Shelf Life Prediction Of Medical Gloves

Shelf Life Prediction Of Medical Gloves Presented for the ASTM WG Committee for Medical Glove Expiration Dating Guidance By Uday Karmarkar Akron Rubber Development Laboratory, Inc. ardl@akron.infi.net

Motivation Shelf Life Prediction of rubber Medical Products Clients demand for reliable prediction of part shelf life in the laboratory Lack of incorporation of aging effects and chemical degradation Assessment is often qualitative - based on quality tests which are very misleading Address the nonlinear aging effects (Current FDA/ASTM/ISO Taskgroups)

Importance New shelf life prediction criteria New material development Safety, security and liability Material changes due to market trends Can reduce the number of product tests Cost of unexpected failure is high

Major Issues for Shelf Life What is the Mechanism of Aging? How is Aging defined? Can the Activation Energy be defined so that the temperature dependence of the failure can be found? Are the aging mechanisms the same at different temperatures? Can an accelarated test be run in the laboratory? Are the mechanisms the same in the laboratory as in storage?

Goals Need a scientific methodology for quantitative life prediction of elastomers Shelf life prediction Establishing the effectiveness of the existing models

Challenges Establishing accelerated aging techniques Establishing the degradation process/mechanisms Developing measurement techniques Establishing a basic practical model Establishing accuracy and reliability Establishing a degradation mechanism or aging mode Developing a good methodology which covers all thin elastomeric materials

Natural Aging Environmental Factors Alkali/Acid Elastomer Products Electricity Energy Oil/Solvent Radiation Air Ozone Light Water Corrosive mist Dust salt water Wind Stress (Static & Dynamic) Mechanical Stress Microbial Environment Corrosion Heat Molecular Chemical Transitions Additives Other Structural Physical Chemical Mechanical Electrical Properties Life Predictions

Degradation Process/Mechanism Thermal Thermo-Oxidative Photo Photooxidative Ozone Random Chain Scission Depolymerization Crosslinking Mechanical Hydrolytic Chemical High Energy Radiation Side Group Elimination Substitution Plasticizer Loss Filler Bonding Change

Accelerated Aging The basic requirement for reliable accelerated aging is that the course of degradation is identical at the storage and test conditions Measure minimum two structural parameters at a given temperature, physical properties and chemical analysis (extraction, swelling and analysis by mass spectrophotometer) Failure mode evaluation by two different techniques Incorporating all the aging conditions similar to storage

Degradation Monitoring Tests Modulus - Tensile Test Ultimate Elongation - Tensile Test Tensile Strength - Tensile Test Tear Strength Strain Energy ( Work to Break ) - Tensile Test FTIR (Field sample & Lab aged) Crosslink Density (Wet Chemistry) GC/MS Specific Gravity

Life Prediction Models Arrhenius Life Prediction Time Temperature Superposition ARDL P & K Method (Activation Energy successive averaging technique)

Time - Temperature Plot Decreasing Temperature 100 75 % Property Retention 50 25 0.1 1 10 100 1000 Log hours

Arrhenius Approach Life Limit Log Time Elevated Temperature Test Points Service Rating Temperature 1 / Temperature (Deg K) Increasing Temperature Typical Arrhenius Shelf Life Prediction Plot for Elastomeric Products

Arrhenius equation The Arrhenius Equation has the basic form where A = proportionality constant e = base for natural logarithms E = Activation Energy R = the gas constant T = Absolute Temperature k = A e -E / RT ln k = - E/ RT + ln A In General, for every 10 Deg C that temperature rises, the first order chemical reaction rate doubles

Arrhenius fit : Practical Issues An Arrhenius fit provides the worst case estimate of shelf life Arrhenius Approach prediction will be better with lower temperature test data Lower temperature data need more testing time The basic assumption is that the dominant mode of failure is identical at all temperatures and stress levels

Time - Temperature Superposition a t = exp { E a ( 1 / T (ref) -1/ T (age) } where Ea is the activation energy, R= gas constant ( 8.31432 J/K), Tref and Tage are the reference and aging temperatures respectively in Kelvin 100 50 75 80 70 60 Decreasing Temperature % Property Retention 50 25 0.1 1 10 100 1000 Log hours

Time - Temperature Superposition : Practical Issues Need to calculate Activation Energy Assume the activation energy as 84-117 KJ/mole High sensitivity on cutoff

ARDL P & K Method Activation energy (E) is averaged with a successive segment approach Predicted Data Points Ln (1 / seconds ) E8= E7+E6+E5+E4/4 E7=E6+E5+E4+E3/4 E6=E5+E4+E3+E2/4 E4 Calculated E3 Test Data Points E2 E5=E4+E3+E2+E1/4 E1 1 /Temperature (1 / K )

Successive Activation Energy Extrapolation : Practical Issues This method is sensitive to changes in activation energy Predictions are made depending upon the actual data available This method follows the change in Activation Energy

ARDL Aging Procedure Deg C 30 min 2 hrs 4 hrs 8 hrs 1 week 2 weeks 4 weeks 6 weeks 8 weeks 10 weeks 24 weeks 80 x x x x x x 70 x x x x x x x 60 x x x x x x x x x x 50 x x x x x x x x x Number of test specimens: 13 ( Tensile Test) Calculate coefficient of variation: CV = s/x (100%) Typical requirement: Maximum CV = 15% Correlation Coefficient (R 2 ) of Arrhenius plot Case I : R 2 > 0.97 use Arrhenius extrapolation Case II : R 2 < 0.97 use Successive Averaging technique

Natural Rubber Compounds

Natural rubber - Gloves Compound 1 Data at Data at Data at Data at Data at 0.00275 1/ T in K 0.0028303 1/ T in K 0.0029127 1/ T in K 0.00300012 1/ T in K 0.003093 1/ T in K 90 Deg Celsius 80 Deg Celsius 70 Deg Celsius 60 Deg Celsius 50 Deg Celsius Time Hrs % Property Time Hrs % Property Time Hrs % Property Time Hrs % Property Time Hrs % Property Retention Retention Retention Retention Retention 8 95 8 95 8 95 8 95 8 95 10 70 17 90 17 90 17 90 17 90 13 35 29 80 91 85 91 85 91 85 17 0 37 70 120 80 300 80 300 80 70 60 130 70 810 70 6000 60 91 30 190 55 1000 60 10000 45 100 10 370 25 1500 40 13000 30 600 5 2700 15 16000 15

NR Glove Compound 1: Raw Data 100 90 80 70 60 % Property Retention 50 40 30 20 10 0-10 90 Degrees Celsius 80 Degrees Celsius 70 Degrees Celsius 60 Degrees Celsius 50 Degrees Celsius 10 100 1000 10000 Tim e in hours

Time for aging to 70 % retention of Tensile Strength Temperature Deg C 50 60 70 80 90 Aging Time (hours) 1342 810 130 37 10

Shelf Life Prediction Curve : NR Compound 1 Average Slope Projection Technique Test D ata Average Slope Predicted Data Arrhenius Fit Arrhenius Fit Temperature in Degrees Celsius -21.0 20 25 30 40 50 60 70 80 90 ln (1 / seconds ) taken to reach 70 % Property Retention -20.5-20.0-19.5-19.0-18.5-18.0-17.5-17.0-16.5-16.0-15.5-15.0-14.5-14.0-13.5-13.0-12.5-12.0-11.5-11.0-10.5 s7 s6 s7 = (s3 + s4 + s5 + s6) / 4 s6 = (s2 + s3 + s4 + s5) / 4 s5 s5 = (s1 + s2 + s3 + s4) / 4 5 s4 s4 = y5-y4 / x5-x4 s3 = y4-y3 / x4-x3 4 s3 s2 = y3-y2 / x3-x2 3 s2 s1 = y2-y1 / x2-x1 2 s1 1 53227 109613 = 11.52 yrs 116828 = 6.07 yrs 24887 5671 1342 810 130 37 10 Time in hours ( to reach 70 %) -10.0 0.0035 0.0034 0.0033 0.0032 0.0031 0.0030 0.0029 0.0028 0.0027 1 / Temperature in Kelvin

Predicted Shelf Life: NR Glove Compound 1 Years Arrhenius Approach 11.52 ARDL P & K Method 6.07

NR: Glove Compound 2: Raw Data 110 Gloves - Shelf Life Prediction % Strength Retention 100 90 80 70 60 50 40 30 20 10 0 0.1 10 1000 100000 Time (hours) 90 Deg C 80 Deg C 70 Deg C 60 Deg C 50 Deg C

Time for Aging to 75 % Retention of Tensile Strength Temp DegC 90 80 70 60 50 Aging Time in Hrs 30 30 30 30 30

NR Glove Compound 2 : Arrhenius Plot Gloves - Arrhenius Plot 0.00 0.0025 0.0026 0.0027 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 0.0034-2.00 Ln ( 1/Seconds taken to reach 75 % of the origina strength) -4.00-6.00-8.00-10.00-12.00-14.00-16.00 y = -10105x + 15.65 R 2 = 0.9749 Test Data Linear (Test Data) -18.00-20.00 Temperature (1 / K)

Predicted Shelf Life : NR Glove Compound 2 Years Arrhenius Approach 3.31 ARDL P & K Method 1.15

NR Glove Compound 3 Data at Data at Data at 0.0028303 1/ T in K 0.002912734 1/ T in K 0.00300012 1/ T in K 80 Deg Celsius 70 Deg Celsius 60 Deg Celsius Time Hrs % Property Time Hrs % Property Time Hrs % Property Retention Retention Retention 72 75.2 168 75.8 336 81.2 168 60.2 336 71 504 82.4 336 20 504 57.4 672 85.3 504 1.7 672 43.8 840 65.4

NR: Compound 3: Raw Data 100 80 60 % Property Retention 40 20 0 60 Degrees Celcius 70 Degrees Celcius 80 Degrees Celcius 100 1000 Time in hours

Time for Aging to 75 % Retention of Tensile Strength Temperture 0 C 60 70 80 Aging Time in Hrs 708.035 266.6422 94.53996

Shelf Life Prediction Curve : NR Compound 3 Average Slope Projection Technique -21.0-20.5 T est D a ta Average Slope Predicted Data Arrhenius Fit Temperature in Degrees Celsius 20 25 30 40 50 60 70 80 A rrhenius Fit ln (1 / seconds ) taken to reach 75% Property Retention -20.0-19.5-19.0-18.5-18.0-17.5-17.0-16.5-16.0-15.5-15.0-14.5-14.0-13.5-13.0-12.5 s6 s6 = ( s4 + s5 + s6 ) / 3 s5 5 s5 = (s3 + s4 + s5) / 3 s4 4 s4 = (s2 + s3 + s4) / 3 s3 s3 = y4-y3 / x4-x3 s2 = y3-y2 / x3-x2 s1 = y2-y1 / x2-x1 3 s2 2 s1 1 80484.71 44831 = 5.1143 yrs 41550 = 4.7342 yrs 21871 6399.4 2055.57 708.035 266.64 94.54 Time in hours ( to reach 75 %) 0.0035 0.0034 0.0033 0.0032 0.0031 0.0030 0.0029 0.0028 1 / Temperature in Kelvin

Predicted Shelf Life : NR Compound 3 Shelf Life Technique Years Arrhenius Approach 5.11 ARDL P & K Method 4.73

Real time data Shelf life Estimate Technique for rubber Medical Gloves Wunan Huang, Maxxim Medical, Inc

110 Shelf Life Prediction - Wunan Huang, Maxxim Medical, Inc % Strength Retention 100 90 80 70 60 50 40 30 20 10 70 Deg C 50 Deg C 37 Deg C 0 1 100 10000 Time (hours)

Arrhenius Plot 0.00 0.0025 0.0026 0.0027 0.0028 0.0029 0.003 0.0031 0.0032 0.0033-2.00 Ln ( 1/Seconds taken to reach 75 % of the origina strength) -4.00-6.00-8.00-10.00-12.00-14.00-16.00-18.00 y = -9523.8x + 13.548 R 2 = 0.775 Test Dat a -20.00 Temperature (1 / K)

Shelf Life Prediction - Maxxim Medical Study Shelf Life Technique Years Arrhenius Approach 6.22 ARDL P & K Method 5.53 Real Time Study 5.6

Shelf Life Prediction - Maxxim Medical Study Shelf Life Prediction Technique 80 0 C 70 0 C Real time study ARDL P & K method Arrhenius Approach** * Segment Activation Energy, KJ/mole 70 0 C 60 0 C 60 0 C 50 0 C 50 0 C 40 0 C 40 0 C 30 0 C Shelf Life, years - - - - - 5.6 yrs* 110.68 114.43 78.36 101.16** 97.98** 5.53 yrs 101.7 101.7 101.7 101.7 101.7 6.22 yrs Note: * Real - time shelf life, ** Average of previous three segments, *** total slope based on regression analysis of the data from all the temperatures.

Latex Product Stability Medical Gloves Aging temperature ( 0 C) Time (w eeks) 80 1 70 3 60 10 50 24 This time - temperature matrix is established based on ARDL Client Shelf Life Prediction Studies.

Conclusion Successive Activation Energy extrapolation along with better obtained property retention data seems to be a good methodology/model for shelf life prediction of elastomers It is important to define aging modes/mechanisms Correlation between storage and lab data should be established based on a minimum of two testing techniques, preferably one physical test and one chemical test Each application should be studied separately for established shelf life prediction methodology

Conclusion (cont..) Quantitative shelf life prediction for materials will be a good guide for future specification development Sensitivity of the shelf life may be evaluated by modifying the threshold value by ± 10% Need more test data for accurate shelf life prediction for thermoplastic elastomers(preferably in 5 degree increments) Shelf life prediction as an engineering tool is in the infancy stage of development More applications related research is needed to establish the effectiveness of the package on shelf life prediction