Feature Article

MANUFACTURING

MANUFACTURING

Defining the tests

Table II: Advantages and disadvantages of pressure decay leak testing. (click image to enlarge)

There are two main areas of medical device manufacture that require leak detection for quality assurance (QA). Product testing, which includes verifying the function of devices, flow paths, valves and assembly integrity. Pack testing is required to ensure that the sterility of the devices (or other protective requirements such as low humidity) is maintained during the product’s storage and shelf life.

The test methods in common use for testing both packs and products can be broadly separated into two types: pressure decay testing and trace gas testing. Both methods use gas as a medium for detecting flow (except in the case of high pressure testing for interventional balloon catheters). In pressure decay, a pressure differential is set up across the test part, and flow from one side to the other is monitored. In trace gas testing, an easily detected gas is concentrated inside or outside the test part; the presence of this gas on the other side will indicate a flow path.

Pressure decay testing process

Pressure decay testing requires the setting up of a pressure differential across a potential leak. In principle, it does not matter whether the pressure is higher or lower inside the test part compared with the reference pressure, there must merely be a differential. Pressure is then monitored on one side of the differential. A flow, and hence a leak, will be indicated by a gradual change in pressure. If the volume of the space is known, then the rate of change of pressure can be used to calculate the leak rate; this is usually calculated electronically. Table I provides examples of where pressure decay has been successfully applied.

The test method

Pressure decay testing is frequently used in product testing. Many products have a luer connector to provide a convenient point to pressurise the product. For example, a central venous catheter could be connected to a leak test machine that applies air pressure through a luer at one end of the product. If the exit to that particular lumen at the other end of the product is blocked, any flow detected by the equipment will identify a leak on the outside or between the lumens. Many leak detectors have valve controllers that will allow seals to be opened and closed during a test cycle to individually test multiple lumens. This method is known as positive internal pressurisation. Sophisticated electronic equipment can apply precise pressures and monitor pressure changes at sufficient frequency to allow detailed graphing of the pressure changes. Pressure profiles can be ramped or stepped, which is ideal for measuring valve opening pressures, or to measure product or package strengths. This also allows a bond strength test to be combined with an integrity test. Many machines also offer a vacuum cycle that can be used following balloon inflation to draw it back down.

Pressure decay can be used as a simple flow test. The simplest use of this is after an integrity test when a valve is opened in the tooling or fixturing to permit the pressure to escape through a specific route. In this way, the patency of the fluid path can be tested (occlusion test). The pressure transducer can be replaced by a mass flow transducer for more sophisticated (and rapid) flow tests and occlusion tests.

Typically, internal pressurisation is not a destructive test and it can, therefore, be applied as an inline test to provide 100% inspection. The electronic basis of pressure decay testing makes it suitable for automated production systems. There is some restriction on this because cycle times can be 10 or 15 seconds, but multiple test stations may provide a solution.

When extremely high test pressures are required such as when testing stent deployment catheters, compressible gases are to be avoided, but hydraulic testing may be used (test pressures as high as 3000 PSI may be required.)

The pressure decay concept can be reversed to make it into vacuum decay test or a negative pressure leak test. Typically, in this case the product or pack is placed in a test chamber and pressure outside the test piece is reduced. This method commonly uses gases to test packages in which impermeable web materials are used. The test method is sometines used for permeable packages with special tooling.¹ Table II lists some of the pros and cons of pressure decay testing.

Tracer gas testing process

Tracer gas testing also uses the transmission of a gas through a leak as its test medium. It uses a gas concentration differential set up across a potential leak (and possibly also a pressure differential). An elevated concentration of an easily detected gas is introduced, usually inside the test part. Detection equipment is then used to identify any transmission of the gas through a leak. Gas concentration is monitored on one side of the concentration differential. The concentration of any test gas that has found a leak path is measured by equipment that is capable of identifying the leak flow rate and its location. A variety of tracer gases is available, the most commonly used are carbon dioxide (CO₂), hydrogen (H₂) and helium (He). An ideal tracer gas has a reliable quantitative detection method, low natural abundance, low viscosity and low cost.

CO₂ has relatively high natural abundance and is therefore less sensitive than the other methods, which are more suitable for sterile barrier testing. CO₂ is ideal when moisture ingress to a pack is of concern rather than microbial contamination. Both H₂ and He are excellent for testing medical devices and packs. They allow testing with extreme sensitivity and dissipate rapidly to allow repeat or complex testing. H₂ and He test methods have sufficient sensitivity to serve as a proxy for microbial ingress testing.²

The test method

Trace gas testing consists of loading the product with trace gas and then searching for leakage of that gas from the device or pack. Trace gas loading can be performed by low pressure flushing into a device or component (or into a pack prior to sealing). Alternatively, the finished test items can be “soaked” in an atmosphere of trace gas prior to testing. Subassemblies can be sealed in an atmosphere enriched with the trace gas.

Once the gas is loaded, specific detectors are used outside the test piece to detect diffusion or leakage of the gas. The gas used determines the detection method that is required. CO₂ is detected by infrared analysis, H₂ by ion selective absorbtion into a semiconductor, and He by mass spectrometry.

Testing for leakage of the trace gas from the product can be manual or automated. This test method is suitable for 100% inspection or audit testing. The detection systems for He require a deep vacuum and are more cumbersome and costly than those for H₂. H₂ also has the advantage of simplicity of use and accessibility with minimal training. Table III provides examples of where trace gas testing has been successfully applied.

Pack testing example

Sealed, impermeable packs may be tested by pressure (or vacuum) decay or trace gas testing. Medical device manufacturers are sometimes nervous about the regulatory implications of introducing a trace gas at sealing and prefer a vacuum decay test.

Table III: Suitable applications for trace gas testing. (click image to enlarge)

Table IV: Trace gas leak testing. (click image to enlarge)

For the vacuum decay method, the pack is placed in a sealed chamber from which a partial vacuum is drawn. If a leak is present across the pack, the pressure outside the pack will gradually increase as air or gas transfers from the pack to the chamber. The size of the leak can be quantified by comparing the speed of pressure change with a reference leak source. The accuracy of this method is dependent on the volume of the leak from the pack being a significant proportion of the volume of the vacuum chamber. Small pressure changes can be measured, but the pressure changes in testing can be so tiny that movement of seals and temperature changes are just as important; they introduce noise and long settling times, which are particularly a problem for vacuum packs.

Unless there is a reservoir of air in the pack, the H₂ (5% H₂ and 95% nitrogen volume/volume) or the He trace gas test is often more reliable and requires only simple tooling. The pack is placed in a “soaking” chamber that contains an atmosphere of the gas at elevated pressure. The trace gas will enter the pack if there is a leak and in 2 to 48 hours the gas inside and outside the pack will be in equilibrium (the soaking time and pressure can be calculated according to pack specifications). The pack is then placed in a second chamber and examined for H₂ or He being released from the pack. H2 is chosen for low viscosity, rapid diffusion and lower costs, whereas He mass spectrometry can detect the smallest of leaks.

Testing permeable packs

Integrity testing of packages with a permeable element can be conducted manually using the method described in ASTM F 1929-98, Standard Test Method for Detecting Seal Leaks in Porous Medical Packaging by Dye
Penetration (www.astm.org).

There is also a method described for applying trace gas testing to permeable packs. This is in ASTM F 2228: Standard Test Method for Non-Destructive Detection of Leaks in Medical Packaging which Incorporates Porous Barrier Material by CO₂ Tracer Gas.

A nondestructive test method for pressure decay testing of permeable packs is described in ASTM F 2338: Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method.

Product testing example

A typical product tested by pressure decay analysis would be a multilumen catheter or a balloon catheter. With a blood flow measurement catheter there are at least four channels to consider. The first for injecting the bolus of cold saline, the second for inflating the balloon to “float” the catheter into position through the right side of the heart, the third for the thermistor to measure the temperature profile, and a final channel for sampling at the distal tip of the catheter. Two lumens are open at both ends and have a luer connector at the proximal end. The third has a luer connector and is closed by the balloon. The electrical lumen is closed at both ends. Risk analysis establishes that blood loss through the electrical lumen is only feasible if both ends of this lumen become unblocked. The stability of the thermistor cover is, therefore, the main concern. A pressure test prior to subassembly stage may be applied to assess the robustness of this bond.

For pressure testing, the three luer connectors are attached to a sequential pressure decay tester. The open lumens are pressurised in turn with their distal ends initially sealed and then opened to test for integrity and occlusion. The sealing clamps require tooling operated by the leak tester. This tooling incorporates a restrictor for the balloon. The balloon channel is inflated initially and then actively deflated by vacuum. Pressure loss during the inflation phase will indicate a leak.

This open lumen examination can also be performed using a trace gas test. A low-pressure flush of H₂ in nitrogen is introduced through the first luer. The detector is connected in turn to each open lumen. Interchannel leaks and external leaks will be found by the detection of trace gas in particular areas. Table IV lists some of the pros and cons of pressure decay testing.

Selecting the right method

Leak and flow testing are an important QA process for a variety of medical and in vitro diagnostic devices. There are several ways to perform testing, with much overlap between their applications. The principal methods of pressure decay and trace gas testing can be applied to the majority of devices. Method selection is often based on the requirement for automation, the required speed of testing, allowable leak rate, volume of the test part and previous investments. Trace gas testing with H₂ or He offer greater sensitivity than pressure testing (pressure decay being able to detect flows greater than 10-2 mL/s; the H₂ method has sensitivity from 5x10-7 ml/s3). Pressure testing is favoured when valve or strength testing is combined with integrity testing.

Mark Turner is Sales Director at Medical Engineering Technologies Ltd, 41 Seabrook Road, Hythe CT21 5LX, UK, tel. +44 845 458 8924, e-mail: m.turner@met.uk.com, www.met.uk.com