FDA in late December 2019 recognized the newly revised International Organization for Standardization (ISO) risk management standard for medical devices, ISO 14971:2019, along with more than 100 other consensus standards. However, it will continue to accept declarations of conformity to the previous version ISO 14971:2007, in support of premarket submissions and the changes assimilation can be categorized as follows.
- A change that introduces a new risk or modifies an existing risk that could result in significant harm;
- A change to risk controls to prevent significant harm and;
- A change that significantly affects the clinical functionality or performance specifications of the device.
When applied to software, the above approach would require a premarket submission to the FDA. For a Premarket Approval Application (PMA)-approved SaMD, an auxiliary application would be required for changes that affect safety or effectiveness, such as new indications for use, new clinical effects, or technology modifications that affect performance characteristics.
Premarket approval (PMA) is the regulatory review process conducted by the FDA to evaluate the safety and effectiveness of Class III medical devices. These devices are of substantial importance in preventing impairment of human health or present a potential, unreasonable risk of illness or injury. [2]
FDA Guidance
To overcome the issues and problems with software-controlled medical devices, and to set the standards and regulations for this, the FDA issued its first Software Guidance over 20 years ago. The general FDA regulations for design controls (21 CFR 820.30) apply to all medical device software. This FDA Guidance describes how to interpret the regulations for different aspects of the software. It has developed various guidelines to make more common and consistent rules for software classified under Software as a Medical Device. [3]
- Software as a Medical Device must support clinical vocabulary for its use; this has to do with proper instruction and design in the interface.
- It should address clinical evaluation methods and clinical evidence relevant to the use of the SaMD software.
- It should have various recommendations attached to the software for analytical purposes and those manufacturers should outline potential adverse consequences.
Submission to FDA
The companies intending to manufacture a SaMD must need to submit a marketing application to FDA when they are about to release the device in the market. The changes incorporated in design and developments are reviewed under the 510(k) notification.Some changes may not require a review based on the guidance provided in “Deciding when to submit a 510(k) for a software change to an existing device.” Many modifications to SaMD includes algorithm architecture modifications and re-arrangement with new data sets, which are under the software modifications guidance would be subject to premarket review. [1] The types of principles fall into two broad categories:
Pre-Market:
- Data to establish the evidence on SaMD:
- Scope and intended use/environment of use.
- Safety and Effectiveness
- Specificity/Sensitivity
- Reliability/Limitations/accuracy
Post Market
Continue to create real word data on:
- Performance.
- Complaints.
- Safety
Effectiveness
The Pre-Market process of the 510(k) application includes the following steps :- Confirm your FDA product code, regulation number, and predicate devices.
- Identify all testing, FDA guidance, consensus standards, and clinical data requirements.
- Prepare a detailed gap analysis report to provide a clear pathway for 510(k) submission.
- Compile all the data and submit the application and address the post-submission questions.
PMA is the most precise device marketing application required by the FDA. Applicants must receive FDA approval of their PMA application before marketing the device. FDA approves the application only when the PMA contains valid evidence to ensure that the device is safe and effective for its intended use/uses.
Post-approval studies can provide data of approved medical devices considering safety and effectiveness. This data contains patient’s, health care professionals, the device industry, the FDA and other stakeholders’ information. The FDA has all the rights to perform a post-approval study at the time of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application.
In a nutshell, all the application processes are not open-ended, these include iterative improvements that are mainly focused on obtaining a safe, effective, and exact treatment that can be served with the aid of SaMD. A benchmark performance objective or a predetermined expected level of SaMD is already set, accordingly, the algorithms are indulged and modified. This is accomplished by taking into consideration the algorithm changes protocols. A validation process is pre-determined in such a way that it emphasises safety, effectiveness, and real-world monitoring of performance.
To know more about the SaMD and its details and regulations and submission process of SaMD for approval to EU MDR, please check the below articles:
- Software as a Medical Device (SaMD)
- EU MDR Regulations for SaMD Submission
Reference
[1] Is a new 510(k) required for a modification to the device? | FDA
[2] Premarket Approval (PMA) | FDA
[3] Software as a Medical Device (SAMD): Clinical Evaluation - Guidance for Industry and Food and Drug Administration Staff (fda.gov)
