Delivery portal. Flow moderator. Impermeable reservoir wall. Osmotic agent. Semipermeable membrane. Reservoir. 3 days. 1 day. 4 weeks. 1 week.

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Delivery portal Flow moderator Impermeable reservoir wall Osmotic agent Semipermeable membrane Reservoir 1 day 3 days 1 week 2 weeks 4 weeks 6 weeks 2

Dimensions, Components, and Materials of ALZET Osmotic Pumps ALZET Pump Model # 1003D 1007D 1002 1004 2001D 2001 2002 2004 2006 2ML1 2ML2 2ML4 Complete Osmotic Pump (pumps shown actual size) Length (cm) 1.5 3.0 5.1 Diameter (cm) 0.6 0.7 1.4 Weight (g) 0.4 1.1 5.1 Total Displaced Volume (ml) 0.5 1.0 6.5 Filling Tube Length (cm, tube only) 1.1 2.2 3.5 Gauge (tube) 27 27 25 O.D. (cm, tube) 0.04 0.04 0.05 I.D. (cm, tube) 0.02 0.02 0.03 Flow Moderator Length (cm) 1.3 2.4 4.6 Gauge (tube) 21 21 21 O.D. (cm, tube) 0.08 0.08 0.08 I.D. (cm, tube) 0.05 0.05 0.05 Weight (g) 0.05 0.2 0.9 Material (flange) Material (cap) Material (tube) Pump Body Materials Outer Membrane Drug Reservoir n/a Styrene Acrylonitrile Polyethylene Stainless Steel 304 Cellulose Ester Blend Thermoplastic Hydrocarbon Elastomer NOTE: The nominal performance is the target for all pumps manufactured. Individual lots of pumps may vary from this target within limits. The actual mean pumping rate and fill volume of a particular lot are listed, together with statistical parameters, on the instruction sheet included with each box. Nominal Performance of ALZET Osmotic Pumps ALZET Pump Model # 1003D 1007D 1002 1004 2001D 2001 2002 2004 2006 2ML1 2ML2 2ML4 Nominal Pumping Rate ( l /hr) Nominal Duration 1.0 0.5 0.25 0.11 8.0 1.0 0.5 0.25 0.15 10.0 5.0 2.5 3 days 7 days 14 days 4 weeks 1 day 1 week 2 weeks 4 weeks 6 weeks 1 week 2 weeks 4 weeks Nominal Reservoir Volume 100 l 200 l 2ML 3

Nominal Duration 0.5 Nominal Rate in vitro 0.1 0 2 4 6 8 Time (Days) Figure B: The pumping rate of the Model 2002 ALZET osmotic pump over time (n=20). 10 12 14 4 IN VITRO IN VIVO Start-up Time Nominal Duration 1.0 Nominal Rate 2 0.5 0 4 8 12 16 20 24 28 Time (Days) 0 4 12 24 48 Time (Hours) Figure A: The in vitro pumping rate of the Model 1003D ALZET osmotic pump over time (n=20). 72 Figure C: The pumping rate of the Model 2ML4 ALZET osmotic pump over time in vitro and in vivo in Sprague Dawley rats after subcutaneous implantation (n=105). www.alzet.com ALZET QuickTime ALZET 4

Estimated Minimum Animal Size For Implantation of ALZET Pumps ALZET Pump Model # Subcutaneous Mice Intraperitoneal Subcutaneous Rats Intraperitoneal 1003D 1007D 1002 10g 20g 10g 20g 1004 2001D 2001 2002 20g n/a 20g 150g 2004 2006 2ML1 2ML2 n/a n/a 150g 300g 2ML4 NOTE: The minimum animal size estimates are based on experience with male Sprague Dawley rats and Swiss Webster mice. When using the pumps with other types of rats and mice, or with animals other than rats and mice, these guidelines should be modified accordingly. (N/A = not applicable) Bird Cat Cattle Chinchilla Deer Dog Ferret Fish Frog Gerbil Goat Guinea pig Hamster Horse Iguana Kangaroo Mouse Mink Pig Primate Rabbit Rat Sheep Skunk Squirrel Toad Vole Please contact us to inquire about animal models not listed above. 5

Subcutaneous Intraperitoneal Intracavitary Articular Cavity Bladder Cerebral Ventricles Intestine Stomach Uterus Intravenous Intra-Arterial Intraluminal Local Tissue Microperfusion Arterial Wall Bone Brain Ear Eye Muscle Nerves Ovary Spinal Cord Spleen Testes Tumor 6

K = C x Q K = compound delivered per day, in g C = concentration of solution, in g/ l Q = release rate of pump, in l /hr 7

in vitro in vivo Models: 2001, 2002, 2004, 2001D, 1003D, 1007D, 1002, 1004, and 2006 (0.054T) Q = Q (0.135 e - (0.004 ) + 0.03) T 0 Models: 2ML1, 2ML2, and 2ML4 (0.051T) Q T = Q 0 (0.141 e - (0.007 ) + 0.12) Q T = the pumping rate at temperature T Q 0 = the specified pumping rate at 37 in l /hr T = temperature in degrees Celsius = osmolality of the solution outside the pump (atm) 1.3 Model 2001 Model 2ML1 13.0 1.2 12.0 1.1 11.0 Pumping Rate Model 2001 1.0 0.9 0.8 0.7 0.6 0.5 10.0 9.0 8.0 7.0 6.0 5.0 Pumping Rate Model 2ML1 0.4 0.3 0.2 0.15 0 10 20 30 40 Temperature ( ) 4.0 3.0 2.0 1.5 Mammalian Core Temperature The pumping rate of ALZET osmotic pumps varies in direct proportion to temperature. This graph shows the representative pumping rates for two pump models from 4 to over 40 in 0.9% saline. 8

Acids, with ph greater than 1.8 Bases, with ph less than 14 Cremophor EL, up to 25% in water Culture media (1% benzyl alcohol as bacteriostatic) -Cyclodextrins Dextrose, up to 5%, in water or NaCl N,N-Dimethyl formamide (DMF), up to 25% in water DMSO, up to 50% in water or polyethylene glycol 1-Methyl-2-Pyrrolidone, up to 12.5% in water Phosphate buffer Polyethylene glycol 300 or 400, neat or in water Propylene glycol, neat or in water Ringer's solution (with or without lactate) Saline, 0.9% (or other aqueous salt solution) Serum (rat, mouse, etc.) Solutol, up to 30% in water DMSO, up to 50% in ethanol ( Ethanol, up to 15% in water Glycerol 15% ) and water Triacetin, up to 5% in water Tween 80, up to 2% Water, distilled 9

100 l and 200 l p umps b efore a nd a fter the a ttachment o f c atheters. Model Explant Pumps By* 10 Request a Free Video CD Demonstrating ALZET Surgical Procedures: Subcutaneous Intragastric Intraperitoneal Intrathecal Intravenous Pump filling (via external jugular) Brain Infusion Kit assembly Intracerebral Lynch coil preparation 1003D 1007D 1002 1004 2001D 2001 2002 2004 2006 2ML1 2ML2 2ML4 Day 5 Day 10 Day 21 Day 42 Day 1.5 Day 10 Day 21 Day 42 Day 63 Day 10 Day 21 Day 42 *Data shown correspond to the nominal duration. Actual explant date should be calculated using the exact specifications for each lot of pumps.

Brain Infusion Cannula Material (tube) Gauge (tube) Dimensions (steel tube) Material (elbow stop, flange) Volume inside tube Height Adjustment Spacer Material Catheter Tubing Material Length Inside diameter Outside diameter Volume per 15 cm Brain Kits 1 & 2 Brain Kit 3 28 gauge ID = 0.18 mm OD = 0.36 mm 0.32 l Stainless steel Polycarbonate Polycarbonate Polyvinylchloride (medical grade) 15 cm (approx.) 0.69 mm (+/- 0.08) 1.14 mm (+/- 0.08) 56 1 (3.7 l /cm) 30 gauge ID = 0.16 mm OD = 0.31 mm 0.23 l ALZET Brain Infusion Kit 1 28 gauge 3-5 mm original cannula design ALZET Brain Infusion Kit 2 28 gauge 3-5 mm low profile cannula wide pedestal ALZET Brain Infusion Kit 3 30 gauge 1-3 mm low profile cannula wide pedestal 11

Visit www.alzet.com > Products > catheters for detailed specifications Description Item No. Length Outside Diameter Inside Diameter Volume Vinyl Tubing (10 per bag) 0007760 15 cm (6 in) 1.14 mm (0.045 in) 0.69 mm (0.027 in) 3.74 l /cm Item Number: 0008670 Comes as: 3 gram tube Polyethylene Tubing (10 per bag) 0007750 15 cm (6 in) 1.22 mm (0.048 in) 0.72 mm (0.030 in) 4.566 l /cm 12