Eliza Johnson, BS, CRCST, has a strong passion for helping others throughout the health care and medical device industries. She currently works as a quality specialist at ARCH Medical Solutions, where she delves into medical device manufacturing processes, utilizes quality and compliance systems, and completes essential quality system documentation. This role builds upon her 2 years as a CRCST at Exeter Hospital, where she gained experience decontaminating and sterilizing medical devices in preparation for surgical use.

Eliza Johnson, BS, CRCST

Balancing Regulation and Risk of AI and Machine Learning Software in Medical Devices

Artificial intelligence (AI) and machine learning (ML) software have experienced significant growth across various industries, including health care. These developing technologies already have the potential to detect complications caused by infection quickly and accurately. However, integrating these new devices into an established regulatory process has proven challenging. Additionally, there are concerns about trusting devices that produce unpredictable outputs. Due to their distinct characteristics, specific medical devices utilizing AI/ML technology must undergo an adjusted regulatory process to be marketed.

AI-based software within the medical device industry is on the rise, with over 1,015 devices with AI-enabled software authorized for marketing in the US by the FDA as of March 25, 2025.

 Included on the FDA’s AI/ML-Enabled Medical Devices List

 is the Sepsis ImmunoScore. Approved in April 2024, this was the first FDA-authorized AI software designed to aid in the prediction and diagnosis of sepsis.

 The Sepsis ImmunoScore uses AI/ML software to pull inputs that include demographic data, vital signs, and blood culture results from the electronic medical record, enabling the ImmunoScore to output the risk for the presence or development of sepsis for that patient within 24 hours.

In a prospective study published in November 2024, it was explained that the AI algorithm for ImmunoScore was developed through a derivation cohort of patients and was assessed for accuracy on both internal and external cohorts.

 The results of this study concluded that the ImmunoScore had a “high overall diagnostic accuracy for predicting sepsis” and was “highly predictive” of secondary outcomes, including “in-hospital mortality, length of stay, ICU [intensive care unit] admission within 24 hours, use of mechanical ventilation within 24 hours, and use of vasopressors within 24 hours.” The ImmunoScore is just 1 example of AI’s potential to assist health care professionals through informed decision-making. Although the capabilities of these devices seem promising, concerns regarding their trustworthiness must be addressed by regulatory bodies and standardization organizations.

Artificial Intelligence/Machine Learning Software

Understanding the differences among various types of AI software is essential for recognizing the need for heightened regulation of devices that utilize these systems. In its second white paper, the Association for the Advancement of Medical Instrumentation (AAMI)/British Standards Institution (BSI) Initiative on AI provides an overview of AI systems used in the medical device industry.

 This includes rules-based AI, systems that “mimic human behavior-making decisions by applying static rules to arrive at predictable decisions,”

 compared with data-driven machine learning systems that can learn from inputs and make judgments.

 Data-driven ML systems can be further categorized into locked ML models and continuous learning models.

 In locked machine learning models, the algorithms and outputs will not change automatically and require external approval to change,

 whereas continuous learning models can automatically adjust their algorithms and update outputs based on changes.

 From a regulatory perspective, these continuous learning models are the most challenging, as the algorithms may change automatically, making it difficult to predict outcomes.

A significant concern with AI in the medical device industry, particularly with continuous learning models, is trusting these unpredictable systems with tasks that were previously performed by humans, which can pose a risk to patient safety if they fail to perform as expected. The AAMI/BSI Initiative recognizes this unique situation by describing how, in the medical device industry, trust is generally gained not only by an overview of the device’s mechanisms and technologies but also by validating that the device produces “reliable and predictable outputs.”

 This is where concern arises for many: If AI/ML devices can change their outputs after validation, how can they be trusted to produce those reliable and predictable outputs?

Some considerations from AAMI and BSI addressing this concern include that the input data used to train algorithms should be “predefined, relevant, and appropriate” and that performance metrics should be implemented to allow for live monitoring against predicted outputs.

 Guidance from the FDA has also suggested that developers describe anticipated algorithm changes before marketing the device,

 reducing the potential of unknown and unpredictable outputs once in use.

Regulation of AI/ML-based Medical Devices

Just as there are different types of AI technologies, from a regulatory perspective, there are also other types of software that can be used in (or as) medical devices. According to the FDA, the primary types of software within the medical device industry include Software 

 medical devices, and software used in the manufacturing process of a device.

 When AI/ML software is “intended to treat, diagnose, cure, mitigate, or prevent disease or other conditions,” it is considered a medical device and referred to as SaMD by the FDA and International Medical Device Regulators Forum .

Furthermore, medical devices (including SaMD) can be categorized into 3 classes by the FDA. These classifications give insight into the risk the device poses to the patient. For example, a Class I device poses a low risk to the patient, whereas a Class III device poses the greatest risk. The FDA has different premarket submission requirements depending on the device’s classification. If a device is classified as Class I or II, a 510(k) submission is required to market the device (excluding exemptions).

 However, because Class III devices “support or sustain human life, are of substantial importance in preventing impairment of human health, or present a potential, unreasonable risk of illness or injury,”

and pose the highest risk to the patient, these devices require a different type of premarket submission. Class III devices require a premarket approval application (PMA) by the FDA, providing scientific evidence that the device would be safe for use.

The unique capabilities of AI/ML SaMD to adapt and change its algorithms after the PMA process has been completed present new challenges for regulating these devices. In 2019, the FDA released a discussion paper and requested feedback reviewing the process for modifications to AI/ML-based SaMD.

 The paper notes that the FDA expects algorithm changes to be anticipated and described in the premarket submission.

 Additionally, some of these algorithm changes would still require a premarket review.

Based on the feedback provided in response to the request from the discussion paper, the FDA released an action plan for AI/ML SaMD.

 In this action plan, predetermined change control plans (PCCPs) were discussed, specifically, how anticipated and prespecified changes may be captured in a PCCP, which may avoid the need for a new PMA every time an algorithm change occurs.

 This approach can be more efficient, allowing changes to be anticipated and described where a PMA may not be needed. Of course, changes that would pose heightened risk or differ from those described in a PCCP may still require a PMA, as previously noted. The action plan also mentions that “FDA liaisons participate in the standardization efforts of [the AAMI] AI Committee to address the risk management of AI-driven medical devices,”

 and that the FDA is committed to continue working with organizations such as AAMI and BSI to address AI/ML developments.

In 2023, the FDA published a set of guiding principles for PCCPs.

 According to AAMI Array author Eric Henry, as of October 2024, the only AI/ML-specific guidance published by the FDA was the draft guidance for PCCPs.

 In December 2024, the FDA published its final guidance for marketing submission recommendations for PCCPs for AI-enabled devices.

In January 2025, the FDA published an additional draft guidance intended to “[provide] lifecycle management and marketing submission recommendations consistent with a TPLC [Total Product Life Cycle] approach for AI-enabled devices,”

which also references the final guidance for submission recommendations for PCCPs. The FDA requested comments for this draft guidance to be submitted by April 7, 2025.

AI and ML technology have the potential to become an important asset for use in future medical devices. As the use of this technology grows, health care professionals must continue to advocate for the appropriate regulation of these devices. Advocacy for an adjusted regulatory process for these devices enables industry professionals to continually embrace evolving technology while maintaining confidence that these devices are safe and reliable for use.

Artificial intelligence and machine learning (AI/ML)-enabled medical devices. FDA. March 25, 2025. Accessed May 22, 2025. 

https://www.fda.gov/medical-devices/software-medical-device-samd/artificial-intelligence-and-machine-learning-aiml-enabled-medical-devices

Device classification under Section 513(f)(2)(de novo). Updated June 2, 2025. Accessed May 22, 2025. 

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?id=DEN230036

Bhargava A, López-Espina C, Schmalz L, et al. FDA-authorized AI/ML tool for sepsis prediction: development and validation. 

Machine Learning AI in Medical Devices: Adapting Regulatory Frameworks and Standards to Ensure Safety and Performance

Reddy S. Global harmonization of artificial intelligence-enabled software as a medical device regulation: addressing challenges and unifying standards. 

. 2024;3(1):100191. doi:10.1016/j.mcpdig.2024.100191

Software as a Medical Device (SAMD). FDA. December 4, 2018. Accessed May 22, 2025. 

https://www.fda.gov/medical-devices/digital-health-center-excellence/software-medical-device-samd

Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD)

https://www.fda.gov/media/122535/download?attachment

Classify your medical device. FDA. February 7, 2020. Accessed May 22, 2025. 

https://www.fda.gov/medical-devices/overview-device-regulation/classify-your-medical-device

Premarket approval (PMA). FDA. May 16, 2019. Accessed May 22, 2025. 

https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/premarket-approval-pma

Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD) Action Plan

https://www.fda.gov/media/145022/download?attachment

Henry E. AI/ML in medical devices: US & EU regulatory perspectives. AAMI

October 23, 2024. Accessed May 22, 2025. 

https://array.aami.org/content/news/ai-ml-medical-devices-us-eu-regulatory-perspectives

Predetermined change control plans for machine learning-enabled medical devices: guiding principles. FDA. December 3, 2024. Accessed May 22, 2025. 

https://www.fda.gov/medical-devices/software-medical-device-samd/predetermined-change-control-plans-machine-learning-enabled-medical-devices-guiding-principles

Marketing submission recommendations for a predetermined change control plan for artificial intelligence-enabled device software functions. FDA. December 3, 2024. Accessed May 22, 2025. 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/marketing-submission-recommendations-predetermined-change-control-plan-artificial-intelligence

Artificial intelligence-enabled device software functions: lifecycle management and marketing submission recommendations. FDA. January 7, 2025. Accessed May 22, 2025. 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/artificial-intelligence-enabled-device-software-functions-lifecycle-management-and-marketing

Artificial intelligence-enabled device software functions: lifecycle management and marketing submission recommendations; draft guidance for industry and food and drug administration staff; availability. 

https://www.federalregister.gov/documents/2025/01/07/2024-31543/artificial-intelligence-enabled-device-software-functions-lifecycle-management-and-marketing

Articles

Artificial intelligence may be revolutionizing sepsis detection and diagnosis, but can we trust it without strong regulatory guardrails? As AI/ML-enabled medical devices rapidly evolve, IPs must stay informed and involved to ensure safety keeps pace with innovation. Let’s take a closer look at how to advocate for innovative safe implementation.

Creutzfeldt-Jakob Disease Case Showing Severe Loss of Granular and Purkinje Cells with Active Microglia

Creutzfeldt-Jakob disease (CJD) is a widely recognized disease among medical device industry professionals that poses unique challenges for instrument reprocessing. Although care must be taken with all medical instruments, exceptional care must be taken with instruments potentially infected with CJD to ensure they are correctly disposed of or are safe for reuse. Generally, the safest and most accepted method for dealing with instruments contaminated with CJD is incineration.

However, incineration is only sometimes practical. Therefore, decontamination guidelines have been provided by the CDC and the World Health Organization (WHO) and are also addressed by the Association for the Advancement of Medical Instrumentation (AAMI). Many factors must be considered when choosing instruments in preparation for a surgical procedure on a patient with CJD. In the same way, departments that handle surgical instruments must consider unknown cases of CJD and how to handle instruments that could be potentially infected with CJD.

Before examining the disposal and decontamination guidelines for instruments confirmed to be infected or potentially infected with CJD, it is essential to understand the biological structure and impact of the disease. CJD is a type of prion disease, or a transmissible spongiform encephalopathy (TSE), that can cause abnormal folding of proteins in the body.

 This abnormal folding can lead to symptoms that progress rapidly and can often include dementia,3 unsteadiness and clumsiness,

 and other neurological symptoms. CJD is a progressive and fatal brain disorder that has no treatment to stop the progression of symptoms or to eliminate the disease.3

According to the WHO, human TSEs (including CJD) have been caused by “exposure to infectious material through the use of human cadaveric-derived pituitary hormones, dural and cornea homografts, and contaminated neurosurgical instruments.”

 Certain infections have been tied to distinctive types of CJD.

There are 3 primary forms of CJD: sporadic, genetic (familial), and acquired (can include iatrogenic).

 Sporadic CJD is the most common form, accounting for 85% of reported cases.5 Sporadic cases of CJD occur when proteins already present in the body fold abnormally for an unknown reason.

 Genetic (or familial) CJD occurs when genetic mutations are inherited from a family member with CJD.6 Iatrogenic cases are acquired in health care settings through contact with prions that can come from contaminated medical instrumentation.

 Due to this, guidelines for disposing and reprocessing medical instruments that have been potentially contaminated have been shared by the CDC and WHO and are included in ANSI/AAMI ST79:2017: Comprehensive Guide to Steam Sterilization and Sterility Assurance in Health Care Facilities.

Notably, a variant form of CJD (considered acquired

), also known as vCJD, is classified as a bovine spongiform encephalopathy (BSE),

 a type of TSE that affects cows. Although similar in name to CJD, human infections of vCJD have primarily been attributed to the consumption of animal products from BSE-infected cows.

 Because of this, most available research on instrument decontamination has been reviewed for classic CJD. However, WHO guidelines specify that instruments used for patients with confirmed or suspected cases of vCJD shall be decontaminated following the guidance listed in the WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies,

 which also includes guidance for classic CJD.

Prion Resistance to Decontamination and Sterilization

Instruments confirmed to be infected with CJD and instruments potentially infected with CJD must be treated differently from standard instrumentation as this type of disease resists common decontamination and sterilization practices.

Incineration or Reprocessing of Instrumentation

Due to CJD’s resistance to standard reprocessing protocols, the CDC and WHO recommend incinerating instruments exposed to high-infectivity tissues.

 High-infectivity tissues are those of the central nervous system, including the brain, spinal cord, and eyes.

 The CDC and WHO have also discussed methods for instruments that are not incinerated.

It should be noted that all methods detailed below should be followed by cleaning the instruments, rinsing them in water, and subjecting them to routine sterilization.

 According to the WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies, heat-resistant instruments may be immersed in sodium hydroxide (NaOH) and run through a gravity displacement autoclave at 121 °C for 30 minutes.

 The WHO lists recommendations for heat-resistant instruments, starting with the most severe treatments. Aside from incineration, the NaOH/gravity displacement autoclave method is considered the most severe treatment.

Another method cited by the WHO and CDC suggests immersing instruments in 1N NaOH or sodium hypochlorite for an hour, transferring them to water, and heating them in a gravity displacement autoclave at 121 °C for an hour.

 The last method cited by the CDC that aligns with WHO recommendations is to immerse the instruments in NaOH or sodium hypochlorite for an hour, remove and rinse in water, transfer to an open pan, and either heat in a gravity displacement autoclave at 121 °C or a porous load autoclave at 134°C for an hour.

The least severe treatment in the WHO recommendations for heat-resistant instruments is autoclaving at 134 °C for 18 minutes.

Of course, not all instruments used in a surgical procedure are heat resistant. For instruments that are heat sensitive, the CDC suggests, “heat-sensitive reusable instruments…should be decontaminated. This can be done by flooding with or soaking in 2N NaOH or undiluted sodium hypochlorite for 1 hour. They should [then] be rinsed with water,” which aligns with WHO recommendations.

 Care must be taken during these processes to ensure the safety of staff handling the contaminated instruments and chemical agents.

While there are circumstances in which the previous methods may be appropriate, certain challenges related to instrument composition, practicality, and the safety of reprocessing professionals must be considered. In its guidance, the WHO states that hypochlorite can be corrosive to stainless steel instruments and should not be used to soak instruments while in an autoclave, as this could cause corrosion in the autoclave itself.

 Hypochlorite also poses a potential respiratory hazard if the process is not conducted in a properly ventilated location.

 The CDC recommends that when instrument composition and chemical intolerances are unclear, the manufacturer should be consulted.

 In this scenario, the instrument’s instructions for use (IFU) could also be a useful reference. In addition, staff should always wear proper protective equipment when they are in contact with CJD and the chemical agents used in these procedures.

As mentioned, understanding how to handle instruments potentially infected with CJD is essential to ensure the safety of all reprocessing staff. The WHO recognizes that it is impractical for every instrument used on an individual potentially infected with CJD to be unnecessarily incinerated, so instruments may be quarantined until suspected cases have been confirmed.

However, this raises a question for many industry professionals: What is considered a potentially infected instrument? Not all CJD cases may be suspected during a surgical procedure. Do all instruments used on high-infectivity tissues (eg, the brain, spinal cord, and eyes) have the potential to be infected with CJD if an individual was not tested before surgery?

The CDC touches on this topic in its guidance by stating, “[if] it’s not yet known if a patient undergoing neurosurgery has CJD (or another prion disease)…instruments involved in these procedures should be reprocessed as if the patient has suspected or confirmed CJD.”

Reprocessing all high-infectivity tissue instrumentation as if infected with CJD seems to be the safest method to avoid prion contamination, but how many reprocessing facilities comply with this guidance? Is this guidance practical for all health care facilities? Aligning recommendations and elaborating on this topic between WHO, CDC, ANSI/AAMI, and even the manufacturers’ IFUs would greatly benefit reprocessing staff to comply with best practices.

CJD’s resistance to standard decontamination protocols presents unique challenges for reprocessing staff. While incineration is generally the preferred method for managing instruments potentially infected with CJD, this is not always practical. To address this, decontamination guidance has been shared by the CDC, WHO, and ANSI/AAMI ST79:2017 for instruments that cannot be incinerated.

Unknown cases of CJD present yet another challenge when managing instrumentation. Continued advocacy from professionals in the medical device industry is essential to clarify best practices for unknown cases of CJD and promote the alignment of current recommendations.

Infection control for CJD. CDC. May 13, 2024. Accessed December 9, 2024. 

https://www.cdc.gov/creutzfeldt-jakob/hcp/infection-control/index.html

WHO infection control guidelines for transmissible spongiform encephalopathies: report of a WHO consultation, Geneva, Switzerland, 23-26 March 1999. World Health Organization. Accessed December 9, 2024. 

Clinical overview of Creutzfeldt-Jakob disease (CJD). CDC. May 13, 2024. Accessed December 9, 2024. 

https://www.cdc.gov/creutzfeldt-jakob/hcp/clinical-overview/index.html

Prion diseases are a group of rare, neurodegenerative brain disorders. CJD Foundation. Accessed December 9, 2024. 

https://cjdfoundation.org/types-of-prion-disease/#acquired

Classic Creutzfeldt-Jakob disease. CDC. May 13, 2024. Accessed December 9, 2024. 

https://www.cdc.gov/creutzfeldt-jakob/about/index.html

CJD diagnostic criteria. CDC. May 13, 2024. Accessed December 9, 2024. 

https://www.cdc.gov/creutzfeldt-jakob/hcp/clinical-overview/diagnosis.html

Asked & answered: device disposal. Association for the Advancement of Medical Instrumentation. March 1, 2020. Accessed December 9, 2024. 

https://array.aami.org/content/news/asked-answered-device-disposal

ANSI/AAMI ST79:2017 with amendments A1:2020, A2:2020, A3:2020, A4:2020: comprehensive guide to steam sterilization and sterility assurance in health care facilities. Association for the Advancement of Medical Instrumentation. Accessed December 9, 2024. 

https://aami.org/standards/featured-standards/ansi-aami-st79

Clinical overview of variant Creutzfeldt-Jakob disease. CDC. November 12, 2024. Accessed December 9, 2024. 

https://www.cdc.gov/variant-creutzfeldt-jakob/hcp/clinical-overview/index.html

About prion diseases. CDC. April 22, 2024. Accessed December 9, 2024. 

https://www.cdc.gov/prions/about/index.html

Creutzfeldt-Jakob Disease (CJD) presents significant challenges for infection control. Learn best practices for safe instrument disposal, reprocessing, and compliance with CDC and WHO guidelines.

Ensuring Safe Practices: Managing Surgical Instruments in the Context of Creutzfeldt-Jakob Disease

(Adobe Stock 345854096 by MQ-Illustrations)

Environmental hygiene must be considered when determining the layout of a health care facility. Structural features such as ventilation systems and air pressure regulation are critical aspects that can control the spread of numerous pathogenic airborne diseases. Pressure differences can prevent contaminated air from traveling to high-risk areas with vulnerable and immunocompromised patients. Regulation of air through pressure differences is essential in health care facilities to promote a safe patient environment.

One pathogenic microorganism that must be considered for ventilation in a health care facility is 

), an airborne disease that can be spread through droplet nuclei.

 particles range from 1 to 5 microns in size and can last in the air for several hours.

 Due to their size and ability to survive in the air for extended periods, 

 particles can be hazardous to immunocompromised patients. In the 2023 Global Tuberculosis Report by the World Health Organization, it was noted that 

 was the leading cause of death for people diagnosed with HIV.

 Therefore, it is important to regulate air pressure within facilities to prevent 

 patients from spreading the disease throughout the hospital while protecting them from other airborne diseases.

 is not the only pathogen that can travel and remain in the air for an extended period. COVID-19 is a viral airborne infectious pathogen that can remain in the air for hours.

 Although many controls have been implemented to reduce the impacts of COVID-19, one necessary mitigation is utilizing air pressure and ventilation systems. The central concept behind using air pressure to aid in environmental hygiene is to move air in a clean-to-less-clean direction.

 This strategy applies not only to COVID-19 but also to 

 and other airborne diseases that travel throughout health care facilities.

Pressure differentials between rooms can help move air from clean to less clean areas. Controlling the pressure within these rooms can be accomplished using a heating, ventilation, and air conditioning system. When a positively pressurized room is adjacent to a negatively pressurized room, the air will flow from positive to negative. The American Society for Healthcare Engineering (ASHE) distinguishes between positive and negative pressurized rooms by stating, “Positively pressurized rooms are usually designed to protect a patient, clean supplies, or equipment within the room. Negative pressure is used to contain airborne contaminants within a room”.

 Understanding which rooms will contain infected patients and surgical instruments in contrast to which rooms will contain immunocompromised patients is crucial for patient safety.

Regulation of air pressure is essential in sterile processing departments because this is where reusable surgical instrumentation and medical devices are reprocessed between patient use. It is critical to separate the decontamination side of the department from the assembling and sterilization areas to avoid contaminating disinfected and sterilized instrumentation. Although these department areas are generally divided, most departments will have a passthrough window for specific pieces of instrumentation that would be damaged in a washer-disinfector, such as specific fiberoptic instruments. However, because this also allows airflow between the 2 areas, it is also critical to have air pressure regulations between them. ASHE recommends that the clean side of a sterile processing department (SPD) is positively pressured, whereas the decontamination side of the SPD is negatively pressured,

ASHE guidelines recommend that operating rooms stay in a state of positive pressure.

 This ensures that potentially infectious air from the surrounding hallways does not flow into the operating room, where immunocompromised patients could be particularly vulnerable to infection. In exceptional cases where patients infected with airborne diseases (such as 

) need emergency surgery, additional environmental hygiene measures must be implemented. Since operating rooms are generally positively pressured, there is potential for airborne diseases from infected patients to travel from the operating room to adjacent corridors. Measures such as portable HEPA filters and redirecting airflow to the outside environment are often considered to prevent this.

 As discussed previously, environmental hygiene needs to be a priority within the varying rooms of a health care facility to protect not only infected patients from spreading diseases but also immunocompromised patients from contracting diseases.

Regulating air pressure within health care facilities is critical to managing the airborne transmission of tuberculosis, COVID-19, and other pathogenic diseases. These diseases and other airborne pathogens can critically impact patients and pose a risk to everyone in a healthcare facility. Due to their size and ability to remain in the air for extended periods, redirecting airflow is essential to lower the risk of infection throughout the facility. Prioritizing environmental hygiene measures contributes to a safe environment for all patients.

. Published December 21, 2023. CDC. Accessed July 25, 2024. 

https://www.cdc.gov/infection-control/hcp/environmental-control/air.html#

Clinical overview of tuberculosis. Tuberculosis (TB). CDC. Published May 8, 2024. 

https://www.cdc.gov/tb/hcp/clinical-overview/index.html#

Global Tuberculosis Report 2023. World Health Organization. 

https://cdn.who.int/media/docs/default-source/hq-tuberculosis/global-tuberculosis-report-2023/global-tb-report-2023-factsheet.pdf?sfvrsn=f0dfc8a4_4&download=true

Indoor air and coronavirus (COVID-19). US Environmental Protection Agency. Published May 6, 2024. 

https://www.epa.gov/indoor-air-quality-iaq/indoor-air-and-coronavirus-covid-19#:~:text=Transmission%20of%20COVID%2D19%20from,for%20hours%20in%20some%20cases

Community, work, and school. CDC. Published February 11, 2020. 

https://www.cdc.gov/coronavirus/2019-ncov/community/ventilation.html

Barrick JR, Holdaway RG. Mechanical Systems Handbook for Health Care Facilities. ASHE; 2014. 

https://www.ashe.org/compliance/ec_02_05_01/01/roompressurization


Learn more about how effective air pressure regulation in health care facilities is crucial for controlling airborne pathogens like tuberculosis and COVID-19, ensuring a safer environment for all patients and staff.

Environmental Hygiene: Air Pressure and Ventilation: Negative vs Positive Pressure

The US Federal Drug Administration (FDA) and the International Organization for Standardization (ISO) play significant roles in the production of medical devices currently on the market. One area covered by both the FDA and ISO is 

 to uphold the Federal Food, Drug, and Cosmetic Act (FD&C Act) through quality system regulation.

 ISO is an international organization that creates standards based on input from experts in different industries.

 One standard that is widely recognized throughout the medical device manufacturing industry is 

. Professionals within this industry must understand the current requirements of the FDA and ISO 13485 to have a high-functioning, well-regulated quality system.

For companies that manufacture finished medical devices, implementing the regulations required by 21 CFR Part 820 allows these facilities to be compliant with the FD&C Act. 21 CFR Part 820 sets forth CGMP (current good manufacturing practices) for the regulation of facilities that partake in the manufacture or related practices for finished medical devices that are “manufactured, imported, or offered for import in any State or Territory of the US, the District of Columbia, or the Commonwealth of Puerto Rico.”

 This regulation takes place through a quality management system (QMS). Since a federal agency puts this regulation in place, facilities participating in the previously stated activities must comply with these requirements.

One of the main differences between the FDA and ISO is that ISO is a nongovernmental organization. ISO 13485 is an international standard that also sets forth principles managed by a QMS for facilities involved in the manufacture of medical devices. Although this means that registration for ISO 13485 certification is not currently required by law in the US, this is a highly recognized global standard. 

Since this is a globally recognized standard, this certification also considers some of the regulatory requirements from the European Union (EU), such as EU-MDR (Medical Devices Regulation) and EU-IVDR (In-Vitro Diagnostic Medical Devices Regulation).

 Although adhering to ISO 13485 in the US is currently optional for medical device manufacturers, companies that export their devices to other countries may find that registration to ISO 13485 is required.

 Within the next 2 years, the FDA has announced proposed changes to the necessity of adhering to ISO 13485 requirements.

Effective February 2, 2026, 21 CFR 820 will be amended to include ISO 13485 standards by reference.

 The FDA aims to revise its requirements in 21 CFR 820 by aligning the regulations with ISO 13485 standards in an amended Quality Management System Regulation (QMSR). This process is called a “harmonization”

 of the 2 requirements. The main takeaway from aligning the 2 is that this will provide timelier access to new finished devices with additional cost savings throughout the industry.

 In addition to cost savings, “The qualitative benefits of the rule include quicker access to newly developed medical devices for patients leading to improved quality of life of the consumers.”

 Although the benefits of this harmonization were stated, the anticipated addition of ISO 13485 to the amended QMSR has brought about some concerns from professionals within the medical device industry.

Although the management of quality systems according to FDA registration and ISO certification are similar, the 2 have some differences, including specific terminology. To address this, the FDA reviewed timely public comments regarding concerns with the alignment of the standard and the current regulation. 

One general comment requested that the FDA consider adding the term “correction,” as defined in ISO 13485.

 In the ruling, the FDA agreed with this commenter that adding this term would further align the QMSR with ISO 13485. The FDA also reiterated that modifications will be implemented to allow the QMSR to be consistent throughout.

 It is important to note that there are requirements in the current 21 CFR 820 regulation not included in ISO 13485 that companies must meet to comply with the FD&C Act. This will remain true in the updated QMSR.

It is recommended that medical device professionals become familiar with the requirements of the ISO 13485 standard before their anticipated implementation within the next 2 years. Understanding the FDA’s 21 CFR 820 regulations and the current ISO 13485 standard allows companies to prepare for the QMSR transition. 

Introducing new requirements to a quality management system may include some concerns. However, it is important to remember that improvement within a quality system is essential for managing the production of safe, high-quality devices.

21 CFR Part 820 -- Quality system regulation. Accessed August 29, 2024. 

https://www.ecfr.gov/current/title-21/chapter-I/subchapter-H/part-820

ISO. Accessed August 29, 2024. About ISO. 

Medical devices; quality system regulation amendments. Federal Register. Published February 2, 2024. Accessed August 29, 2024. 

https://www.federalregister.gov/d/2024-01709

BSI. ISO 13485 Frequently asked questions. 2024. Accessed August 29, 2024. 

https://www.bsigroup.com/siteassets/pdf/en/insights-and-media/insights/brochures/bsi-md-iso-13485-faqs-en-gb.pdf


The FDA's 21 CFR Part 820 and ISO 13485 are crucial in regulating medical device quality systems. Harmonizing these standards by 2026 will streamline compliance, improve patient access to devices, and align US regulations with global practices.

Eliza Johnson, BS, CRCST

Articles

Balancing Regulation and Risk of AI and Machine Learning Software in Medical Devices

Ensuring Safe Practices: Managing Surgical Instruments in the Context of Creutzfeldt-Jakob Disease

Environmental Hygiene: Air Pressure and Ventilation: Negative vs Positive Pressure

Implementing FDA 21 CFR Part 820 & ISO 13485 on Quality System Regulation

Enhancing Infection Prevention in Medical Devices Through Quality Systems