1、Designation: F3169 16Standard Test Method forLeak Detection in Blister Packaging by Vacuum DeflectionMethod by Laser Measurement1This standard is issued under the fixed designation F3169; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revis
2、ion, the year of last revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon () indicates an editorial change since the last revision or reapproval.1. Scope1.1 Test PackagesThis test method can be applied tonon-porous blister packs sealed with flexible films su
3、ch asthose used in pharmaceutical packaging. Such blister packstypically consist of thermoformed polymer or cold formedaluminum trays that contain a number of individual blisterpockets into which tablets or capsules are placed. The trays arethen sealed with a polymer, paper-backed or foil-based flex
4、iblelaminate lidding material.1.2 Leaks DetectedThis test method detects leaks inblister packs by measuring the deflection of the blister packsurface in response to an applied vacuum. This deflection of theblister pack surface results from the difference in pressurebetween the gas inside the blister
5、 pack and the applied vacuum.Air loss from within a blister pocket as a result of a leak willalter this pressure differential causing a measureable variationin blister pocket deflection. This test method requires that theblister packs are held in appropriate tooling inside a suitabletest chamber.1.3
6、 Test ResultsTest results are reported qualitatively(pass/fail). Appropriate acceptance criteria for deflection,height, and collapse values are established by comparingnon-leaking packs with those containing defects of a knownsize. Suitably sized defects in the laminate, tray material, andseal can b
7、e detected using this test method. The sensitivity ofthis test method depends upon a range of factors includingblister pocket headspace, blister pocket size, lidding materialtype, lidding material thickness, lidding material tension,printing, surface texture, test conditions, and the values se-lecte
8、d for the pass/fail acceptance criteria. The ability of thetest to detect 15 m, 50 m, and catastrophic sized holes in fourblister pack designs was demonstrated in a study.1.4 The values stated in SI units are to be regarded asstandard and no other units of measurement are included in thistest method
9、.1.5 This standard does not purport to address all of thesafety concerns, if any, associated with its use. It is theresponsibility 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
10、Documents2.1 ASTM Standards:2D996 Terminology of Packaging and Distribution Environ-mentsF17 Terminology Relating to Flexible Barrier Packaging3. Terminology3.1 For definitions used in this test method, see Terminolo-gies D996 and F17.3.2 Definitions of Terms Specific to This Standard:3.2.1 blister
11、pack, nforming material, encapsulatedproduct, and sealed lidding material.3.2.2 blister pocket, nsealed cavity in the forming mate-rial that contains product.3.2.3 collapse, ndifference in height of the blister pocketprofile in one plane before and after the reduced vacuum hasbeen applied.3.2.4 defl
12、ection, ndifference in height of the blister pocketprofile in one plane before and after the initial vacuum has beenapplied.3.2.5 height, ndifference in height of the blister pocketprofile in one plane after initial vacuum when comparedagainst blister pack surface height.3.2.6 profile, nsurface of t
13、he lidding material measured atregular intervals across the blister pocket.4. Summary of Test Method4.1 The test blister packs are located in the test chamber inappropriate tooling to prevent them from moving undervacuum. The chamber is then sealed and the profile of every1This test method is under
14、the jurisdiction of ASTM Committee F02 on PrimaryBarrier Packaging and is the direct responsibility of Subcommittee F02.40 onPackage Integrity.Current edition approved Dec. 1, 2016. Published January 2017. DOI: 10.1520/F3169-162For referenced ASTM standards, visit the ASTM website, www.astm.org, orc
15、ontact ASTM Customer Service at serviceastm.org. For Annual Book of ASTMStandards volume information, refer to the standards Document Summary page onthe ASTM website.Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United StatesThis international st
16、andard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for theDevelopment of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.1bli
17、ster pocket is measured using an appropriate measurementdevice such as a laser and actuator (see Fig. 1).4.2 A vacuum is then applied to the test chamber and eachblister pocket measured again. Sealed blister pockets can beidentified by the change in measurement between the first andsecond profiles.
18、This is known as deflection and is caused bythe pressure difference between the air inside the blister pocketand the air in the chamber caused by the application of vacuum(see Fig. 2).4.3 The deflection of a blister pocket with a gross hole willbe minimal as the pressure difference between the air i
19、nsideand outside of the blister pocket will equalize through the hole.4.4 The sensitivity of the test can be increased by holdingthe test samples under vacuum for a period of time and thenreducing the vacuum level. After reducing the vacuum, thesurface profile of the blister pockets can be measured
20、again andcompared with the profiles recorded after the initial vacuumwas applied. Reducing the vacuum level causes blister pocketswith small holes to have a collapse measurement greater thanblister pockets with no defects. This is due to air leaking fromany small defects (see Fig. 3).4.5 The sensiti
21、vity of the test is a function of the testparameters chosen, namely vacuum levels, hold time, and thepass/fail criteria selected. Blister pack design including head-space and blister pocket size, lidding material, lidding materialthickness, lidding material tension, printing, and surface tex-ture ca
22、n affect test sensitivity. The vacuum levels used aretypically in the range of 30 - 60 KPa and are chosen based onsetup tests conducted using good blister packs and thosecontaining defects of known size. The required vacuum leveldepends upon the blister pack design and materials. Forexample, detecti
23、ng sub-15 m defects in small blister pocketssealed with a stiff lidding material typically requires vacuumlevels towards the higher end of the standard range. Thevacuum level is then reduced and the packs are rescanned aftera holding period (typically 10 - 45 s) at this reduced vacuum.The test param
24、eters, including the pass/fail criteria, are chosenby comparing the deflection and collapse values of good blisterpacks and those containing defects of the required size. Suchdefects can be produced by using a wire, by laser drilling, or byapplying self-adhesive predrilled holes.4.6 Where blister po
25、ckets appear pre-swollen the flat sealedsurface of the blister pack is used to project a datum line acrossthe blister pocket from which a change in height under vacuumcan be observed. If this height value is small or negative it canbe understood that the blister pocket has a gross hole, as thebliste
26、r pocket has not deflected due to vacuum or positivepressure before testing (see Fig. 4).4.7 Any blister pocket that falls outside the acceptancecriteria for deflection, collapse,orheight is recorded as a fail.The ability of the test to detect 15 and 50 m sized laser drilledholes was verified using
27、four blister pack designs. This methodwas also used to find large catastrophic defects demonstratedwitha5mmslit in the lidding material.4.8 Background noise may occur due to movement of theblister pack under vacuum. Such noise can be minimized byselection of an appropriate measurement device, proper
28、 reten-tion of the blister pack, and careful selection of pressures usedfor testing.5. Significance and Use5.1 Leaks in blister packs may affect product quality andsuch defects can arise from imperfections in the packagingmaterial or bond between the sealed surfaces.5.2 This method of leak testing i
29、s a useful tool as it allowsnon-destructive and non-subjective leak testing of blisterpacks. It allows the operator to evaluate how different pack-aging materials and packaging machine conditions affect theintegrity of the packaging. It can also provide indication ofunwanted changes in the packaging
30、 conditions.5.3 This type of testing is typically used in pharmaceuticalpackaging production, during stability trials and for packageresearch and development operations because of its non-destructive nature, cleanliness, and speed.FIG. 1 ProfileF3169 1626. Apparatus6.1 The leak testing instrumentati
31、on consists of a vacuumchamber and measurement device (see Fig. 5).6.2 Test ChamberThe test chamber maintains the blisterpacks under vacuum, typically at levels between 30 - 60 kPaduring the test cycle. It locates the lower and upper tooling,FIG. 2 DeflectionFIG. 3 CollapseFIG. 4 HeightF3169 163allo
32、wing the measurement device to accurately pinpoint theblister packs. The test chamber shall be of sufficient size tohouse the measurement device/devices and allow them to movebetween all the blister pocket positions.6.3 Measurement DeviceThe measurement device movesover each pack scanning the surfac
33、e of every pocket. Theprofile of the lidding material is measured with reference to afixed datum. A typical measurement device is a red semicon-ductor laser with a resolution of 0.05 m in the z-plane at areference distance of 30 6 5 mm.6.4 Lower ToolThe lower tool accurately locates theblister packs
34、 for testing.6.5 Upper ToolThe upper tool sandwiches the blisterpacks and ensures that they do not move under vacuum.6.6 Vacuum SourceA suitable vacuum source is selectedbased on a target vacuum level and the time required to reachthe vacuum target.6.7 Vacuum MeasurementA suitable sensor is selected
35、 tomonitor the vacuum level within the test chamber.7. Hazards7.1 As the test chamber is closed it may present a pinchhazard.7.2 Standard precautions should be followed if using anylaser-based measurement device.8. Preparation of Apparatus8.1 The test apparatus shall be started and made ready inacco
36、rdance with the manufacturers specifications. Assumingthe vacuum is being provided by an air driven vacuum pump,utilities required for instrument operation include electricalpower and a dry, non-lubricated air supply in accordance withthe manufacturers specifications. Other vacuum sources maybe used
37、.8.2 A suitable set of tooling specific to the blister packsformat is also required to ensure that the test samples areretained during the application of the vacuum within thechamber.9. Calibration and Standardization9.1 Vacuum CalibrationThe machine vacuum measure-ment is calibrated using an extern
38、al vacuum source andcalibrated vacuum meter.9.2 Position and HeightThe profile measurement systemis calibrated using a test tool that contains slip gauges of knownheight. The measurement tracking is also calibrated using a testtool with machined features at known x-y positions.10. Procedure10.1 Turn
39、 on instrumentation and check supply pressure.10.2 Select and install appropriate tooling into test chamber.10.3 Place test packaging into lower tooling for testing.10.4 Select appropriate vacuum levels and holding times forleak testing the samples.10.5 Scan blister pack surface, measuring the initi
40、al blisterpocket profile.10.6 Apply initial vacuum level and hold for the chosen settime and rescan the blister pockets.10.7 Calculate deflection (difference in profile before andafter vacuum) for each blister pocket. Any blister pockets withdeflection values below the pass criteria are recorded as
41、a fail.10.8 Calculate height (difference in datum from sealedsurface minus profile after vacuum) for each blister pocket.Any blister pockets with height values below the pass criteriaare recorded as a fail.10.9 If the test method calls for a second reduced vacuumlevel, the pressure should be increas
42、ed to this level and theblister packs rescanned after a set time period.10.10 Collapse values (difference in profile between initialand reduced vacuum levels) should be calculated for eachblister pocket. Any blister pockets with collapse levels abovethe threshold criteria are recorded as fails.10.11
43、 Record the results, setting aside any failed blisterpacks for further evaluation where appropriate.10.12 If a failed blister pack contains product that maycontaminate the test chamber or system during the leak test,perform steps to eliminate contaminant from the system.FIG. 5 Leak Testing Instrumen
44、tationF3169 16411. Report11.1 The test report should include the following informa-tion:11.1.1 A statement that the tests were conducted in accor-dance with this standard, noting any deviations from thespecified test method.11.1.2 The machine type, serial number, date of calibration,and date of test
45、ing.11.1.3 Blister pack information, including materialinformation, blister pocket size, and free head space (ifknown).11.1.4 The specific test procedure used, including thevacuum level and hold times.11.1.5 The acceptance criteria for height, deflection, andcollapse.11.1.6 Pass/fail results for eac
46、h blister pocket tested and acopy of any software generated data sheets and/or reportsproduced during the testing.12. Precision and BiasNOTE 1Refer to Table 1 for a summary of the pharmaceutical blisterpackages used to generate the precision and bias data presented. All of thetest equipment used in
47、the studies was manufactured by Sepha Ltd.NOTE 2The test results are expressed in qualitative terms (pass/fail)and the precision and bias data is presented in terms of percentages ofblister pockets meeting the test criteria.12.1 A study was conducted on three sites in order toascertain the precision
48、 and bias of this test method. The resultsare shown in Table 2. The ability of the method to detect both15 and 50 m sized holes was evaluated using the tablet andcapsule pack designs as described in Table 1. These tests wereconducted at three locations, each using a separate instrument.For each of t
49、he two pack designs, 25 blister packs were laserdrilled for each of the two hole sizes. An independent labora-tory verified the holes in a sample of the blister packs byscanning electron microscopy. In addition, any blister packscontaining holes which were not detected as leaking or anygood blister packs incorrectly identified as leaking wereinspected after testing by scanning electron microscopy. A holewas laser drilled in one blister pocket for each of the test blisterpacks in a random location with the remainder of the blisterpockets remaining defect
