Accelerated Age Testing - DDL

Accelerated Age TestingPresented by: Scott LevyDDL Packaging Engineer

Outline Introduction / What is Accelerated Aging?Scope of ASTM F1980Significance and UseUnderstanding Accelerated Theory & RationaleTolerances and PrecisionCautions Using Accelerated AgingThe Use of HumidityPost Aging GuidanceConclusionQuestionswww.testedandproven.com

IntroductionSimply stated Accelerated aging is an artificial procedurethat allows you to claim expiration dating ofmaterials by utilizing elevated temperatures.“Shelf Life refers to the period of time a sterilizedor disinfected item is safe to use.”“An Expiration Date is the termination of the shelflife.”

Introduction Standard Guide developed within ASTMCommittee F 2.60 on Medical Packaging Guide approved on May 10, 1999 First published document providingguidance on performing accelerated agingof medical device packages for establishingshelf life.

Introduction ASTM Standard was developed to provide aguidance for compliance to ANSI/AAMI/ISO11607-1:2006;Section 6.4.3Stability testing using accelerated agingprotocols, shall be regarded as sufficient evidencefor claimed expiry dates until data from real-timeaging studies are available.

Scope of ASTM F 1980 Provides information for developingaccelerated aging protocols. Information may be used to support shelflife and expiration date claims. Real time aging protocols are not addressedin this guide.

Significance and Use Package components and adhesives maybreakdown, become brittle, or lose bondingcapabilities over time. Real time aging is the most valid program. Real time aging is not practical.– Requires too much time to get to market

Significance and Use Conservative aging factors must be used iflittle information is known about thepackaging materials. (Q10 of 2) Use of accelerated aging protocols involvessome risk.

Accelerated Aging Theory Materials are subjected to an external stress. Techniques are based on the assumption that thechemical reactions involved in deterioration ofmaterials follow the Arrhenius reaction ratefunction.(Q10). Determining Q10 requires modeling the kinetics ofmaterials and is very complex and difficult. So a conservative Q10 is used in medical devicepackage validation.

Accelerated Aging RationalEuropean Community Council Directive93/42/EEC, ANNEX 1, “Essential Requirements”states “The label must bear the following particulars.where appropriate, an indication of the date bywhich the device should be used, in safety,expressed as the year and month.”

Accelerated Aging RationalISO 11607:2006, section 6.4; Paraphrased “For medical devices with a defined shelf-life, themanufacturer shall have documented evidence that theperformance of the packaging is not adversely affectedby storage under specified conditions for a period not lessthan the shelf-life of the medical device.This shall be demonstrated by real time aging testing.”Accelerated aging testing may be undertaken inaddition to real time aging under conditions of increasedseverity.”

ISO 11607:2006, section 6.4;further states “If accelerated aging tests are performed, adocumented rationale for the accelerated agingconditions and test duration chosen shall beestablished. Accelerated aging may beregarded as sufficient evidence for the claimedshelf life on the introduction of new products.This does not preclude the requirement toperform real-time aging tests.”

DOCUMENTED RATIONALE The ASTM F 1980, “Standard Guide forAccelerated Aging of Sterile Medical DevicePackages” provides the documentedrationale for performing accelerated agingto establish shelf life. This ASTM ‘Standard’ is recognized by theFDA as a consensus standard.

Most package Shelf Life validation protocolsare based on the ASTM Guide and Accelerated Aging of Packaging: Considerations,Suggestions, and Use in Expiration Date VerificationReich, Sharpe, AndersonMDDI, March 1988Accelerated Aging test parameters are based on theQ10 thermodynamic temperature coefficient(Arrhenius Theory)

Arrhenius Reaction Rate Theorystates.“a rise in temperature of 10oC will roughly double therate of a chemical reaction”So.AAR (Accelerated Aging Rate) Q10 ((Te - Ta)/10)Where.Ta Ambient TemperatureTe Elevated TemperatureQ10 Reaction Rate 2And.AATD (Accelerated Aging Time Duration) Desired Real TimeAAR

FOR EXAMPLEIf the desired real time aging or expiration date of themedical device is three years, and the testtemperature is chosen to be 55oC, Q10 is 2; the AATD isdetermined as follows.AAR (Q10 ) 2 ((55-22)/10) 9.85AATD 365 days/9.85 37.06 daysAATD 37.06 days/yearTotal duration:1 Year 37.06 Days3 Year 37.06 x 3 111.18 Days (Rounded Up: 112 Days)

Accelerated Aging Equivalency MatrixACCELERATED AGING EQUIVALENCYTABLEbased on Q10 2ambient Temp. 22C1 YEAR SHELFLIFEDEGREES CDEGREES 5551315.3601403.8651492.7701581.9751671.4

The Use of HumiditySection: 6.5A humidity factor to calculate the accelerated aging(AAT) is not applicable for accelerated agingProtocols. Unrealistic or extreme temperature andConditions may be of interest in overall sterilebarrier system performance. However, this must beevaluated in a separate study and is not related toaccelerated aging.

The Use of Humidity Cont.Section: X3.1 Aging damage for many materials may beexacerbated in the presence of high humidity. Delimitation of water based laminates orcoexstrusions. The relative humidity that is chosen should beequivalent to the moisture content or theabsolute humidity extrapolated from real timeaging conditions that will be utilized.

The Use of Humidity Cont.Table X3.1:

The Use of Humidity Cont.So what does DDL Recommend? DDL recommends the use of 20% RH forAccelerated Aging Protocols. Aging is a factor of time and temperature. Keeping the RH levels low is important to notoverstress the packaging materials to a failurethat is not observed in the real world. Further climatic stressing (Humidity) should takeplace in performance studies and is more realisticto what transpires in the real world.

Temperature/Humidity Chambers forAccelerated Aging Studies

TOLERANCES AND PRECISIONTemperature and Humidity Tolerances Temp /- 2 C Humidity /-5 % Since this is a conservative estimate of shelflife, out of tolerance conditions on the lowend for an extended period of time may becorrected with additional test time.

TOLERANCES AND PRECISION Out of tolerance conditions on the high end ofthe required test temperature for an extendedperiod of time may jeopardize the shelf lifestudy due to uncharacteristic damage topackaging materials and/or to actual product.

TOLERANCES AND PRECISION Since humidity is not essential to the agingtheory, out of tolerance humidity conditionsdo not invalidate the shelf life study.

TOLERANCES AND PRECISION When conducting an accelerated agingprogram for establishing product and packageshelf life or expiration dating claims, it mustbe recognized that the data obtained from thestudy is based on conditions that simulate theeffects of aging on the materials.

TOLERANCES AND PRECISION The resulting creation of an ‘expiration date’or shelf life represents a conservative estimateof shelf life and is tentative until the results ofreal time aging studies are completed on theproduct or product/package combination.

TOLERANCES AND PRECISION Since the results of the study produce a conservativeestimate of the actual shelf life of the materials,tolerances for the temperature and humidity are onlyprovided to ensure that the chamber operates withina satisfactory range. Accelerated aging is a cumulativeeffect. The average temperature and humidity wouldbe given a higher emphasis because of the thermal lagin bringing product and chamber into equilibrium,when a short term excursion occurs. Therefore, out oftolerance excursions for less than 6 hours in durationfor either temperature or humidity are acceptable anddo not adversely affect the estimate for shelf life.

TOLERANCES AND PRECISION Out of tolerance excursions may be caused byopening doors for sample transfer; insertingmoist samples into a dry environment causingspikes in humidity; proximity of monitoringdevice to temperature and/or humidity sourceinlets.

Cautions in Using AcceleratedAging Theory

Cautions in Using AcceleratedAging Theory Accelerated aging is truly a gift by the FDAand EU to allow MDM’s to release productsto market faster. MDM’s push the limits on a daily basis bytrying to increase the temperature abovethe cautioned 60 C to save time. This theory is based upon homogeneousmaterials.

Cautions in Using AcceleratedAging Theory Reaction Rates may not be a linear functionat temperatures above 60oC. Errors in the theory increase as temperatureincreases. Multi component materials may react atdifferent rates.

Cautions in Using AcceleratedAging Theory Elevating the temperature of packagingmaterials could result in a mode of failurenever observed in real life. Melting plastic, warping, crystallization The glass-transition temperature of thematerials could be reached, drasticallyaltering the characteristics of the package.

Cautions in Using AcceleratedAging Theory Ideally, in order for the Q10 based acceleratedaging program to be utilized, the individualreactions rates of all package componentsshould be identified. Accelerated aging studies must be conductedin parallel with real time, ambient packagingstudies

Post Aging Testing GuidanceAging is a conditioning test and byitself does not evaluate the efficacy ofthe package system. Therefore Packages must be evaluated for physicalproperties and integrity. Tests should challenge the most criticalproperty.

Post Aging Testing Guidance Strength tests methods include: Peel Strength Burst strengthSeal Strength Testing per ASTM F88

Post Aging Testing Guidance Integrity test methods include; bubble leak,dye penetrationDye Penetration Testingper ASTM F 1929Bubble Leak Testingper ASTM F 2096

Conclusions Accelerated aging theory is complex evenfor homogeneous materials. These theories are all the medical deviceindustry has to use for validatingcompliance with international andnational requirements. Results of these tests will be aconservative estimate of shelf life.

Conclusions Provide the necessary time tocomplete an aging study. Understand ALL the materials you areutilizing (Product & Package) prior topicking an aging temperature toutilize. If you choose to push the agingtemperature limits a solid justificationabove 60 will be needed.

Questions?Please don’t hesitate to contact Scott with any 26 ext. 115

Seal Strength Testing per ASTM F88 . Post Aging Testing Guidance Integrity test methods include; bubble leak, dye penetration Dye Penetration Testing per ASTM F 1929 Bubble Leak Testing per ASTM F 2096 . Conclusions Accelerated