NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
`Contact ASTM International (www.astm.org) for the latest information
`
`Designation: F 1980 – 02
`
`Standard Guide for
`Accelerated Aging of Sterile Medical Device Packages1
`
`This standard is issued under the fixed designation F 1980; the number immediately following the designation indicates the year of
`original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
`superscript epsilon (e) indicates an editorial change since the last revision or reapproval.
`
`1. Scope
`1.1 This guide provides information for developing accel-
`erated aging protocols to rapidly determine the effects, if any,
`due to the passage of time and environmental effects on the
`sterile integrity of packages and the physical properties of their
`component packaging materials.
`1.2 Information obtained using this guide may be used to
`support expiration date claims for medical device packages.
`1.3 The accelerated aging guideline addresses the primary
`medical package in whole and does not address the package
`and product interaction or compatibility that may be required
`for new product development. Package and product compat-
`ibility and interactions should be addressed as a material
`analysis process before package design.
`1.4 Real-time aging protocols are not addressed in this
`guide; however, it is essential that real-time aging studies be
`performed to confirm the accelerated aging test results using
`the same methods of evaluation.
`1.5 Methods used for package process validation, which
`include the machine process, the effects of the sterilization
`process, distribution, handling, and shipping events, are be-
`yond the scope of this guide.
`1.6 This standard does not purport to address all of the
`safety concerns,
`if any, associated with its use. It
`is the
`responsibility of the user of this standard to establish appro-
`priate safety and health practices and determine the applica-
`bility of regulatory limitations prior to use.
`
`2. Referenced Documents
`2.1 ASTM Standards: 2
`D 3078 Test Method for Determination of Leaks in Flexible
`Packaging by Bubble Emission
`
`1 This guide is under the jurisdiction of ASTM Committee F02 on Flexible
`Barrier Materials and is the direct responsibility of Subcommittee F02.50 on
`Package Design and Development.
`Current edition approved Jan. 10, 2002. Published March 2002. Originally
`published as F 1980 – 99. Last previous edition F 1980 – 99e1.
`2 For referenced ASTM standards, visit the ASTM website, www.astm.org, or
`contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
`Standards volume information, refer to the standard’s Document Summary page on
`the ASTM website.
`
`D 4169 Practice for Performance Testing of Shipping Con-
`tainers and Systems
`D 4332 Practice for Conditioning Containers, Packages, or
`Packaging Components for Testing
`E 337 Test Method for Measuring Humidity with a Psy-
`chrometer (the Measurement of Wet- and Dry-Bulb Tem-
`peratures)
`F 88 Test Method for Seal Strength of Flexible Barrier
`Materials
`F 1140 Test Methods for Internal Pressurization Failure
`Resistance of Unrestrained Packages for Medical Applica-
`tions
`F 1327 Terminology Relating to Barrier Materials for Medi-
`cal Packaging
`F 1585 Guide for Integrity Testing of Porous Barrier Medi-
`cal Packages
`F 1608 Test Method for Microbial Ranking of Porous Pack-
`aging Materials (Exposure Chamber Method)
`F 1929 Test Method for Detecting Seal Leaks in Porous
`Medical Packaging by Dye Penetration
`2.2 AAMI Standards:
`ANSI/AAMI/ISO 11607, Packaging for Terminally Steril-
`ized Medical Devices3
`AAMI TIR 17-1997, Radiation Sterilization—Material
`Qualification3
`
`3. Terminology
`3.1 Definitions—For general definitions of packaging for
`medical devices see ANSI/AAMI/ISO 11607. For terminology
`related to barrier materials for medical packaging see Termi-
`nology F 1327.
`3.2 Definitions of Terms Specific to This Standard:
`3.2.1 accelerated aging (AA), n—storage of samples at an
`elevated temperature (TAA) in order to simulate real time aging
`in a reduced amount of time.
`3.2.2 accelerated aging factor (AAF), n—an estimated or
`calculated ratio of the time to achieve the same level of
`physical property change as a package stored at real time (RT)
`conditions.
`
`3 Available from the American National Standards Institute, 25 W. 43rd St., 4th
`Floor, New York, NY 10036.
`
`Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.
`
`1
`
`Regeneron Exhibit 1230.001
`Regeneron v. Novartis
`IPR2021-00816
`
`(cid:39)(cid:82)(cid:90)(cid:81)(cid:79)(cid:82)(cid:68)(cid:71)(cid:72)(cid:71)(cid:18)(cid:51)(cid:85)(cid:76)(cid:81)(cid:87)(cid:72)(cid:71)(cid:18)(cid:36)(cid:70)(cid:70)(cid:72)(cid:86)(cid:86)(cid:72)(cid:71)(cid:3)(cid:69)(cid:92)(cid:3)(cid:88)(cid:86)(cid:72)(cid:85)(cid:29)(cid:3)(cid:37)(cid:85)(cid:72)(cid:81)(cid:71)(cid:68)(cid:15)(cid:3)(cid:51)(cid:68)(cid:81)(cid:70)(cid:75)(cid:68)(cid:80)(cid:3)(cid:95)(cid:3)(cid:39)(cid:68)(cid:87)(cid:72)(cid:29)(cid:3)(cid:55)(cid:88)(cid:72)(cid:3)(cid:48)(cid:68)(cid:85)(cid:3)(cid:21)(cid:28)(cid:3)(cid:20)(cid:26)(cid:29)(cid:24)(cid:23)(cid:29)(cid:22)(cid:23)(cid:3)(cid:21)(cid:19)(cid:21)(cid:21)
`
`

`

`F 1980 – 02
`
`3.2.3 accelerated aging temperature (TAA), n—the elevated
`temperature at which the aging study is conducted, and it may
`be based on the estimated storage temperature, estimated usage
`temperature, or both.
`3.2.4 accelerated aging time (AAT), n—the length of time
`the accelerated aging is conducted.
`3.2.5 ambient temperature (TRT), n—storage temperature
`for real-time aging (RT) samples that represents storage con-
`ditions.
`3.2.6 package shelf life, n—the amount of real time that a
`package can be expected to remain in storage at ambient
`conditions, or under specified conditions of storage, and
`maintain its critical performance properties.
`3.2.7 real-time aging (RT), n—storage time of samples at
`ambient conditions.
`3.2.8 real-time equivalent (RTE), n—amount of real-time
`aging to which given accelerated aging conditions are esti-
`mated to be equivalent.
`3.2.9 zero time (t0), n—the beginning of an aging study.
`3.3 Symbols:
`
`Q10 = an aging factor for 10°C increase or decrease in
`temperature.
`= temperature at which a material melts.
`= glass transition temperature.
`= alpha temperature; heat distortion temperature.
`
`Tm
`Tg
`Ta
`
`4. Significance and Use
`4.1 The loss of package integrity may occur as a result of
`physical properties of the materials and adhesive or cohesive
`bonds degrading over time and by subsequent dynamic events
`during shipping and handling.
`4.2 The ANSI/AAMI/ISO 11607 states that, “the manufac-
`turer shall demonstrate that, under the rigors of distribution,
`storage, handling, and aging, the integrity of the final package
`is maintained at least for the claimed shelf-life of the medical
`device under storage conditions specified by the manufacturer,
`as long as the package is undamaged or unopened.”
`4.3 Real
`time aging programs provide the best data to
`ensure that package materials and package integrity do not
`degrade over time. However, due to market conditions in
`which products become obsolete in a short time, and the need
`to get new products to market in the shortest possible time, real
`time aging studies do not meet this objective. Accelerated
`aging studies provide an alternative means. To ensure that
`accelerated aging studies do truly represent real time effects,
`real
`time aging studies must be conducted in parallel
`to
`accelerated studies. Real time studies must be carried out to the
`claimed shelf life of the product.
`4.4 Conservative accelerated aging factors (AAFs) must be
`used if little is known about
`the package material being
`evaluated. More aggressive AAFs may be used with docu-
`mented evidence to show a correlation between real time and
`accelerated aging.
`
`NOTE 1—Determining AAFs are beyond the scope of this guide.
`
`5. Apparatus
`5.1 Room (or Cabinet) of such size that sample containers
`or packages may be individually exposed to circulating air at
`the temperature and relative humidity chosen.
`5.1.1 Control Apparatus, capable of maintaining the room at
`the required atmospheric conditions within the tolerance limits.
`5.2 Hygrometer—The instrument used to indicate the rela-
`tive humidity should be accurate to 62 % relative humidity. A
`psychrometer may be used either for direct measurement of
`relative humidity or for checking the hygrometer (see Test
`Method E 337).
`5.3 Thermometer—Any temperature-measuring device may
`be used provided it can accurately indicate the temperature to
`within 0.1°C or 0.2°F. The dry-bulb thermometer of the
`psychrometer may be used either for direct measurement or for
`checking the temperature-indicating device.
`
`6. Accelerated Aging Theory
`6.1 Accelerated aging of materials refers to the accelerated
`variation of their properties over time, the properties of interest
`being those related to safety and function of the material or
`package.
`6.2 In an aging study, the material or package is subjected to
`an external stress, which is more severe, or more frequently
`applied than the normal environmental stress, for a relatively
`short period of time.
`6.3 Accelerated aging techniques are based on the assump-
`tion that the chemical reactions involved in the deterioration of
`materials follow the Arrhenius reaction rate function. This
`function states that a 10°C increase or decrease in temperature
`of a homogeneous process results in approximately, a two
`times or 1⁄2-time change in the rate of a chemical reaction
`(Q10)4.
`6.4 Determining the Q10 involves testing products at various
`temperatures and defining the differences in reaction rate for a
`10° change in temperature. Modeling the kinetics of material
`deterioration is complex and difficult and is beyond the scope
`of this guide.5
`
`7. Accelerated Aging Plan
`7.1 Characterization of Materials—AA theory and its ap-
`plication are directly related to packaging material composi-
`tion. Some areas for consideration are:
`7.1.1 Composition,
`7.1.2 Morphology (glassy, amorphous, semi-crystalline,
`highly crystalline, % crystallinity, etc.),
`7.1.3 Thermal transitions (Tm, Tg, Ta),
`7.1.4 Additives, processing agents, catalysts,
`residual solvents, and fillers.
`7.2 Accelerated Aging Plan-Design Guidelines:
`7.2.1 Temperature boundaries, based on the characterization
`of the device and package materials, must be considered in
`
`lubricants,
`
`4 Hemmerich, Karl J., “General Aging Theory and Simplified Protocol for
`Accelerated Aging of Medical Devices,” Medical Plastics and Biomaterials,
`July/August 1998, pp. 16–23.
`5 Nelson, Wayne, “Accelerated Testing Statistical Models, Test Plans, and Data
`Analyses,” John Wiley and Sons, New York, 1999.
`
`2
`
`Regeneron Exhibit 1230.002
`Regeneron v. Novartis
`IPR2021-00816
`
`(cid:39)(cid:82)(cid:90)(cid:81)(cid:79)(cid:82)(cid:68)(cid:71)(cid:72)(cid:71)(cid:18)(cid:51)(cid:85)(cid:76)(cid:81)(cid:87)(cid:72)(cid:71)(cid:18)(cid:36)(cid:70)(cid:70)(cid:72)(cid:86)(cid:86)(cid:72)(cid:71)(cid:3)(cid:69)(cid:92)(cid:3)(cid:88)(cid:86)(cid:72)(cid:85)(cid:29)(cid:3)(cid:37)(cid:85)(cid:72)(cid:81)(cid:71)(cid:68)(cid:15)(cid:3)(cid:51)(cid:68)(cid:81)(cid:70)(cid:75)(cid:68)(cid:80)(cid:3)(cid:95)(cid:3)(cid:39)(cid:68)(cid:87)(cid:72)(cid:29)(cid:3)(cid:55)(cid:88)(cid:72)(cid:3)(cid:48)(cid:68)(cid:85)(cid:3)(cid:21)(cid:28)(cid:3)(cid:20)(cid:26)(cid:29)(cid:24)(cid:23)(cid:29)(cid:22)(cid:23)(cid:3)(cid:21)(cid:19)(cid:21)(cid:21)
`
`

`

`F 1980 – 02
`
`order to ensure that initial, conservative aging factors are
`applied appropriately. The temperatures used should be based
`on the characterization of the packaging materials and the
`intended storage conditions. Material characterization and
`composition are factors in establishing the accelerated aging
`temperature boundaries. Temperature selection should be lim-
`ited to prevent any physical transition of material.
`7.2.2 Room or Ambient Temperature (TRT)—Select a tem-
`perature that represents the actual product storage and use
`conditions.
`
`NOTE 2—This temperature is typically between 20–25°C. A tempera-
`ture of 25°C is considered a conservative approach.
`7.2.3 Accelerated Aging Temperature (TAA)—Considering
`the characterization of the materials under investigation, select
`a temperature for the accelerated aging testing. The higher the
`accelerated temperature, the greater the AAF and, thus, the
`shorter the accelerated aging time. Care must be taken not to
`elevate aging temperatures solely for the shortest possible
`accelerated aging time. Excessively high temperatures may
`have an effect on the material that may never occur during real
`time or at room temperature (see Appendix X1). Guidelines for
`selecting an aging temperature are as follows:
`7.2.3.1 TAA should be below any material transitions or
`below where the package distorts. Consider the thermal tran-
`sitions of the materials under investigation, for example, the
`choice of TAA should be at least 10°C less than Tg. (For more
`information on this topic, see AAMI TIR 17-1997.)
`7.2.3.2 Keep TAA at or below 60°C unless a higher tempera-
`ture has been demonstrated to be appropriate. Temperatures
`higher than 60°C are not recommended due to the higher
`probability in many polymeric systems to experience nonlinear
`changes, such as percent crystallinity, formation of free radi-
`cals, and peroxide degradation. (For more information on this
`topic, see AAMI TIR 17-1997.)
`
`NOTE 3—If packages containing liquid or other volatile components are
`tested, lower temperatures may be required for safety reasons.
`
`7.2.3.3 When elevated temperature aging is not feasible due
`to material characteristics, then real-time aging is the only
`option.
`7.3 Accelerated Aging Factor (AAF) Determination:
`7.3.1 Using the Arrhenius equation with Q10 equal to 2 is a
`common and conservative means of calculating an aging
`factor.
`
`NOTE 4—A more aggressive reaction rate coefficient, for example,
`Q10= 2.2 to 2.5, may be used if the system under investigation is
`sufficiently well characterized in the literature. The level and nature of
`damage must be similar to that reported in the literature to ensure that the
`reaction rate coefficient and accelerated aging temperature are maintained
`within appropriate boundaries. This is the responsibility of the manufac-
`turer. For more information on this topic see AAMI TIR-17-1997.
`
`7.3.2 An accelerated aging factor (AAF) estimate is calcu-
`lated by the following equation:
`
`AAF [ Q10
`
`@~TAA – TRT!/10]
`
`(1)
`
`where:
`TAA [ accelerated aging temperature (°C), and
`TRT [ ambient temperature (°C).
`
`7.3.3 The accelerated aging time (AAT) needed to establish
`equivalence to real time aging is determined by dividing the
`desired (or required) shelf life by the AAF.
`(2)
`Accelerated Aging Time ~AAT! [ Desired ~RT!/AAF
`See Appendix X1 for a graphical representation of the time
`versus temperature.
`7.3.4 When little information is known about the package
`under investigation, the guidance above is provided for select-
`ing and verifying an appropriately conservative aging factor for
`the specific scenario. Risk to the manufacturer may be large
`since the method may predict an unduly short shelf-life;
`however, consideration must be given to maximizing patient
`safety since the necessary information to obtain a more
`accurate and aggressive shelf-life prediction is not readily
`available.
`7.4 Accelerated Aging Protocol Steps:
`7.4.1 Select the Q10 value.
`7.4.2 Define the desired shelf life of the package, such as,
`marketing needs, product needs, etc.
`7.4.3 Define aging test time intervals, including time zero.
`7.4.4 Define test conditions, room temperature (TRT), and
`accelerated aging temperature (TAA).
`7.4.5 Calculate the test duration using the Q10, TRT, and TAA.
`7.4.6 Define package material properties, seal strength and
`integrity tests, sample sizes, and acceptance criteria.
`7.4.7 Age samples at TAA. In parallel, age samples at
`real-life aging conditions (TRT).
`7.4.8 Evaluate the package performance after accelerated
`aging relative to the initial package requirements, for example,
`package seal strength, package integrity.
`7.4.9 Evaluate package, or package performance, or both,
`after real time aging relative to the initial package require-
`ments. The estimated AAF method is a simple and conserva-
`tive technique for evaluating the long-term performance of a
`package; however, like all accelerated aging techniques, it
`must be confirmed by real time aging data.
`7.5 See the example package shelf-life test plan (Appendix
`X2).
`
`8. Post-Aging Testing Guidance
`8.1 Packages and materials that have been subjected to
`aging, that is, accelerated and real time, must be evaluated for
`physical properties and integrity.
`8.2 Tests selected should challenge the material or package
`functionality that is most critical or most likely to fail due to
`the stresses resulting from aging. Guide F 1585 may be used as
`a testing guide for porous barrier medical packaging.
`8.3 Some of the physical strength properties to be consid-
`ered for selection are flexure, puncture, tensile and elongation,
`tear, impact resistance, abrasion resistance, yellowness index,
`microbial barrier (Test Method F 1608), seal strength (Test
`Method F 88), and burst strength (Test Methods F 1140).
`8.4 Packages may be subjected to whole package integrity
`testing by using validated physical, that is, trace gas detection,
`dye leak (Test Method F 1929), bubble leak (Test Method
`D 3078) or microbial methods (microbial challenge of whole
`packages). These methods must include documentation show-
`ing that the test method has been validated.
`
`3
`
`Regeneron Exhibit 1230.003
`Regeneron v. Novartis
`IPR2021-00816
`
`(cid:39)(cid:82)(cid:90)(cid:81)(cid:79)(cid:82)(cid:68)(cid:71)(cid:72)(cid:71)(cid:18)(cid:51)(cid:85)(cid:76)(cid:81)(cid:87)(cid:72)(cid:71)(cid:18)(cid:36)(cid:70)(cid:70)(cid:72)(cid:86)(cid:86)(cid:72)(cid:71)(cid:3)(cid:69)(cid:92)(cid:3)(cid:88)(cid:86)(cid:72)(cid:85)(cid:29)(cid:3)(cid:37)(cid:85)(cid:72)(cid:81)(cid:71)(cid:68)(cid:15)(cid:3)(cid:51)(cid:68)(cid:81)(cid:70)(cid:75)(cid:68)(cid:80)(cid:3)(cid:95)(cid:3)(cid:39)(cid:68)(cid:87)(cid:72)(cid:29)(cid:3)(cid:55)(cid:88)(cid:72)(cid:3)(cid:48)(cid:68)(cid:85)(cid:3)(cid:21)(cid:28)(cid:3)(cid:20)(cid:26)(cid:29)(cid:24)(cid:23)(cid:29)(cid:22)(cid:23)(cid:3)(cid:21)(cid:19)(cid:21)(cid:21)
`
`

`

`F 1980 – 02
`
`8.5 Acceptance criteria must be established prior to any
`package shelf-life testing. Zero time performance data may be
`used as a comparison to final package performance data at the
`end of the shelf life test.
`
`9. Documentation
`9.1 Accelerated Aging:
`9.1.1 A written test protocol specifying the accelerated
`aging conditions (test temperature, humidity, cycle, ambient
`temperature), time frame, sample sizes, package description,
`time intervals of sampling packages, and specific tests at each
`time interval must be developed prior to testing.
`9.1.2 Document the temperature of the chamber used and
`the calibrated instruments used for measuring and monitoring
`the aging conditions.
`
`9.1.3 Document the test standard references and methods
`used for package evaluation.
`9.1.4 List the equipment used for physical and microbial
`testing including the calibration dates.
`9.1.5 Document the post aging test results including, any
`statistical methods used to determine whether the package
`meets the performance specification criteria.
`
`10. Keywords
`10.1 accelerated aging; Arrhenius reaction rate; Q10;
`shelf-life
`
`APPENDIXES
`
`(Nonmandatory Information)
`
`X1. ACCELERATED AGING OF POLYMERS
`
`X1.1 Accelerated aging (Fig. X1.1) equivalent to one year
`of room-temperature aging when the package is heat-aged at a
`
`selected temperature (°C).
`
`4
`
`Regeneron Exhibit 1230.004
`Regeneron v. Novartis
`IPR2021-00816
`
`(cid:39)(cid:82)(cid:90)(cid:81)(cid:79)(cid:82)(cid:68)(cid:71)(cid:72)(cid:71)(cid:18)(cid:51)(cid:85)(cid:76)(cid:81)(cid:87)(cid:72)(cid:71)(cid:18)(cid:36)(cid:70)(cid:70)(cid:72)(cid:86)(cid:86)(cid:72)(cid:71)(cid:3)(cid:69)(cid:92)(cid:3)(cid:88)(cid:86)(cid:72)(cid:85)(cid:29)(cid:3)(cid:37)(cid:85)(cid:72)(cid:81)(cid:71)(cid:68)(cid:15)(cid:3)(cid:51)(cid:68)(cid:81)(cid:70)(cid:75)(cid:68)(cid:80)(cid:3)(cid:95)(cid:3)(cid:39)(cid:68)(cid:87)(cid:72)(cid:29)(cid:3)(cid:55)(cid:88)(cid:72)(cid:3)(cid:48)(cid:68)(cid:85)(cid:3)(cid:21)(cid:28)(cid:3)(cid:20)(cid:26)(cid:29)(cid:24)(cid:23)(cid:29)(cid:22)(cid:23)(cid:3)(cid:21)(cid:19)(cid:21)(cid:21)
`
`

`

`F 1980 – 02
`
`FIG. X1.1 Accelerated Aging of Polymers1
`
`X2. EXAMPLE PACKAGE SHELF-LIFE TEST PLAN
`
`X2.1 Select a conservative AAF estimate, for example, Q10
`= 2. (See Fig. X2.1.)
`
`X2.2 Define aging time points corresponding to the desired
`shelf life, for example, two points, such as 2-year and 3-year.
`
`NOTE X2.1—Trending often is helpful when characterizing the aging
`effects on material and package properties. The number of accelerated
`aged time points, minimally, is one. The one mandatory time point is at the
`time equivalent to the desired shelf-life (desired shelf-life divided by
`aging factor); however, the practice of using only one accelerated time
`point leaves the risk of failure without prior warning from an earlier
`accelerated aged time point. At
`least
`three time points should be
`considered when trending.
`
`X2.3 Build test samples in accordance with a validated
`production process.
`
`NOTE X2.2—Packages used for zero-time, sterilization, and accelerated
`aging may be produced without actual or simulated product.
`
`X2.4 Sterilize packages using validated sterilization pro-
`cess. The sterilization process may affect the stability of the
`materials or package. Materials and packages should be ex-
`posed to the maximum process conditions, or number of cycles
`intended to be used prior to the aging study, or both.
`
`X2.5 Condition the samples according to Practice D 4332,
`if required; perform distribution simulation according to Prac-
`tice D 4169, if appropriate. Packages used for this test must
`contain actual product.
`
`NOTE X2.3—Package performance testing normally is performed as a
`part of the aging protocol to determine the long-term effects of distribu-
`tion, handling, and storage. Whether performed before aging or after aging
`will depend on whether the study is to simulate storage on the hospital
`shelf or on the manufacturer’s shelf and then shipped. There may be
`instances, however, where this may not be necessary. If known package
`failure or performance limits, such as seal strength, puncture, or impact
`resistance, etc., have been documented adequately and met for the specific
`intended product, then physical testing data should be sufficient.
`
`Initiate real-time and accelerated aging. Use the
`X2.6
`defined accelerated aging temperature for the appropriate
`period of time. The time duration for samples to be placed in
`the elevated temperature oven can be calculated from Eq 1 and
`2 in 7.3.2 and 7.3.3, where AAF is the accelerated aging factor
`and AAT is the accelerated aging time.
`For example, where Q10 = 2; ambient temperature = 23°C;
`test temperature = 55°C;
`AAF = 2.0(55−23)/10;
`AAF = 2.03.2 = 9.19;
`AAT = 365 days/9.19; and
`AAT [ 39.7 days [ 12 months (real-time equivalent).
`
`NOTE X2.4—The effects of humidity may need to be considered in
`conjunction with temperature and incorporated into a test cycle of high
`and low humidity duration’s. An aging cycle may be designed to account
`for the effects of humidity.
`
`X2.7 Evaluate package performance after accelerated aging
`relative to the package requirements.
`
`5
`
`Regeneron Exhibit 1230.005
`Regeneron v. Novartis
`IPR2021-00816
`
`(cid:39)(cid:82)(cid:90)(cid:81)(cid:79)(cid:82)(cid:68)(cid:71)(cid:72)(cid:71)(cid:18)(cid:51)(cid:85)(cid:76)(cid:81)(cid:87)(cid:72)(cid:71)(cid:18)(cid:36)(cid:70)(cid:70)(cid:72)(cid:86)(cid:86)(cid:72)(cid:71)(cid:3)(cid:69)(cid:92)(cid:3)(cid:88)(cid:86)(cid:72)(cid:85)(cid:29)(cid:3)(cid:37)(cid:85)(cid:72)(cid:81)(cid:71)(cid:68)(cid:15)(cid:3)(cid:51)(cid:68)(cid:81)(cid:70)(cid:75)(cid:68)(cid:80)(cid:3)(cid:95)(cid:3)(cid:39)(cid:68)(cid:87)(cid:72)(cid:29)(cid:3)(cid:55)(cid:88)(cid:72)(cid:3)(cid:48)(cid:68)(cid:85)(cid:3)(cid:21)(cid:28)(cid:3)(cid:20)(cid:26)(cid:29)(cid:24)(cid:23)(cid:29)(cid:22)(cid:23)(cid:3)(cid:21)(cid:19)(cid:21)(cid:21)
`
`

`

`F 1980 – 02
`
`FIG. X2.1 Package Shelf-Life Test Plan
`
`X2.7.1 If the accelerated aging results meet the acceptance
`criteria then the product’s shelf-life conditionally is validated
`depending upon the results of the real-time aging study.
`the
`X2.7.2 If the accelerated aging results fail
`to meet
`acceptance criteria then either investigate the production pro-
`cess, redesign the failed medical device or package, attempt to
`validate a shorter shelf-life, or wait for real time aging results.
`The shelf-life is validated if real
`time aging results are
`acceptable. In this scenario, the accelerated aging program is
`more rigorous than reality.
`
`X2.8 Evaluate package performance after real-time aging
`
`relative to the package requirements.
`
`X2.8.1 If the real-time aging results meet the acceptance
`criteria, then the package’s shelf-life is validated.
`X2.8.2 If the real-time aging results fail to meet the accep-
`tance criteria, the shelf-life must be reduced to the longest shelf
`life for which real time testing has been successful. If product
`has been released to the market at risk based on the accelerated
`aging data, a careful review must be performed and docu-
`mented, and the appropriate action taken.
`
`6
`
`Regeneron Exhibit 1230.006
`Regeneron v. Novartis
`IPR2021-00816
`
`(cid:39)(cid:82)(cid:90)(cid:81)(cid:79)(cid:82)(cid:68)(cid:71)(cid:72)(cid:71)(cid:18)(cid:51)(cid:85)(cid:76)(cid:81)(cid:87)(cid:72)(cid:71)(cid:18)(cid:36)(cid:70)(cid:70)(cid:72)(cid:86)(cid:86)(cid:72)(cid:71)(cid:3)(cid:69)(cid:92)(cid:3)(cid:88)(cid:86)(cid:72)(cid:85)(cid:29)(cid:3)(cid:37)(cid:85)(cid:72)(cid:81)(cid:71)(cid:68)(cid:15)(cid:3)(cid:51)(cid:68)(cid:81)(cid:70)(cid:75)(cid:68)(cid:80)(cid:3)(cid:95)(cid:3)(cid:39)(cid:68)(cid:87)(cid:72)(cid:29)(cid:3)(cid:55)(cid:88)(cid:72)(cid:3)(cid:48)(cid:68)(cid:85)(cid:3)(cid:21)(cid:28)(cid:3)(cid:20)(cid:26)(cid:29)(cid:24)(cid:23)(cid:29)(cid:22)(cid:23)(cid:3)(cid:21)(cid:19)(cid:21)(cid:21)
`
`

`

`F 1980 – 02
`
`ASTM International takes no position respecting the validity of any patent rights asserted in connection with any item mentioned
`in this standard. Users of this standard are expressly advised that determination of the validity of any such patent rights, and the risk
`of infringement of such rights, are entirely their own responsibility.
`
`This standard is subject to revision at any time by the responsible technical committee and must be reviewed every five years and
`if not revised, either reapproved or withdrawn. Your comments are invited either for revision of this standard or for additional standards
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`
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`address or at 610-832-9585 (phone), 610-832-9555 (fax), or service@astm.org (e-mail); or
`through the ASTM website
`(www.astm.org).
`
`7
`
`Regeneron Exhibit 1230.007
`Regeneron v. Novartis
`IPR2021-00816
`
`(cid:39)(cid:82)(cid:90)(cid:81)(cid:79)(cid:82)(cid:68)(cid:71)(cid:72)(cid:71)(cid:18)(cid:51)(cid:85)(cid:76)(cid:81)(cid:87)(cid:72)(cid:71)(cid:18)(cid:36)(cid:70)(cid:70)(cid:72)(cid:86)(cid:86)(cid:72)(cid:71)(cid:3)(cid:69)(cid:92)(cid:3)(cid:88)(cid:86)(cid:72)(cid:85)(cid:29)(cid:3)(cid:37)(cid:85)(cid:72)(cid:81)(cid:71)(cid:68)(cid:15)(cid:3)(cid:51)(cid:68)(cid:81)(cid:70)(cid:75)(cid:68)(cid:80)(cid:3)(cid:95)(cid:3)(cid:39)(cid:68)(cid:87)(cid:72)(cid:29)(cid:3)(cid:55)(cid:88)(cid:72)(cid:3)(cid:48)(cid:68)(cid:85)(cid:3)(cid:21)(cid:28)(cid:3)(cid:20)(cid:26)(cid:29)(cid:24)(cid:23)(cid:29)(cid:22)(cid:23)(cid:3)(cid:21)(cid:19)(cid:21)(cid:21)
`
`