/

333 344

/ 332 03-6264-066003-6264-0663 03-6264-0620

334 LAL 335 336 LAL 338 QCL-1000 LAL 33 LAL 340 C 341 LAL 343 ELx808 344 FLx800 345 PyroTec 346 WinKQCL 347 CSE 348 / 03-6264-066003-6264-0663 03-6264-0620 333

Pyrogen 160 Levin Bang 170 Limulus polyphemus amebocyte lysate LAL / www.lonza.com/lal 334 03-6264-066003-6264-0663 03-6264-0620

LAL Routine Positive Product Control PPC WinKQCL PPC / Inhibition/Enhancement / Positive Product Control PPC WinKQCL PPC Initial Qualification LAL 3 2 0.5λ 0.80 / 03-6264-066003-6264-0663 03-6264-0620 335

/ LAL 0.03 EU/mL / LAL 336 03-6264-066003-6264-0663 03-6264-0620

-QCL LAL 0.005 EU/mL LAL -5000 LAL 0.01 EU/mL QCL-1000 LAL 0.1 EU/mL 16 rfc 0.005 EU/mL LAL FDA, EDQM LAL / 03-6264-066003-6264-0663 03-6264-0620 337

405 410 nm Kinetic-QCL 6 37, 405 410 nm WinKQCL / Kinetic-QCL LAL Kinetic-QCL 0.005 50 EU/ml CSE ELx808 WinKQCL 6 CSE EU/ml K50-643J Kinetic-QCL 12 CSE, Kinetic-QCL Kinetic Chromogenic LAL Assay (without CSE) 12 tests 12 24 / 8 0.005 50 108,000 CSE EU/ml 001016 Kinetic-QCL 12 Kinetic-QCL Kinetic Chromogenic LAL Assay (without CSE) 12 tests 12 24 / 8 (30 ml) 3 CSE 2 0.005 50 118,000 338 03-6264-066003-6264-0663 03-6264-0620

QCL-1000 QCL-1000 6 JP-RSE, CSE 405 410 nm QCL-1000 LAL FDA LAL 0.1 1.0 EU/ml 16 ELx808 6 CSE EU/ml 0010166 QCL-1000 120 QCL-1000 Endpoint Chromogenic LAL Assay 120 24 / 5 2 (30 ml) 2 CSE 1 0.1 1 75,000 / 03-6264-066003-6264-0663 03-6264-0620 33

340 nm PYROGENT -50006 37, 340 nm WinKQCL / PYROGENT -5000 LAL 0.01 100 EU/ml CSE ELx808 WinKQCL 6 CSE EU/ml N385-8J 5000 200 CSE PYROGENT -5000 Kinetic Turbidimetric LAL Assay (without CSE) 200 tests 200 50 / 4 4 0.01 100 65,000 CSE EU/ml 0010233 5000 100 PYROGENT -5000 Kinetic Turbidimetric LAL Assay (with CSE) 100 tests 100 50 / 2 2 CSE 1 0.01 100 35,000 340 03-6264-066003-6264-0663 03-6264-0620

rfc LAL ( ) C Pyro Gene rfc 380 nm 440 nm rfc rfc 372 WinKQCL 0.005 5 EU/mL FDA, EDQM LAL Pyro Gene rfc Pyro GeneTM rfc LAL C rfc C LAL ELx800 WinKQCL 6 CSE Avg Net Delta RFU 10 000 1 000 100 0.005 0.05 0.5 5 0.01 0.1 1 0.005 5 Concentration: EU/mL EU/ml EU/ml / 0010231 rfc 12 PyroGene Recombinant Factor C Endpoint Fluorescent Assay 12 tests 12 rfc6 / 2 2 (30 ml) 2 * 2012 6 FDA USP General Chapter 1225 Validation of Compendial Procedure 0.005 5 78,000 03-6264-066003-6264-0663 03-6264-0620 341

C 170 Detection step common to all BET assays Signal Amplification Steps Measured Characteristic Gel C lot Factor C Factor B Pro-clotting Enzyme Clotting Enzyme Coagulogen Coagulin Clot Formation visual observation / Development Timeline Current Kinetic Turbidimetric Endpoint Chromogenic Kinetic Chromogenic rfc Factor C Factor C Factor C Factor C Factor B Factor B Factor B Fluorogenic Substrate Pro-clotting Enzyme Pro-clotting Enzyme Pro-clotting Enzyme excitation @ 380 nm Clotting Enzyme Clotting Enzyme Clotting Enzyme Fluorescence @ 440 nm Difference from previous methods Coagulogen Chromogenic substrate Chromogenic substrate Coagulin Difference from previous methods rfc LAL C LAL Activity of 0.05 µg/ml LRM in EU/ml 2.00 1.50 0,10 Fluorescence (RFU) 100,000 10,000 1,000 Yellow Color Yellow Color Turbidity Measurement @340 nm Color Measurement @405 410 nm Color Measurement @405 nm Light Measurement @440 nm 0.05 Glucan Chromogenic rfc Glucan + Blocker LAL rfc LAL rfc 100 10 0.01 0.10 1.00 10.00 Concentration (EU/ml) Lot HL061M Lot HL076W Lot HL08K Lot HL100W Lot HL131C Lot JL017E Lot JL027A Lot JL043E rfc 8 log net 0.01 10 EU/mL 342 03-6264-066003-6264-0663 03-6264-0620

LAL PYROGENT LAL 60(+) ( ) PYROGENT 37 60 ( 2 ) 180 LAL CSE PYROGENT Plus CSE PYROGENT 2 PYROGENT 250 25 10 75 mm CSE EU/ml 0010165 N14-03J N14-06J 0.06 EU/ml 25 PYROGENT Plus Gel Clot LAL Assay (without endotoxin), single test vials 03 0.03 EU/ml 250 CSE PYROGENT Plus Gel Clot LAL Assay 0.03 (without CSE) 250 tests 0.06 EU/ml 250 CSE PYROGENT Plus Gel Clot LAL Assay 0.06 (without CSE) 250 tests 25 25 0.06 25,000 250 50 / 5 0.03 68,000 250 50 / 5 0.06 68,000 / CSE EU/ml 0010168 0.06 EU/ml 64 PYROGENT Plus Gel Clot LAL Assay 0.06 (with CSE) 64 tests 64 16 / 4 CSE 1 0.06 35,000 0010170 03 0.03 EU/ml 200 PYROGENT Plus Gel Clot LAL Assay 0.03 (with CSE) 200 tests 200 50 / 4 CSE 1 0.03 68,000 0010232 0.06 EU/ml 200 PYROGENT Plus Gel Clot LAL Assay 0.06 (with CSE) 200 tests 200 50 / 4 CSE 1 0.06 68,000 03-6264-066003-6264-0663 03-6264-0620 343

ELx808 QCL -5000 LAL 6 ELx808 / 55 50 UV ELx808 340 00 nm 340 405 450 40 630 nm 400 00 nm/0.000 4.000 Abs 340 400 nm/0.000 3.000 Abs 4 C 50 C WinKQCL 16 15.5 8.75 40.6 cm 3.4 cm 22.2 cm 35 15. kg 25-315S ELx808 ELx808 Reader 80,000 344 03-6264-066003-6264-0663 03-6264-0620

FLx800 rfc FLx800 rfc 380 nm 440 nm FLx800 WinKQCL FLx800 300 370 nm 4 C 50 C WinKQCL 16 15 40.6 cm 38.1 cm 22. cm 30 13.6 kg / 25-344 FLx800 FLx800 Reader 1,80,000 03-6264-066003-6264-0663 03-6264-0620 345

PyroTec PyroTec 6 6 PyroTec / PyroTec PyroTec Liquid handling system 346 03-6264-066003-6264-0663 03-6264-0620

WinKQCL Kinetic-QCL WinKQCL WinKQCL 521 CFR Part 11 WinKQCL 25-501 WinKQCL 5 CD * 500,000 WinKQCL 5 Software Package 25-502 WinKQCL 5 WinKQCL 5 Workgroup License 100,000 25-504 WinKQCL 5 WinKQCL 5 Qualification Manual IQ/OQ/PQ 280,000 25-505 WinKQCL 5 WinKQCL 5 Validation Package CD 500,000 25-33S IQ/OQ System Qualification Service IQ OQ 135,000 / 03-6264-066003-6264-0663 03-6264-0620 347

E.Coli O113 H10 USPRSE 10,000 EU/ E700 USP Reference Endotoxin Standard USP Reference Endotoxin Standard 1 4,000 CSE / N186 Control Standard Endotoxin for PYROGENT Gel Clot LAL Assays CSE 10 ng / 5 25,000 0013783 USP 0012568 USP 1 1000 EU-10,000 EU E.coli O55 B5 0013783 USP 1,250,000 EU/ Endotoxin 1,250,000 EU/ 5 0012568 USP 1,000 10,000 EU/vial Endotoxin Challenge Vials 1,000 10,000 EU/ 25 348 03-6264-066003-6264-0663 03-6264-0620

0010234 PYEOAPERSE Dispersing Agent 5 ml 5 32,000 0010167 S50-641 S50-642 β-g- β-g-blocker MgCl2 MgCl2 10 mm Solution Tris Buffer 50 mm 5 ml 5 28,000 10 mm 30 ml 1 50 mm 30 ml 1 5,000 5,000 / W50-640 LAL Reagent Water 30 ml 1 1,600 W50-100 LAL Reagent Water 100 ml 1 2,000 03-6264-066003-6264-0663 03-6264-0620 34

0010035 LAL Reagent Reservoirs 10 2,400 / 25-340 N201 N205 N207 0.0005 EU/well LAL Reagent Grade Multi-well Plates Pyrogen-free Test Tubes 10 75 mm Pyrogen-free Test Tubes 13 100 mm Pyrogen-free Test Tubes 50 45,000 50 10,000 50 7,000 30 8,000 350 03-6264-066003-6264-0663 03-6264-0620

80-507L 10 ml Sample Containers 10 ml 25 11,000 25-415 25-417 2-200 µl Eppendorf 2 200 µl Biopur Pipette Tips 50-1,000 µl Eppendorf 50 1000 µl Biopur Pipette Tips 6 / 5 6 / 5 18,000 20,000 / 03-6264-066003-6264-0663 03-6264-0620 351

Notes / 352 03-6264-066003-6264-0663 03-6264-0620