ISO 80369 Part 7, the long-awaited replacement to ISO 594, introduced a number of changes to the standard governing dimensions and performance requirements of Luer connectors. Its publication in October 2016 capped a monumental change in the fundamental thinking surrounding devices that transfer liquids and gases in healthcare settings. Despite the Technical Committee’s desire to disrupt as little as possible surrounding the current practices with Luer connectors, ISO 80369-7 still makes many significant changes.

This article highlights the changes that most significantly affect how one should construct a design verification plan. Those changes include:

• Stricter requirements on dimensional and mechanical specifications.

• Testing against slip and lock reference connectors.

• Modifications to assembly and test procedures.

• Addition of guidance for performance of variable tests.

As should be expected with changes of this magnitude, there are many nuances in the new standard that require some interpretation.

Why the Change? Prior to ISO 80369, every small-bore connector was a Luer and, under ISO 594, there was a lot of design leeway on what those Luers looked like. ISO 80369 aims to reduce variation in order to prevent errors in connecting to the patients; errors that were sometimes fatal.

What Is the Difference Between ISO 594 and ISO 80369? Compliance to ISO 594 requires two things: gauging (for which failures could often be justified away) and meeting performance requirements. ISO 80369-7 requires three things: full compliance with materials, dimensional requirements, and performance requirements. All three are required in order to maintain the assumption of non-interconnectability.

STRICTER REQUIREMENTS ON DIMENSIONAL AND MECHANICAL SPECIFICATIONS

Prior to the implementation of ISO 80369-7, the ubiquitous use of Luer connectors made it possible for two incompatible devices to be accidentally connected, which could lead to patient injury. The principal goal of ISO 80369 is to reduce the likelihood of these adverse events by introducing unique connector designs for different medical applications whose geometry makes it extremely difficult to make these harmful connections.

One consequence of using the geometry of the connectors to preclude misconnections is that the connectors now need to be measured to ensure that they meet the dimensions and tolerances of the prints in the standard. This differs dramatically from ISO 594, where as long as connector performance could be proven against a reference standard, the dimensions of the connector largely did not need to precisely match the standard. This is by far the most burdensome new requirement resulting from the standards change and many in industry are incredulous to learn that their thread design that has performed adequately must now be changed.

In addition to stricter dimensional requirements, there are also new restrictions on what materials may be used to construct Luer connectors. The elastic modulus of the materials must be greater than 700 MPa when tested in either tension or flexure per standard ASTM methods. Some polymers commonly used as Luer connectors do not meet this requirement, including many polyethylenes.

TESTING AGAINST SLIP AND LOCK REFERENCE CONNECTORS — WHEN IS IT REQUIRED?

The separation of ISO 594-1 for slip Luers and 594-2 for locking Luers created a convenient distinction between their separate requirements, but also a lack of clarity about if and when both sets of tests needed to be performed. ISO 80369-7 contains both requirements within the same document but is still not explicit about when one should invoke the tests against both slip and lock reference connectors.

This is an important consideration when qualifying a female locking Luer, as both male slip and locking Luers can easily be connected. The simplest answer is that if a device with a female locking Luer is intended to connect with a specific device that has a male locking Luer, then the female locking Luer only needs to be tested against the male locking reference connector. If the device’s use is not as specific, or if it’s uncertain, then both sets of requirements are in play. Table 1 lists the test requirements for each possible configuration.

Table 2. Assembly parameters of ISO 594 and 80369.

MODIFICATIONS TO ASSEMBLY AND TEST PROCEDURES

One of the critical elements of ISO 594 was a standardization of the torque and axial force used to assemble a test sample to a reference connector. ISO 80369-20, which is the standard that defines how to conduct the test methods, narrows the range of acceptable torque and axial force, utilizes the same assembly values for every test, and clarifies the assembly procedure for products with floating or rotatable collars. Table 2 outlines the assembly parameters of ISO 594 and 80369. In addition to changes in the assembly parameters, many of the tests have changed substantially as well; titles and test parameters have been modified, new tests have been added, and the ease of assembly test was eliminated because of its subjectivity. Table 3 compares and contrasts some of the most significant changes to each test.

ADDITION OF GUIDANCE FOR PERFORMANCE OF VARIABLE TESTS

Annex J in ISO 80369-20 contains specific instructions and guidance on how each test can be modified in order to obtain data of a variable (numerical) type, which may help to reduce the sample size needed in order to achieve the desired confidence intervals. For some tests, e.g. sub-atmospheric pressure air leakage, the change is trivial, only requiring one or two additional calculation steps.

For others, like the positive pressure falling drop liquid leakage test, the apparatus used to perform the variable test method requires additional levels of control beyond what is needed to perform the attribute test method. The determination of whether or not to utilize the variable methods is typically made on a case-by-case basis and takes into account the potential extra test method validation work, fixturing, and increased cost for tests that require more time and complex equipment to perform.

IS NON-INTERCONNECTABILITY TESTING A REQUIREMENT?

ISO 80369-1 states that small-bore connectors of each application category shall be non-interconnectable with any of the small-bore connectors of every other application category, unless otherwise indicated in ISO 80369-1 or within the ISO 80369 series. Based on this, manufacturers will need to demonstrate that the small-bore connector under test exhibits non-interconnectable characteristics when evaluated against connectors of other application category, in addition to ensuring that they safely and securely connect with their mating half.

If a small-bore connector meets the dimensional compliance and modulus of elasticity compliance within the requirements of the various application parts of the ISO 80369 series, it is considered sufficient objective evidence of non-interconnectable characteristics. If a small bore-connector does not meet both of these requirements, then the methods of ISO 80369-1 are to be used.

There are two different ways to show that a small-bore connector meets the criteria of non- interconnectability per ISO 80369-1. The first is to run a dimensional analysis comparing all of the different parts of the connector to other connector application types. Annex B.2 in ISO 80369-1 provides detailed instructions regarding how to perform this dimensional analysis. It takes into consideration the least material condition (LMC) and maximum material condition (MMC) of all of the parts to ascertain whether they will incidentally connect when assembly of the parts is attempted.

If it is determined through this dimensional analysis that a part could connect to a different small-bore connector, the feature, or as the standard calls it the “potential mating surface,” which a given part is being evaluated against would need to be created and then tested in the physical test in Annex B.3. The mating surface needs to comply with the material requirements in Annex B.2 to be a valid part to test against.

The second method to show that a sample meets the criteria of non-interconnectability is to run the physical tests that are described in Annex B.3 of ISO 80369-1 against a target reference connector. The target reference connector is either determined from Annex B.2 or other connections as identified by the manufacturer. In many cases, the metal reference connectors from the different application categories, other than the type of small-bore connector being tested, are used as the target reference connectors for this evaluation.

When running the physical assembly test, if a small-bore connector assembles to another metal reference connector, a leakage test will then be run on the connectors that assembled are together. This leakage test is used to evaluate whether the connection between the two connectors is poor and would be an obvious misconnection to a person using the part in the field.

Alternative designs of small-bore connectors not defined in the ISO 80369 series may be used in medical device or accessory applications, and if used they must be evaluated to the non-interconnectable characteristics requirement in Annex B of ISO 80369-1. In order to comply with this requirement, the alternative design will need to be evaluated according to the engineering analysis of Annex D.3 and comply with the materials characteristics requirement.

WHAT IS THE RECOMMENDED SAMPLE SIZE?

ISO 80369 does not carry special provisions for sample size. Like all testing, sample size should be derived from risk and the desired confidence level. There are multiple test methods in 80369 and each one must be considered and assigned a risk level independently of the others. For example, if it is determined a sample size of 60 is necessary for testing, that equals 60 samples per method, not 60 samples across all methods.

All in all, variable methods can be a great option in situations where high-risk attributes mandate very high confidence and reliability, or when the sample connectors are expensive or in limited supply, but there are also significant complications that need to be addressed. In many cases, the value of performing variable analysis is more difficult to realize than it initially appears.

CLOSING CAVEATS

On December 23, 2016, the FDA added ISO 80369-7 to its list of recognized consensus standards. As of the publication of this article, the FDA web site states that the agency will continue to accept declaration of conformity to ISO 594 in support of premarket submissions until December 17, 2023.

Finally, this article is intended to give a high-level overview of the differences between ISO 594 and 80369-7 and is not intended to be a substitute for a comprehensive understanding of the contents of the standards and how they may affect design and testing.