# US 12,216,736 B2 · Reducing probability of glass breakage in drug delivery devices > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,216,736 B2 - Document ID: US12216736B2 - Status: Granted - Kind: B2 - Application number: 17/520,961 - Filed: 2021-11-08 - Published: 2022-06-30 - Granted: 2025-02-04 - Earliest claimed: 2016-03-15 - Assignees: Amgen Inc. - Applicants: Amgen Inc. - Inventors: Sean Fitzgibbon; Christopher R. Folk; Julian Jazayeri - Web page: https://patentgrep.com/patent/US12216736B2 ## CPC - G06F 17/18: for evaluating statistical data {, e.g. average values, frequency distributions, probability functions, regression analysis (forecasting specially adapted for a specific administrative, business or logistic context G06Q10/04)} - A61M 5/2033: {Spring-loaded one-shot injectors with or without automatic needle insertion (multishot dosing syringes A61M5/31525, needle insertion only A61M5/3287)} - A61M 5/315: Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod {or piston}; Appliances on the rod for facilitating dosing {; Dosing mechanisms} - G06F 30/17: Mechanical parametric or variational design - G06F 30/20: Design optimisation, verification or simulation (optimisation, verification or simulation of circuit designs G06F30/30) - G16H 20/17: delivered via infusion or injection - A61M 5/206: {with automatic needle insertion} - A61M 5/3202: {Devices for protection of the needle before use, e.g. caps (A61M5/50 takes precedence; protectors for sharps A61B50/3001)} - A61M 2205/3327: Measuring - A61M 2205/3331: Pressure; Flow - A61M 2205/3375: Acoustical, e.g. ultrasonic, measuring means - A61M 2205/50: with microprocessors or computers - A61M 2205/70: with testing or calibration facilities - A61M 2207/00: Methods of manufacture, assembly or production - G06F 17/13: Differential equations (using digital differential analysers G06F7/64) - G06F 2111/08: Probabilistic or stochastic CAD - G06F 2111/10: Numerical modelling - G06F 2113/08: Fluids - G06F: ELECTRIC DIGITAL DATA PROCESSING (computer systems based on specific computational models G06N) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA ## Abstract A method for determining predicted failure rates of drug injection devices includes receiving a set of parameters specifying physical properties of a syringe, a liquid drug, and a drug injection device configured to deliver the liquid drug to a patient via the syringe, the drug injection device including a mechanism that drives a plunger rod toward a plunger of the syringe encased in a syringe carrier. The method also includes receiving failure rate data specifying a measured rate of failure of the drug injection device in response to various peak pressures within the syringe, applying the set of parameters to a kinematic model of the drug injection device to determine a predicted peak pressure within the syringe, determining a probability of failure of the drug injection device using the failure rate data and predicted peak pressure, and providing an indication of the determined probability of failure to an output device. ## Claims ### Claim 1 A non-transitory computer-readable medium storing thereon instructions that, when executed on one or more processors, implement a method for determining predicted failure rates of drug injection devices, the method comprising: receiving a set of parameters that specify physical properties of (i) a syringe, (ii) a liquid drug, and (iii) a drug injection device configured to deliver the liquid drug to a patient via the syringe, wherein the drug injection device includes a mechanism configured to drive a plunger rod toward a plunger of the syringe encased in a syringe carrier; receiving failure rate data that specifies a measured rate of failure of the drug injection device in response to various peak pressures within the syringe; applying the received set of parameters to a kinematic model of the drug injection device to determine a predicted peak pressure within the syringe, including determining the predicted peak pressure as a function of impact velocity of the liquid drug, and including using the kinematic model to model interactions between at least the mechanism, the plunger rod, the plunger, and the syringe carrier, wherein using the kinematic model includes (A) modeling the mechanism as a linear spring with an equilibrium length, and/or (B) modeling (i) a pre-impact stage at which the plunger rod has not come in contact with the plunger, and (ii) a first impact stage at which the plunger rod comes in contact with the plunger; determining a probability of failure of the drug injection device using (i) the received failure rate data and (ii) the predicted peak pressure; and providing an indication of the determined probability of failure to an output device. ### Claim 2 (depends on 1) The computer-readable medium of claim 1, wherein the kinematic model is a two-dimensional kinematic model. ### Claim 3 (depends on 1) The computer-readable medium of claim 1, wherein the implemented method further comprises modeling a fluid column in the syringe as an acoustic medium. ### Claim 4 (depends on 1) The computer-readable medium of claim 1, wherein the implemented method further comprises modeling a fluid column in the syringe using a Korteweg equation. ### Claim 5 (depends on 1) The computer-readable medium of claim 1, wherein using the kinematic model includes modeling (i) the pre-impact stage at which the plunger rod has not come in contact with the plunger, (ii) the first impact stage at which the plunger rod comes in contact with the plunger, and (iii) a second impact stage at which the syringe carrier comes in contact with a front shell. ### Claim 6 (depends on 1) The computer-readable medium of claim 1, wherein receiving the set of parameters to the kinematic model includes receiving geometric parameters related to at least one of the syringe or the drug injection device, including at least one of: (i) plunger depth, (ii) plunger rod wall thickness, (iii) plunger rod activation length, (iv) syringe barrel diameter, (v) syringe wall thickness, (vi) fluid volume, (vii) syringe carrier activation length, (viii) plunger rod depth, (ix) length of the guide rod, (x) length of guide rod base, (xi) length of needle insertion, (xii) needle length, (xiii) needle, or (xiv) un-sprung length of spring. ### Claim 7 (depends on 1) The computer-readable medium of claim 1, wherein receiving the set of parameters to the kinematic model includes receiving parameters indicative of masses of components, including at least one of: (i) mass of syringe carrier, (ii) mass of pre-filled syringe with drug, (iii) mass of plunger, (iv) mass of rod, or (iv) mass of spring. ### Claim 8 (depends on 1) The computer-readable medium of claim 1, wherein receiving the set of parameters to the kinematic model includes receiving at least one of the following (a) through (e): (a) a parameter indicative of plunger elasticity, (b) a parameter indicative of fluid sound speed, (c) a parameter indicative of viscosity of the drug, (d) a spring constant, and/or (e) experimental data indicative of a plurality of test runs of an actual drug injector device that shares at several physical properties with the drug injection device being modeled, and deriving one or more of (i) syringe driver friction, (ii) internal plunger damping, and (iii) plunger-syringe friction. ### Claim 9 (depends on 1) The computer-readable medium of claim 1, wherein determining the probability of failure of the drug injection device includes applying a two-term Weibull distribution function. ### Claim 10 A method for manufacturing drug injection devices, the method comprising: receiving, by one or more processors, a fixed set of parameters that specify physical properties of a syringe and a liquid drug; determining a set of parameters that specify physical properties of a drug injection device configured to deliver the liquid drug to a patient via the syringe, wherein the drug injection device includes a mechanism configured to drive a plunger rod toward a plunger of the syringe encased in a syringe carrier, wherein determining the set of parameters includes: (i) generating, by the one or more processors, a candidate set of parameters for the drug injection device, (ii) applying, by the one or more processors, the fixed set of parameters and the candidate set of parameters to a kinematic model of the drug injection device to determine a predicted peak pressure within the syringe, including determining the predicted peak pressure as a function of impact velocity of the liquid drug, and including using the kinematic model to model interactions between at least the mechanism, the plunger rod, the plunger, and the syringe carrier, wherein using the kinematic model includes (A) modeling the mechanism as a linear spring with an equilibrium length, and/or (B) modeling (i) a pre-impact stage at which the plunger rod has not come in contact with the plunger, and (ii) a first impact stage at which the plunger rod comes in contact with the plunger, (iii) determining, by the one or more processors, a probability of failure of the drug injection device using the determined predicted peak pressure, (iv) if the probability of failure is above a threshold value, repeating the steps (i)-(iii) with a modified candidate set of parameters, and (v) selecting the candidate set of parameters if the probability of failure is not above the threshold value; and manufacturing the drug injection device using the determined set of parameters. ### Claim 11 (depends on 10) The method of claim 10, wherein the kinematic model is a two-dimensional kinematic model. ### Claim 12 (depends on 10) The method of claim 10, further comprising modeling a fluid column in the syringe as an acoustic media. ### Claim 13 (depends on 10) The method of claim 10, further comprising modeling a fluid column in the syringe using a Korteweg equation. ### Claim 14 (depends on 10) The method of claim 10, wherein using the kinematic model includes modeling (i) the pre-impact stage at which the plunger rod has not come in contact with the plunger, (ii) the first impact stage at which the plunger rod comes in contact with the plunger, and (iii) a second impact stage at which the syringe carrier comes in contact with a front shell. ### Claim 15 (depends on 10) The method of claim 10, wherein receiving the set of parameters that specify the physical properties of the drug injection device includes receiving at least one of the following (a) through (g): (a) geometric parameters for one or several components of the drug injection device, (b) parameters indicative of masses of components of the drug injection device (c) a parameter indicative of plunger elasticity, (d) a parameter indicative of fluid sound speed, (e) a parameter indicative of viscosity of the drug, (f) a spring constant, and/or (g) experimental data indicative of a plurality of test runs of an actual drug injector device that shares at several physical properties with the drug injection device being modeled, and deriving one or more of (i) syringe driver friction, (ii) internal plunger damping, and (iii) plunger-syringe friction. ### Claim 16 A drug injection device configured to deliver a liquid drug to a patient via a syringe, the drug injection device prepared by a process comprising: receiving a fixed set of parameters that specify physical properties of a syringe and a liquid drug; determining a set of parameters that specify physical properties of a drug injection device configured to deliver the liquid drug to a patient via the syringe, wherein the drug injection device includes a mechanism configured to drive a plunger rod toward a plunger of the syringe encased in a syringe carrier, and wherein determining the set of parameters includes: (i) generating a candidate set of parameters for the drug injection device; (ii) applying the fixed set of parameters and the candidate set of parameters to a kinematic model of the drug injection device to determine a predicted peak pressure within the syringe, including determining the predicted peak pressure as a function of impact velocity of the liquid drug, and including using the kinematic model to model interactions between at least the mechanism, the plunger rod, the plunger, and the syringe carrier, wherein using the kinematic model includes (A) modeling the mechanism as a linear spring with an equilibrium length, and/or (B) modeling (i) a pre-impact stage at which the plunger rod has not come in contact with the plunger, and (ii) a first impact stage at which the plunger rod comes in contact with the plunger, (iii) determining a probability of failure of the drug injection device using the determined predicted peak pressure, (iv) if the probability of failure is above a threshold value, repeating the steps (i)-(iii) with a modified candidate set of parameters, and (v) selecting the candidate set of parameters if the probability of failure is not above the threshold value; and using the determined set of parameters to manufacture the drug injection device. ### Claim 17 (depends on 16) The drug injection device of claim 16, wherein the kinematic model is a two-dimensional kinematic model. ### Claim 18 (depends on 16) The drug injection device of claim 16, wherein the process further comprises modeling a fluid column in the syringe as an acoustic media. ### Claim 19 (depends on 16) The drug injection device of claim 16, wherein the process further comprises modeling a fluid column in the syringe using a Korteweg equation. ### Claim 20 (depends on 16) The drug injection device of claim 16, wherein the process comprises modeling (i) the pre-impact stage at which the plunger rod has not come in contact with the plunger, (ii) the first impact stage at which the plunger rod comes in contact with the plunger, and (iii) a second impact stage at which the syringe carrier comes in contact with a front shell.