YY/T 0681.18-2020 English PDF (YYT0681.18-2020)
YY/T 0681.18-2020 English PDF (YYT0681.18-2020)
YY/T 0681.18-2020: Test methods for sterile medical device package--Part 18: Nondestructive detection of leaks in packages by vacuum decay method
PHARMACEUTICAL INDUSTRY STANDARD
OF THE PEOPLE REPUBLIC OF CHINA
Test methods for sterile medical device package - Part 18:
Nondestructive detection of leaks in packages by vacuum
ISSUED ON: MARCH 31, 2020
IMPLEMENTED ON: APRIL 01, 2021
Issued by: National Medical Products Administration
Table of Contents
Foreword ... 3
Introduction ... 5
1 Scope ... 7
2 Normative references ... 7
3 Terms and definitions ... 7
4 Overview ... 9
5 Significance and application ... 10
6 Instruments ... 10
7 Danger (source) ... 13
8 Instrument preparation ... 13
9 Calibration and standardization ... 14
10 Programs ... 14
11 Reports ... 15
Appendix A (Normative) Vacuum decay leak test theory ... 17
Appendix B (Normative) Determination of critical test parameters and verification of test sensitivity ... 21
Appendix C (Informative) Precision and bias ... 23
References ... 31
Test methods for sterile medical device package - Part 18:
Nondestructive detection of leaks in packages by vacuum
This Part of YY/T 0681 specifies the test method for the non-destructive detection of the leakage of the packaging system of sterile medical devices, by the vacuum decay method.
This Part applies to rigid and semi-rigid trays without lids, trays or cups with porous barrier covers, nonporous rigid packaging, nonporous flexible packaging. 2 Normative references
The following documents are essential to the application of this document. For the dated documents, only the versions with the dates indicated are applicable to this document; for the undated documents, only the latest version (including all the amendments) is applicable to this standard.
GB/T 19633.1 Packaging for terminally sterilized medical devices - Part 1: Requirements for materials, sterile barrier systems and packaging systems 3 Terms and definitions
The following terms and definitions apply to this document.
Baseline vacuum decay
The degree of change in vacuum within the test chamber over time, as evidenced by non-leaking control packages.
Control, non-leaking packages
Defective packaging, which is properly sealed or closed, in accordance with the manufacturer's specifications.
airflow rate into a test chamber, to verify instrument sensitivity. Airflow meters should be calibrated to a suitable standard. The operating range of the airflow meter should be such that the desired sensitivity limit for the intended leak test is obtained. 4 Overview
4.1 Place the test package in the test chamber, to apply vacuum. The test chamber is isolated from the vacuum source; the pressure sensor (absolute pressure or gauge pressure) is used alone or in combination with another differential pressure sensor, to monitor the vacuum degree in the test chamber and the change of vacuum over time. Vacuum decay, or pressure rise in the test chamber, is caused by the gas in the headspace of the package being drawn out of the package through any leaks, as well as background noise. Vacuum decay can also be caused by volatilization of liquid, within the package that partially or completely enters the leak path. For this case, vacuum decay can only occur, when the test pressure in the test chamber is lower than the vapor pressure of the liquid.
4.2 For the tray or cup with the porous barrier cover material, the leakage located on the tray or holder cup body, as well as the joint between the cover material and the tray, can be tested. Leaks in the porous lid itself cannot be detected. When testing this type of packaging, take measures to physically cover or block the surface of the porous barrier material, to prevent the escape of packaging gases through the porous lid. This may require some sample preparation, depending on the method of occlusion required, BUT must be non-destructive and non-invasive. Vacuum decay in packages, which have a porous barrier lid material, may include background noise from the gas, between the lidding material and shielding surface, OR from lateral airflow through the porous barrier material itself at the lid/tray's seal junction.
4.3 The sensitivity of the test depends on the design of the package under test, the sensitivity of the sensor, the design of the test chamber, the design of the test system, the critical test parameters of time and pressure. The choice of test system and leak test parameters for any given product packaging system must be based on the contents of the package (liquid/solid with large/small headspace gas) and the nature of the package (soft or rigid, porous or nonporous). When the instrument has a more sensitive pressure sensor AND the void volume in the test chamber is the smallest, the test system has the potential to detect the smallest leak. Extended test times can detect smaller gas leaks. Minimizing background noise pressure fluctuations also improves test sensitivity. For packaging with a porous barrier lid material, occluder technology can minimize background noise. For flexible packaging or semi-rigid packaging, the expansion of the packaging can be limited to reduce noise, by rationally designing the test chamber. Release of trapped gas or trapped water vapor, in the test system or between package components under test, may also contribute to background noise. This noise can be distinguished from an actual leak, by extending the test time, to allow the vacuum to return to the initial level, OR by extending the equilibration time.
Note: See Appendix A for more information on "Leak test theory". Examples of experimental methods and test instruments, which are used to obtain precision and bias data, are given in Appendix C and summarized in Table C.1.
5 Significance and application
5.1 Leaks in medical device packaging may result in the ingress of unwanted gases (most commonly oxygen), harmful microorganisms, or particulate contaminants. Package leaks may manifest as defects in the package components themselves or in the sealed joints between package components. Ensuring the consistency and integrity of packaging is an essential capability for leak detection.
5.2 After initial setup and calibration, a test operation can be semi-automatic, fully automatic or manual. This test method is capable of non-destructively detecting leaks, that are not apparent. The test method does not require the introduction of any foreign materials or substances, such as dye solutions or gases. However, it shall be noted that the surface of all porous materials needs to be physically blocked during the test, to prevent the gas from passing through the porous surface and causing the vacuum in the test chamber to drop rapidly. Because this test method is only based on the detection of pressure changes in the test chamber, which are affected by the leakage of gas or steam from the challenge package.
5.3 This test is a useful research tool, for optimizing package sealing parameters and for comparative evaluation of various packages and materials. Because of its rapidity, non-invasiveness, non-destructiveness, this test method is also suitable for installation on the production line, or for 100% online testing of products, or for statistical sampling testing.
5.4 For the vacuum decay test, leak test results exceeding allowable limits may be indicated by an acoustic or optical signal response (or both).
6.1 Vacuum decay leak detection instrument
The vacuum decay leak detection instrument consists of a test chamber, which is connected to the vacuum decay test system, AND a volume flow meter.
6.2 Test chamber
The test chamber has a lower chamber for accommodating the test package AND an upper chamber for closing the test chamber. Figure 1 shows a test chamber, which is dedicated to testing packaging with a porous barrier lid. The test fixture is covered with an elastic bladder, that is used to cover the package's porous barrier during testing. Figures 2 and 3 illustrate the test chamber, which is used for testing nonporous rigid Note: Different leak testing instruments, based on the type of packaging (e.g., rigid or non-rigid, porous or non-porous) and the vacuum required for the test, may use different types of pressure sensors or combinations thereof.
6.3.1 Comparison between absolute pressure sensor and gauge pressure sensor All instruments include a transducer to monitor the test pressure throughout the test cycle. Absolute pressure sensors are preferred over gage pressure sensors, when accurate and true pressure readings are required (i.e., unaffected by changes in atmospheric pressure due to climate or altitude). When performing liquid leakage tests under high vacuum, an absolute pressure sensor is used.
6.3.2 Differential pressure sensor
Can be used as a second sensor, to measure the smallest detectable leaks on rigid/semi- rigid non-porous packaging.
6.3.3 Vacuum source
Select the appropriate vacuum pump, based on the target vacuum level, which shall be able to achieve the vacuum level, within the allocated time, under the given test instrument system headspace conditions.
6.4 Cover or plug
During the test, the porous barrier closure package must be shrouded or plugged, to minimize the escape of air in the package through the lid. Various occlusion techniques can be used, including an elastic bladder on the upper test chamber (see Figure 1). 6.5 Volumetric airflow meter
An adjustable volume flow meter is placed in the test chamber tubing, to introduce artificial leaks at different rates. An airflow meter is recommended, to verify the sensitivity of the leak test.
7 Danger (source)
There is a possible pinch hazard, when the test chamber is closed (source). 8 Instrument preparation
Test instruments shall be powered on, warmed up, prepared, according to the manufacturer's specifications. For instruments with self-contained air-driven vacuum pumps, the required configuration for instrument operation includes a power supply in accordance with the manufacturer's specifications and a source of dry, lubricant-free compressed air. For instruments with an external vacuum pump, the configuration required for instrument operation includes a power supply that complies with the instrument and vacuum pump manufacturer's specifications.
9 Calibration and standardization
9.1 The instrument shall be calibrated, before being put into the test. Pressure transducers, all available vacuum source gauges, adjustable volume flow meters shall be calibrated, according to the manufacturer's recommended procedures and maintenance schedules.
9.2 The instrumentation test system should be leak tested, to verify that it has a stable baseline leak rate. In general, the test parameters are qualified, according to the system qualification test procedure, which is recommended by the instrument manufacturer. 9.3 Critical test parameters shall be set for each package/test fixture combination. Parameters will vary, depending on the test package geometry and the inherent air permeability of any porous material surface. A small number of non-leaking control packages or a simulated non-leaking package shall be used, to select critical parameter settings.
Note: See Chapter 4 and Appendix A for critical test parameters.
9.4 Critical test parameters shall be optimized, using a larger number of non-leaking control package samples. Control packages are fabricated from materials of the same design as the test units.
9.5 Determine the sensitivity of the optimized leak test, using the non-leaking control test pack and a calibrated volumetric flow meter.
9.6 Identify the ability of the optimized test to reliably distinguish between known leak- free and defective packages.
9.7 The test system baseline identification (see 9.2) and test sensitivity verification (see 9.5) shall be carried out regularly, at least once or several times a day, preferably before the start of each shift.
10.1 Select and install a test chamber which is suitable for the size of the package to be tested. Make any necessary adjustments to the test chamber, to ensure that the lid of the test chamber (upper chamber) is sufficiently airtight to the lower packaging chamber (lower chamber), when the test chamber is in the closed position.
10.2 Verify the attainable pressure level at the air source. Check the performance of the vacuum source.
Vacuum decay leak test theory
A.1 The vacuum decay leak test is performed by exposing the package under test to an external vacuum. The pressure differential applied to the package causes the air to escape, through the leak path in the package. If the package contains a liquid, the vacuum below the vapor pressure of the liquid will also volatilize the liquid in or near the leak path. During a test cycle, one or more pressure transducers monitor the pressure rise in the test chamber, as a result of migration of headspace gas and/or volatile liquid in the package through leaks in the package plus background noise. Leak detection requires vacuum decay over background noise. Background noise decay may be caused by expansion of the package when exposed to vacuum or the presence of traces of gas or water vapor in the test chamber or in the test system tubing. The background noise can be minimized by improving the design of the test chamber, adjusting the pressure or time parameters, or exposing the test chamber to vacuum for a period of time, before the test sample is loaded into the test chamber.
A.2 The packaging containing the porous barrier lid material can physically cover or block the surface of the porous barrier of the package, so that the amount of air released through the porous barrier material is minimized before testing. Defects in the gas barrier lid cannot be detected, but defects in the seal area or the tray itself can be detected. Vacuum decay from gas barrier lid material packaging may include background noise from gas between the lid material and the closure surface, or lateral airflow through the seal joint between lid material and tray.
A.3 A typical test cycle is to first place the test package into the test chamber and cover or block any porous barrier packaging surface. Vacuum the closed test chamber. At the end of a predetermined time period, bring it to the initial target vacuum; isolate the test chamber from the vacuum source. After a short equilibration period, the vacuum in the test chamber is monitored, for a predetermined test time. For many packages, it may take only a few seconds, from the time the test chamber is closed to the completion of the test cycle. Various critical test parameters, such as test cycle time, pressure, leak test acceptance criteria, are described below. Figure A.1 shows a typical test cycle, that is expected with various leak test failure modes.
Note: The terms of critical test parameters used in the following clauses may be different from those used by leak manufacturers, BUT the definitions remain consistent. test cycle. The test vacuum is expressed in the pressure unit mbar or Pa. Some devices use vacuum (negative pressure) to represent the test vacuum, whilst others use absolute pressure to represent the test vacuum. Both are as shown in Figure A.1. A.3.5 Vacuuming time and reference vacuuming time
The reference vacuuming time is the allocated time, to reach the target vacuum; the actual time necessary to reach the target vacuum is the vacuuming time. Both the vacuuming time and the reference vacuuming time are expressed in seconds. If the programmed test cycle is to monitor vacuum rise (or absolute pressure drop) during this period, THEN, use the reference vacuum setting and reference vacuuming time specifications.
A.3.6 Equilibration time
The equilibration time is immediately after the vacuuming time. The equilibration time (indicated by s) is to stabilize the pressure fluctuation in the test chamber AND take into account the escape of gas in the gap around the package (for example, from around the screw cap). Typical equilibration times are a few seconds, but can be very short (< 1 s) when rapid pressure rises (i.e., loss of vacuum) as liquids evaporate from the leak space need to be examined.
A.3.7 Test time
The test time (indicated by s) immediately follows the equilibration time, during which the test vacuum is continuously monitored for evidence of package leakage. The same pressure sensor is used to measure the vacuuming time, equilibration time, test time. During the test time, another differential pressure sensor with greater sensitivity can also be used, to detect the pressure change caused by the smallest leak. A.3.8 Reference vacuum
The reference vacuum is defined as the vacuum, that must be maintained in the test chamber after reaching the target vacuum and throughout the equilibration time and test time. The reference vacuum is a vacuum, which is slightly lower than the target vacuum or test vacuum, expressed in mbar or Pa. When absolute pressure is used, the reference vacuum is slightly higher than the target vacuum or test vacuum.
A.3.9 Reference vacuum decay
The reference vacuum decay is defined as the maximum allowable vacuum drop (or rise in absolute pressure), over the test time. The reference vacuum decay can be expressed in the pressure unit Pa or in the pressure change unit (Pa/s). A.4 When one of the following situations occurs, the test package is identified as rejection (?€?failure?€?):
Determination of critical test parameters and verification of test sensitivity B.1 Procedures for determining critical test parameters
The critical test parameters (vacuum purge before test, vacuuming time, equilibration time, test time) of each cycle time, the establishment of each pressure (reserve vacuum, target vacuum and reference vacuum), vacuum decay (reference vacuum decay) require support by knowledge and experience in packaging for testing. It is recommended that the user of the instrument consult the instrument operation manual for more detailed information. B.1.2 ~ B.1.6 describe methods that can be used to establish critical parameters for leak testing.
B.1.2 Determination of target vacuum and (reference) vacuuming time
In order to determine the test vacuum (high enough to detect significant package leaks, without causing a breach of the package seal) and the time period required to achieve this typical vacuum level (evacuation time), a group of leak-free control packages are exposed to various vacuum levels for 1 s or longer vacuuming times of a few seconds. Once the target vacuum is selected, a reserve vacuum slightly higher than the target vacuum is selected, in order to ensure that the target vacuum continues to apply to the non-defective control packages. When testing the leakage of a package with headspace gas, the target vacuum can be set, within the pressure (absolute pressure) range from +2.5 ?? 104 Pa (+250 mbar) to +5 ?? 104 Pa (+500 mbar). When the leaks are partially or completely blocked by liquid, in order to ensure that the liquid evaporates, a higher target vacuum condition of 0 Pa (0 mbar) to +100 Pa (+1 mbar) is required. B.1.3 Determination of equilibration time
When testing against control leak-free packages, choose the equilibration time, by observing how long it takes for the test vacuum to stabilize. When testing for leaks, the equilibration time shall be very short (typically < 1 s), so that the rapid pressure rise due to liquid volatilization can be me...