PAGE/CGE 5 Dilution of 20% lysate to 10% solids 2C g (per cycle) Feed Feed volume Equipment Dilution buffer Dilution buffer amount Total volume upon dilution Pump rate Mix time Step yield Lysate from step 4 ▇▇ ▇ ▇▇ ▇ single use bag Sartorius Stedim 2M urea, 20mM tris, PH 8 14 L approximate 28 L approximate 8 L/min > 10 min 100% 10% cell lysate: pH, Cond Retain for SDS-PAGE/CGE 6 Disk-Stack Centrifugation i 2C g (per cycle) Feed Feed volume Feed Temp Equipment G-force Flow rate 10% lysate from step 5 28 L 15 – 26 °C Westfalia SC -6 15,000 g 0.3 L/mh Centrate turbidity (HACH NTU as well as ▇▇▇▇▇▇ equipment measurement) Q/S 8.10E-10 m/s Backpressure Discharge Interval Discharge Volume Centrate Temp Step Time Step yield 75-82 psi 20 min 0.7 L <20°C, cooled by heat exchanger on the outlet 1.6 hrs 88% 7 Depth Filtration i 16 g (per cycle) Feed Feed volume Equipment Manufacturer Part # Centrate from Step 6 24.64 L Millistak+XOHC Depth Filter Millipore MXOHC05=S1 Depth Filter Equilibration: pH, cond [*] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions. Quantity Filter Area Filter Loading Flowrate Step time Step yield 1 0.22 m2 112 L/m 2 33 – 50 LM-I 0.12 – 0.18 l/min 1 hr, run in parallel with centrugation 95%
Appears in 1 contract
Sources: Subcontract Agreement (Pfenex Inc.)
SUBCONTRACT DELIVERABLES. Table 1 summarizes documents and other deliverables due to SAIC at the indicated time points. 1 Technical Reports (technology transfer and engineering runs) Draft: 3 weeks following completion of transfer run Final: 2 weeks after receipt of SAIC comments PDF or Word document 2 Technical Remaining non-GMP [*] product (technology transfer and engineering runs) including cell paste interim reference material, and lysates Within a week of completion Sent to SAIC designee in proper shipping containers with a temperature monitor in each container 3 Technical cGMP master BPRs Draft: 4 weeks before initiation Final: 2 weeks after receipt of SAIC comments PDF or Word document 4 Technical Completed rCSP cGMP BPRs Draft: 3 weeks following completion of 100 L cGMP run Final: 2 weeks after receipt of SAIC comments PDF or Word document [*] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions. 5 Technical [*] along with associated raw data Draft: 3 weeks following completion of cGMP rPfCSP DS release testing Final: 2 weeks after receipt of SAIC comments PDF or Word document 6 Technical [*] Within a week of completion Sent to SAIC designee in proper shipping containers with a temperature monitor 7 Technical Remaining cGMP unpurified cell paste and or lysate Maintain GMP chain Stored at Pfenex CMO in proper GMP storage conditions 8 Technical Interim reports and a final stability report for the [*] stability monitoring Draft: 3 weeks following completion of each time point Final: 2 weeks after receipt of SAIC comments PDF or Word document 9 Reporting Biweekly meeting and minutes Meeting as scheduled, minutes within a week of the meeting Teleconference 10 Reporting Monthly reports, including technical progress, and budgeting updates Due by the 15th of each month during the performance of work efforts PDF or Word document 11 Technical Regulatory support documents Draft: 3 weeks following completion of all activities Final: 2 weeks after receipt of SAIC comments Draft: Word document Final: Signed Pdf 12 Reporting Inventory Tracking Report, including banked production materials, reagents, held intermediates and Drug Substance Due by the 15th of each month during the performance of work efforts PDF or Word document [*] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions. # Step and Parameters The process flow sheet is based on purifying 5 L fermentation and projected downstream process after development Inoculum - batch Seed broth volume Fermentation time 0 6 L ~24 h Fermentation 2 i 1 Production - high density fed-batch Production broth volume Fermentation time Expression ▇▇▇▇▇ ▇▇ ▇ ~▇▇ h 4 g/L 3-4 g/L 2 Production - high density fed-batch Broth aliquot volume Relative Centrifugation Force Centrifugation Temperature Centrifugation Time 1 L, cpy = 10 15900 × g 4°C 60 min Cell Reconstruction i Hold (-80°C) [*] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions. 4 Cell Lysis i 2C g (per cycle) Feed Equipment Flush buffer Flush buffer amount Homogenization parameter Lysate temperature Number of passes Lysis time Step yield 14 L approximate from step 3 Niro Soayi 2M urea, 20mM Tris, pH 8.2 As needed TBD (critical parameter) Codec to < 12°C with heat exchanger at outlet) 1 pass 1.4 hr approximate (at ~ 0 L/hr) 100% 20% cell lysate: pH, Cond Retain for SDS-PAGE/CGE 5 Dilution of 20% lysate to 10% solids 2C g (per cycle) Feed Feed volume Equipment Dilution buffer Dilution buffer amount Total volume upon dilution Pump rate Mix time Step yield Lysate from step 4 ▇▇ ▇ ▇▇ ▇ single use bag Sartorius Stedim 2M urea, 20mM tris, PH 8 14 L approximate 28 L approximate 8 L/min > 10 min 100% 10% cell lysate: pH, Cond Retain for SDS-PAGE/CGE 6 Disk-Stack Centrifugation i 2C g (per cycle) Feed Feed volume Feed Temp Equipment G-force Flow rate 10% lysate from step 5 28 L 15 – 26 °C Westfalia SC -6 15,000 g 0.3 L/mh Centrate turbidity (HACH NTU as well as ▇▇▇▇▇▇ equipment measurement) Q/S 8.10E-10 m/s Backpressure Discharge Interval Discharge Volume Centrate Temp Step Time Step yield 75-82 psi 20 min 0.7 L <20°C, cooled by heat exchanger on the outlet 1.6 hrs 88% 7 Depth Filtration i 16 g (per cycle) Feed Feed volume Equipment Manufacturer Part # Centrate from Step 6 24.64 L Millistak+XOHC Depth Filter Millipore MXOHC05=S1 Depth Filter Equilibration: pH, cond [*] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions. Quantity Filter Area Filter Loading Flowrate Step time Step yield 1 0.22 m2 112 L/m 2 33 – 50 LM-I 0.12 – 0.18 l/min 1 hr, run in parallel with centrugation 95%
Appears in 1 contract
Sources: Subcontract Agreement (Pfenex Inc.)