medical device testing Archives

ISO 11040-4:2024 – Key Updates You Need to Know

The release of ISO 11040-4:2024 marks a significant evolution in the standards for prefilled syringes, replacing ISO 11040-4:2015. This new edition brings crucial updates that align with the latest industry practices and provide improved clarity across the standard by reformatting and numbering various sections. In this blog, we’ll dive into the most important updates introduced in ISO 11040-4:2024.

1. Enhanced Quality Systems, Testing, and Documentation

One of the standout updates in ISO 11040-4:2024 is the heightened focus on adhering to formal Quality Management Systems (QMS).

Key changes include:

All documentation and testing processes must now comply with a formal QMS.
Test equipment used in syringe production must be qualified to guarantee accuracy and consistency.
Test methods must be validated to ensure they are appropriate for their intended purpose.
Electronic records and handwritten signatures related to validation, process control, or quality decisions must be meticulously documented and retained in line with QMS standards.

These updates aim to foster greater consistency and transparency throughout the production and testing process, ensuring a higher level of control over quality and traceability.

2. New Design Requirements for Staked Needle Syringes

Another major revision in ISO 11040-4:2024 involves the specific requirements for staked needle syringes, which are commonly used in prefilled syringe applications. These updates focus on ensuring clear communication and alignment between manufacturers and clients.

The new guidelines include:

Agreement on the needle diameter and length as well as the finger flange design between both manufacturer and client.
A new tolerance table has been introduced, covering different syringe volumes and needle lengths for better standardization.
Updated figures depicting typical staked needle syringe designs to provide clearer visual guidance.

These changes are intended to improve collaboration between stakeholders, reducing design misalignment and ensuring higher quality syringe outcomes.

3. Updated Performance Standards for Syringe Components

ISO 11040-4:2024 introduces new performance metrics for syringe components, particularly related to breakage resistance and needle penetration force.

Notable updates include:

Defined minimum force requirements for both finger flange breakage resistance and front end breakage resistance (formerly Luer cone breakage resistance) to prevent syringes from breaking during handling or transport.
A new maximum penetration force for needles has been specified to detect defects in needle points or lubrication that could impact patient comfort.

These updated performance standards ensure that syringes can withstand rigorous use, minimizing the risk of failure and improving patient experience.

4. Expanded Glide Force Test for Non-Lubricated Syringes

Previously, the Glide Force Test Method was only applicable to lubricated syringes. However, ISO 11040-4:2024 now extends these guidelines to cover non-lubricated syringes, which are becoming more prevalent.

This extension allows manufacturers to perform more comprehensive performance assessments, ensuring that non-lubricated syringes meet the same quality benchmarks as their lubricated counterparts.

5. Updated Figures for Better Technical and Visual Clarity

To enhance understanding and implementation, the figures throughout ISO 11040-4:2024 have been named and numbered to clearly outline the requirements of each section. These updates offer clearer, more accurate depictions of syringe components and designs, making it easier for manufacturers and quality teams to interpret and apply the standard.

This refinement helps reduce ambiguity and improves technical clarity, which is vital for compliance and product quality.

6. Revised Annex B for Sub-Assembled Syringes

Finally, Annex B has been updated to include additional details about sub-assembled syringes that are ready for filling. This now covers examples of plunger stopper variants and plunger rods, adding to the previous edition’s focus on head designs for glass barrels.

These revisions offer clearer guidance on the components of sub-assembled syringes, providing manufacturers with better insights into the assembly process before filling, which is crucial for ensuring product consistency.

Conclusion

The release of ISO 11040-4:2024 introduces vital updates across quality management, syringe design, performance testing, and sub-assembly guidelines. For manufacturers and quality assurance professionals, staying informed about these changes is critical to maintaining compliance and delivering high-quality products.

Please contact us for more information on ISO11040 testing, or if you need help on an upcoming test.

ANSI/AAMI CN27:2021: A New Benchmark for Luer Activated Valves in Medical Devices

The field of medical device manufacturing continually evolves to enhance patient safety and device reliability. One key development in this area is the publication of ANSI/AAMI CN27:2021, a comprehensive standard that establishes general requirements for Luer Activated Valves (LAVs) used in intravascular applications. Published in December 2021, this standard is essential for harmonizing terminology, setting minimum requirements, and standardizing test methods for LAVs. It serves as the first foundational guide for manufacturers, regulatory bodies, and end users, offering clarity and consistency in the evaluation of these critical components.

The History and Challenges of Luer Activated Valves

Luer Activated Valves have long been integral to medical devices, especially in intravascular applications. Originally developed as needle-free connectors, they are now used in a variety of medical scenarios such as IV access, hemodialysis and close medication delivery systems. The shift towards using a valve compatible with standard fittings or syringes emerged as a response to the need for safer and more efficient, bi-directional fluid control systems. However, these LAVs presented unique challenges as the incorporation of a normally closed-valve design within an ISO-compliant luer distinguished them from the standard luer connectors.

Although there was guidance from ISO 80369-7 on how to evaluate that LAVs were compatible with standard male luer connectors, manufacturers adopted their own specifications to manage the complexities and risks associated with LAV connections. Furthermore, the variety of applications in how the LAV was used led to different product descriptions, performance claims, and instructions for use. As a result, this unfortunately caused confusion among end users which required manufacturers to educate the field on device capabilities and interactions.

Testing LAVs Prior to the Development of ANSI/AAMI CN27

Prior to the standardization of LAVs, testing was primarily conducted per the guidance of Annex A of ISO 80369-7. Within DDL, we have seen that there were two main approaches to showing LAV compatibility. The first approach was to conduct functional testing in guidance against the applicable ISO 80369-7 standard using the mating reference connector outlined in Annex C of ISO 80369-7. The second approach was similar but would involve the mating device (e.g. male luer lock syringe) as the reference connector to show compatibility. In addition, to the performance testing, a majority of our customers conducted the physical test method under ISO 80369-1 to show non-interconnectability characteristics rather than analyzing the specified dimensions from ISO 80369-7, Annex B.

Unfortunately, there were several issues with the guidance that ISO 80369-7 standard provided and the approaches above. As the standard mentions, most LAVs in the field were not compliant to the material requirement (i.e. Elastic/Flexural Modulus ≥ 700 MPa). As a result, conducting ISO 80369-1, Annex B non-interconnectability testing posed challenges if the material was soft as damage could be seen after one run of testing against an ISO 80369 metal reference connector. If the LAV was damaged and connected to the reference connector, it was difficult to determine if the damage caused the connection or if it was due to the design. In addition, the guidance did not account for other critical characteristics of the LAVs such as flow rate, priming/residual volume, and the performance while the valve was unactivated. For example, the performance testing outlined in ISO 80369-7 only challenged the LAV in the activated condition, but did not challenge the device in the unactivated condition to show that the valve was sealing properly. The ambiguity in how to properly characterize these critical elements of the LAVs to show patient safety highlighted the need for a standardized approach.

Key Features of ANSI/AAMI CN27:2021

1. Standardized Terminology and Requirements:
ANSI/AAMI CN27:2021 addresses the inconsistencies that previously existed in the market by standardizing the terminology and requirements for LAVs. This standardization includes precise definitions for terms like microbial ingress, activation number and duration, displacement, and power infusion capabilities. The uniformity in language helps ensure that all stakeholders, from manufacturers to regulators, have a clear and consistent understanding of device specifications.

2. Impact of Terminology on Performance Claims:
The standard recognizes the importance of precise language in regulatory and clinical contexts. For instance, due to the bi-directional nature of the device, the definition of fluid movement as “positive” or “negative” displacement affects how a device’s performance is communicated and understood by the end user. Such clarity allows manufacturers to better identify their device’s performance in order to make accurate, comparable performance claims on these devices now. The comparable performance claims not only promotes competition between manufacturers, but it also allows the end users to objectively determine which devices to use for their patients.

3. Harmonized Test Methods:
One of the critical contributions of ANSI/AAMI CN27:2021 is the harmonization of test methods. By establishing uniform test procedures, the standard enables reliable comparisons of performance claims among different LAV products. This is particularly crucial for making performance claims where consistent testing ensures accurate and meaningful labels. Although the standard outlines a uniform test procedure, there are some areas where testing will differ based on the specific application of the product. For example, manufacturers will still be responsible for understanding the longest intended use period and the number of intended activations/de-activations. Even with different applications, the harmonization of test methods allows manufacturers to mitigate subjective performance data, misleading claims and unintended clinical consequences.

Benefits for Manufacturers, Regulatory Agencies, and End Users

ANSI/AAMI CN27:2021 provides a comprehensive framework that benefits all stakeholders involved with LAVs. For manufacturers, the standard offers clear guidelines for designing and developing compliant devices, facilitating smoother interactions with regulatory agencies. Furthermore, due to the standardization of LAVs, manufacturers no longer have to conduct compatibility testing against specific mating devices to show functional compliance. Regulators, in turn, gain a robust tool for evaluating product safety and efficacy based on standardized criteria. End users, including healthcare professionals, benefit from consistent and reliable product information, reducing confusion and enhancing the safe use of LAVs.

Conclusion

The publication of ANSI/AAMI CN27:2021 marks a significant milestone in the standardization of Luer Activated Valves for medical devices. By establishing clear guidelines and harmonizing terminology and test methods, this standard provides a valuable resource for ensuring the quality and safety of LAVs used in intravascular applications. As the medical device industry continues to advance, adherence to ANSI/AAMI CN27 will be crucial in maintaining high standards of patient care and device performance.

For those involved in the design, regulation, or use of LAVs, understanding and implementing the requirements set forth in ANSI/AAMI CN27:2021 is essential for aligning with industry best practices and ensuring the safety of patients around the world.

For further information, please view the recent video with Matt Pasma, DDL’s Product & Materials Program Manager, in which he provides an overview of DDL’s Luer Activated Valve (LAVs) testing capabilities per the ANSI/AAMI CN27:2021 standard.

Please contact us for more information on LAVs testing, or if you need help on an upcoming test.

DDL Enhances its Medical Connector Testing Capabilities with the Addition of Dimensional Analysis Services

DDL is excited to announce it has enhanced its medical connector testing capabilities with the addition of Industrial CT scanning to provide dimensional testing to meet the exacting dimensional criteria outlined in the ISO 80369 standard. The addition of CT scanning capabilities makes DDL the only third-party lab to offer both mechanical testing and dimensioning services for ISO 80369 compliance in-house.

ISO 80369 is a set of standards created for small-bore connectors utilized in healthcare applications, encompassing the Luer Lock design. Adhering to these standards empowers medical device manufacturers to elevate patient safety, diminish the likelihood of misconnections, and guarantee compatibility between devices from diverse manufacturers.

“DDL is committed to providing our clients with the most cutting-edge solutions to ensure their products meet the highest standards of quality and compliance,” said Matt Pasma, Product & Materials Program Manager, DDL Inc. “The addition of dimensional testing capabilities complements our medical connector mechanical testing services and further solidifies DDL’s leadership as the go-to third-party lab for ISO 80369 validation services.”

For more information on DDL’s Industrial CT scanning capabilities or to receive a quote, please contact us or call us at 800-229-4235.

The Statistics of Sample Size for Testing Medical Devices to Ensure Regulatory Requirements are Met

Choosing the optimal number of samples while testing your medical device product boils down to a common trade-off: cost vs. benefit. Staying within your testing budget is important but ensuring that your data is robust enough to withstand scrutiny from the regulatory body is paramount and avoids costly delays with re-testing. As a 3^rd party contract testing lab, DDL will not make the final determination of sample size for our clients. However, there are common tendencies which we have observed in the sampling that our customers see when submitting device applications. We will outline these tendencies and other observations in the hope that they will be useful for those who are researching how to best structure their testing regimen.

Before discussing the common sampling trends DDL has observed, it is relevant to address pre-design verification activities. Feasibility and characterization testing are often conducted during pre-design verification studies using lower sample quantities than Design Verification. When determining the sample size during Pre-DV, it is important to consider multiple samples per unique design input (e.g. mold cavity) as it may help mitigate any false positives and issues down the road. In addition, the risk of the device’s manufacturing process should also be considered when determining the sample size for these early, initial phase studies.

During design verification studies, the first factor that needs to be made when determining sample size is whether the test data you require will be attribute or variable. Attribute data, also called binomial data, are qualitative results. Pass/fail or go/no-go are common types of attribute data – for example whether a measured dimension falls within the tolerances on the drawing. Variable data output is shown in values. For example, the seal strength of a heat-sealed pouch or the tensile strength of a poly film is typically shown as variable results.

The next factor in determining sample size is evaluating your risk tolerance. An internal regulatory or quality department or a consultant will provide good guidance on risk tolerance. In addition, ISO 14971 is called out by a significant number of ISO standards on how to apply risk management to medical devices which may ultimately be helpful in determining the appropriate sample size. As one can expect, a high-risk product requires more test samples in order to achieve an acceptable confidence interval. Statistically speaking, a higher risk product means that you need to assign a more stringent acceptable quality level (AQL), p₀, to your experimental design. The AQL represents the maximum allowable proportion of defective items in a lot. For example, if a maximum of 5% of your parts can be defective, your p₀ value would be 0.05. From there, using the cumulative geometric distribution function, you can determine your optimum sample size for an attribute test. Similar principles can be applied to variable testing when it comes to risk but instead of a sample size increasing with a higher risk product, the Cpk or K-value will change. Ultimately, the change in these values will make sure the device is still held to higher levels of risk that will ensure that the device is still adequate for use against the appropriate risk assessment.

The most common sample sizes DDL sees for attribute tests are 29 and 59. For example, to obtain a 95% confidence that your product’s passing rate is at least 95% – commonly summarized as “95/95”, 59 samples must be tested and must pass the test. If your product has lower risk and you are able to accept a lower passing rate of 90%, only 29 passing samples are needed to obtain 95% confidence, or “95/90”. These numbers all assume that there will be no failures in any of the samples. That, unfortunately, is not always the case. In the event of an isolated failure, a different equation – the negative binomial distribution, must be used. In order to maintain the same confidence intervals as stated above with one failure, the sample size is 46 for a p value of 0.10 and 93 for a p value of 0.05 and increases with additional failures.

At the end of the day, determining sample size for an attribute test is a straightforward task once the statistical requirements are known, but its importance cannot be overstated. Conversely, with variable testing, there are many product dependent factors to consider before arriving at a sample size quantity. Determining your sample size using either statistical method will not only ensure that regulatory requirements are met, it also provides evidence that the quality of the product is high increasing patient safety.

Medical Device Testing – Benefits of Outsourcing vs. Doing In-House

New technologies, process advancements and the aging population have all led to explosive growth within the medical device industry. This growth has also led to more strict and complex regulations with increased competition. The rising regulatory focus and increasing demand for high quality and standard products across the medical device industry has also driven the need for more rigorous testing to ensure a product’s safety and efficacy. To meet this increasing demand for testing, medical device manufacturers face the classic “make or buy” decision of performing testing in-house vs. outsourcing to a third-party lab.

What are the advantages of outsourcing testing?

Cost Efficiencies

The medical device industry is under constant pressure to control costs without sacrificing research development, timelines or safety. Conducting a successful testing program takes significant resources and operational focus. Thus, a medical device OEM must determine if it is more cost-effective to develop this capability in-house, or will it be more efficient to use an outside lab. In most cases, it will be more cost efficient to outsource to a third-party lab.

When doing testing in-house, the largest and most hidden cost is overhead. Medical device manufacturers have to keep in mind the cost to purchase, maintain, repair and calibrate the equipment, building / facility expense, opportunity cost of space utilization, utilities, insurance and any other sunk costs such as administration / accounting expense. Often times, overhead is not accurately accounted for when evaluating the make or buy decision. Companies rely more heavily on variable or operational costs such as CAPEX, labor and direct materials. As a result, the “make or buy” financial analysis can become skewed. By outsourcing testing, medical device manufacturers can take advantage of lowered operation costs, increased agility, a reduction on time-to-market, which can add up to a boost on their return of investment (ROI).

Testing Expertise

In addition to costs, many medical device OEMs may also not have personnel in-house with the appropriate skill set to perform the testing. Testing programs are successful when directed by trained, experienced, and qualified personnel. Subject matter experts play a critical role in assessing product development needs, test requirements, and study designs. An experienced staff brings real benefits from speed of data analysis, operational efficiencies, enhanced reliability, the ability to support data reviews, and numerous other intangibles.

Establishing a robust QMS (Quality Management System) also requires technical expertise. Hiring competent quality personnel to create and maintain standard operating procedures, protocols, and other quality documents is a critical aspect of a quality management system.

If a company seeks to make a long-term investment in device testing, this should also include hiring staff who are experienced in that particular area. This naturally produces cost tradeoffs—the time spent training this new staff will lengthen the time-to-market for any product still in development, and not all manufacturers may be committed to the ongoing recruiting and development of these specialized roles.

Turn-around Time/Reduced Time to Market

Some tests may make sense to have in-house as the difference in turnaround time is minimal. High volume testing can have lengthy turnaround times when conducted in-house compared to outsourcing.

It is also important to determine if the internal lab meet the project timeline based on overall company priorities and resources, which may conflict. This is especially true of larger companies with multiple divisions or product lines that utilize the same laboratory. Every day and every week that testing is delayed also causes delays in getting the product to market, which could ultimately impact cost more to the bottom line than outsourcing the testing to a third-party lab.

Third-party Perspective/Risk Mitigation

When deciding on outsourcing vs. doing a test in-house, one should also take into account the FDA and other regulatory bodies’ perspective on results generated by the medical device manufacturer versus that of a third-party testing provider. While it is generally assumed a medical device manufacturer would not skew the results in order to pass a test, having an outside lab confirm the results of a test always looks better from the standpoint of the regulatory body.

It is also beneficial to have an independent lab involved when performing validation activities in order to have unbiased verification of R&D test results performed in-house. Consider whether regulatory bodies look more favorably upon tests conducted by reliable third parties versus in-house test results based on the criticality of the test endpoint. Using an external third-party laboratory may remove testing bias, or the perception of testing bias, facilitating the path for regulatory approval.

Conclusion

Outsourcing testing offers numerous benefits that can strategically position MDMs for success. Cost efficiency, access to expertise and resources, reduced time to market, and risk mitigation are some of the advantages that make outsourcing an attractive option. By leveraging the capabilities of specialized testing service providers such as DDL, MDMs can optimize their testing efforts, enhance product quality, and improve their bottom line.

For more information, or to answer any testing questions you may have, please contact us or call us at (800) 229-4235.

A Summary of the Updated ISO 80369-7 Standard

In May, 2021, ISO published the updated 80369-7 standard. ISO first published ISO 80369 Part 7 in October, 2016 as the replacement to ISO 594, the standard governing dimensions and performance requirements of Luer connectors.

Following are some of the highlights of the updated 80369-7:2021 standard:

General

Two different categories for material’s modulus of elasticity:
- Semi-Rigid (700 MPa to 3,433 MPa)
- Rigid (Greater than 3,433 MPa)
Remove the need to ASTM D638 and ASTM D790 in the luer testing. The standard now leans on the requirements of ISO 80369-1:2018 for this part of testing.
Update references to the new versions of standards, Specifically ISO 80369-1:2018

Performance Testing

Unscrewing torque range has been revised to 0.018 – 0.020 N·m

Dimensional Testing

The tolerances for specific dimensions across Annex B have been updated based on the type of material (semi-rigid or rigid) used to manufacture parts
Some dimensions are now considered to be auxiliary
Some tolerances were loosened to make it easier to manufacture the parts.

Reference Connectors

The dimensional tolerances have loosened, easier to calibrate and manufacture
- Note: this does not affect DDL’s calibrated reference connectors

Starting with the publication of ISO 80369-7 in October 2016, the FDA gave manufacturers a three-year grace period to show that parts previously compliant with ISO 594 are now compliant with ISO 80369. Originally the FDA stated it would no longer accept submissions showing conformance to ISO 594 after December 31, 2019. The FDA has since extended the deadline to December 17th, 2023.

The European Union’s joint technical committee is working with ISO on the development of the ISO 80369 series of standards to ensure requirements from the EU directives are met and the standards can be accepted by the EU. Currently the EU has withdrawn the previous versions of the Luer testing standards and as of May 31, 2020 they will no longer accept submissions to the previous versions of the standards.

Once updates are completed to a standard, the EU will give one year before withdrawing the previous version of the standard and requiring compliance with the currently accepted version of a standard.

For more information on ISO 80369-7, please download our white papers “ISO 80369-7: Changing the Standard for Luer Connectors” or “ISO 80369 FAQs”.

Please contact us if you have further questions or need help with an upcoming test project.