If you're performing or outsourcing clinical investigations of a medical device, ISO 14155 is the standard for you.

Good clinical practice (GCP) is as critical for medical devices as it is for pharmaceutical drugs passing through clinical trials.

Understanding and applying the requirements of ISO 14155:2020 is the best way for both sponsors and investigators to ensure the ethical compliance and the scientific validity of the medical device clinical investigation process.

This blog post guide explores the latest version of ISO 14155, outlines its requirements, and explains how your company can meet them.

Introduction to ISO 14155:2020

ISO 14155:2020 is the most recent revision of the international standard titled, “Clinical investigation of medical devices for human subjects – Good clinical practice.”

Like all ISO standards, it was published by the International Organization for Standardization (ISO) with the purpose of harmonizing global practices — in this case, for conducting clinical trials on higher-risk medical devices in a manner that maximizes both scientific rigor and, ultimately, patient safety.

ISO 14155 offers a GCP framework for investigators, like contract research organizations (CROs), and their sponsors to follow together. Outsourced trial providers and their clients should therefore both understand and adhere to the ISO 14155 guidelines.

While not mandatory in all jurisdictions, compliance with ISO 14155 is now  generally expected by many regulatory bodies and ethics committees.

In the EU, it's particularly critical for high-risk device conformity assessments under the MDR, officially known as MDR 2017/745. While in the US, ISO 14155 adherence supports compliance with the FDA's investigational device exemption (IDE) process mapped out in 21 CFR Part 812.

What is ISO 14155?

ISO 14155 provides a comprehensive, globally recognized regulatory framework for the design, conduct, recording and reporting of clinical investigations of medical devices.

Like other GCP standards, most notably ICH E6 (R3) for pharmaceuticals, ISO 14155 aligns with the 14 clinical principles flowing from the 1964 Declaration of Helsinki.

It also aligns with global regulatory clinical expectations including those of the FDA, the European Union, and other competent authorities.

Clinical investigations for medical devices are, as you'd expect, reserved for higher-risk devices with greater impact on patient safety, and the risk classification of the medical device therefore determines whether ISO 14155 is an applicable part of the device's journey to market.

In the US, high-risk Class III devices, and some novel medium-risk Class II devices, require clinical data and investigation, while in the EU, Class III and Class IIb devices require them.

Download medical device classification PDF guide for more guidance

With only about 10% of devices falling into the highest regulatory risk category, and only some medium-risk devices requiring clinical data, only about 15-20% of medical devices pass through a clinical gateway as part of their regulatory submission process.

It's for this group of high- to medium-high-risk devices that ISO 14155 is designed.

It's worth noting, too, that the ISO 14155 guidelines are built for regular medical devices and software as medical devices (SaMD) — not in vitro diagnostic devices, or IVDs. Even so, the ISO 14155:2020 standard itself suggests that some areas of its requirements could be borrowed for IVD clinical investigations.

Why was ISO 14155 updated in 2020?

Like all ISO standards, ISO 14155 has been subject to some tinkering over the years.

Its latest version, released in 2020, updated the previous 2011 version to ensure:

• Alignment (but not formal harmonization) with new global regulations like the EU MDR

• Greater emphasis on risk management: Annex H explicitly recommends the ISO 14971 medical device risk management model to dovetail with your clinical activity

• Enhanced sponsor responsibilities

• Requirements to publicly record clinical investigations, such as in the EUDAMED database in the EU
  
  

• Improved guidance on data management and monitoring

• Integration of patient safety and data integrity considerations

ISO 14155:2011 was also vague on the different types of clinical investigations, and how they relate to different touchstones in the medical device product lifecycle. ISO 14155:2020's Annex I tackles this fuzziness. 

In all, the standard's latest update ensures that ISO 14155:2020 keeps pace with regulatory change while more clearly defining how clinical investigations should be managed with good clinical practice at the core.

Requirements of the ISO 14155 guidelines

ISO 14155:2020 is structured to cover all phases of a medical device clinical investigation, from planning to reporting. 

Let's explore the key areas.

1. Ethical considerations and subject safety

Like any clinical standard, patient rights and welfare are central to ISO 14155.

The standard mandates that:

• Investigations follow the Declaration of Helsinki

• Subjects give informed consent voluntarily

• Independent ethics committees review and approve your study protocol(s)

• Risk-to-benefit ratios are evaluated and documented before the study begins

Only after you demonstrate you have patient wellbeing baked into the core of your operation will your ethics committee and your country's regulatory authority give the green light for your trial to begin.

2. Clinical investigation planning

ISO 14155 offers a broad 'checklist' of ingredients for a clinical plan, rather than a strictly defined model.

Before starting a study, sponsors should:

• Prepare a Clinical Investigation Plan (CIP): the key document of the investigation with proposed objectives, methodology, design, risk analysis, and justification for the decisions you've made

• Prepare an Investigator's Brochure (IB): the summary of any preclinical or existing clinical data to justify the execution of the investigation
  
  
• Prepare case report forms (CRFs) to capture subject data
  
  

• Define primary and secondary endpoints

• Prepare and fully document plans for emergency medical care, subject withdrawal and adverse event management

3. Sponsor responsibilities

Look to Clause 8 of the ISO 14155 guidelines for a full breakdown of what a clinical sponsor needs to do to ensure a high-quality trial.

The sponsor, which is often but not always the medical device's manufacturer, must:

• Ensure all clinical investigations are compliant with ISO 14155, and any local clinical laws

• Choose qualified, competent investigators, who can commit to their own ISO 14155 requirements (more on that below!)

• Ensure quality by design is worked into the fabric of the clinical plan and the documents listed above 

• Assume overall responsibility for the investigation, even when outsourced 

4. Investigator responsibilities

What about the other side of the coin — the investigator actually performing the clinical work?

Clause 9 is where you can dig deeper into these requirements.

In short, principal investigators must:

• Oversee the day-to-day execution of the investigation's CIP

• Work to keep patient safety, wellbeing, rights, and all clinical data constantly safeguarded and under control

• Constantly manage risk during the investigation: see Sections 6.2 and 7 for more information

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  Record and report any adverse events or device deficiencies in accordance with the standard: see Section 7 and Annex F for more information

5. Data management and monitoring

Because high-integrity, trustworthy clinical data is at the core of GCP, ISO 14155:2020 also reinforces data integrity in a number of key ways.

Any electronic data capture (EDC) tools need to be validated, and source data requires full verification with traceable audit trails.

ISO 14155 certification process

We've already seen that ISO 14155 certification isn't a mandatory requirement for conducting a clinical trial.

Nevertheless, aligning with the standard and securing certification is the best way to prove to regulators your commitment to clinical quality, integrity and ethical responsibility.

Start with a thorough gap analysis and internal auditing program of your documentation and your quality management system to position yourself for the certification process.

Once you've established contact with a certifying body, you can expect the typical ISO format of Stage 1 and Stage 2 audits, with Stage 1 focusing primarily on documentation and Stage 2 an on-the-ground assessment of your operation.

ISO 14155 certificates remain valid for 3 years.

But don't neglect your other regulatory requirements, too. ISO 14155 by itself may not cover every clinical expectation in your territory of operation, so do your research.

ISO 14155 FAQs

Got questions about ISO 14155? See if it's on our FAQ list below.

1. How does ISO 14155 relate to ISO 13485?

ISO 14155 focuses on clinical investigation conduct, while ISO 13485 governs quality management systems for medical device manufacturing. However, both standards share a commitment to risk management, documentation, and patient safety.

2. What's the difference between ISO 14155 and ICH GCP?

ISO 14155 is specifically tailored to medical devices, whereas ICH GCP (E6 (R3)) primarily applies to pharmaceutical trials.

Key differences include:

• Device-specific risk expectations (such as usability, software, biocompatibility)

• Greater emphasis on device performance data

• Flexibility in risk classification-based oversight

3. Does ISO 14155 apply to post-market clinical follow-up (PMCF) studies too?

Yes! PMCF studies required under the EU MDR should also meet ISO 14155 best practice to ensure scientific validity, safety monitoring and data integrity — even after market launch.

4. Which requirements are addressed in both the ISO 14155:2020 GCP standard and FDA regulations?

Both ISO 14155 and FDA expectations of clinical investigations share the same essence of maximizing scientific rigor and patient safety.

As such, ISO 14155's emphasis on subject wellbeing is reflected in FDA 21 CFR Part 50 (Protection of Human Subjects) and 21 CFR Part 56 (Institutional Review Boards).

FDA 21 CFR Part 812 (Investigational Device Exemptions) outlines similar responsibilities of clinical sponsors and investigators, including key aspects like study oversight, adverse event reporting and record-keeping.

ISO 14155 certification is therefore a great way to ensure your operation meets clinical requirements for the United States.

5. Can electronic quality systems support ISO 14155 compliance?

Yes. The best electronic quality management systems, like Qualio, offer powerful, integrated digital functionality to simplify and support your ISO 14155 certification journey.

Typical functionality includes:

• Electronic document management for automatic, high-integrity control of key documents like CIPs, IBs and CRFs
  
  
• Flexible digital workflows for tracking and collaborating on tasks like adverse event reporting or CAPAs
  
  
• Training management to get your staff up-to-date with your latest and greatest SOPs and policies

Check out how one of our customers, UK-based 30 Technology, used Qualio to secure ISO 14155 adherence for their medical device's clinical route to market.

Conclusion

ISO 14155:2020 should play a pivotal role for any company involved in clinical investigations of medical devices, and certification should be a key strategic target for your operation.

By understanding ISO 14155's requirements, aligning your processes, and implementing rigorous oversight with the best digital quality management tools, your company can ensure a clinical investigation process that puts patient safety and rigorous, high-quality data quality front and center.