GP-026 Product requirements for US market
Purpose
This procedure outlines the steps and requirements for obtaining FDA approval for the medical device we develop and for initiating its commercialization in the United States, ensuring compliance with FDA regulations, ISO 13485, and internal quality management system (QMS) processes.
Scope
This procedure applies to the medical devices we develop and we aim to place in the US market. This procedure applies to all personnel involved in the regulatory submission, approval process, and subsequent activities required to market the medical device in the US.
Definitions
- FDA: Food and Drug Administration
- QMS: Quality Management system
- UDI: Unique Device Identifier
- IFU: Instructions for Use
- US Agent: A representative for regulatory correspondence in the US, required for foreign companies entering the US market
- PMS: Post-market surveillance
- GUDID: Global Unique Device Identification Database
- UDI: Unique Device Identifier
- DI: Device Identifier
- PI: Production Identifier
- PCCP: Predetermined Change Control Plan
Responsibilities
JD-005
To accomplish legal compliance and all the regulatory requirements of the medical devices.
JD-004
To ensure all the documents and records that guarantee the medical devices regulatory requirements compliance are documented and stored according to our GP-001 Control of documents
.
JD-003
To organize and manage development resources to achieve compliance with applicable requirements.
JD-001
To approve the procedure and provide the required resources to perform the activities described on it.
Inputs
- Applicable FDA requirements
Outputs
- Technical files in accordance with all the applicable requirements
- Applicable regulatory FDA approval
- Placing on the market our products in accordance with all the applicable legal requirements
Development
Pre-submission activities
The pre-submission phase is critical for planning and preparing the necessary documentation, strategy, and interactions required to facilitate the FDA regulatory submission process. This section outlines the key activities and considerations before formally submitting our application to FDA.
Device classification and predicate device identification
The first step to start gathering applicable requirements and planning the necessary documentation for submission is the determination of the classification of the medical device.
Device classification is based on the intended use and indications for use. In addition, the classification is risk based: the risk the device poses to the patient and/or users determines the class of the device.
FDA defines three classes of medical devices: class I, class II, class III, where class I includes all those devices with the lowest risk and class III includes all those devices with the greatest risk.
Useful starting points for device classification definition are
Once the classification is established, the following step is to identify any legally marketed devices that are similar to the device we aim to certify in terms of intended use and technological characteristics to demonstrate substantial equivalence.
These devices, similar in intended use and technology, are called predicate devices
.
This step is only applicable to class II devices.
In order to select the most appropriate predicate device to claim equivalence with, it is recommended to follow the dedicated FDA guidance: The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications.
Regulatory strategy definition
According to the ouputs of the previous steps (device classification, predicate device identification), we can determine the most appropriate regulatory pathway for FDA submission.
The available pathways are the following:
- 510(k): this pathway shall be chosen when the device has a low-medium risk profile (class II devices) and when a predicate device is available in the US market.
- De Novo: this pathway shall be chosen when the device has a low-medium risk profile (class II devices) and no predicate devices are available in the US market.
- Premarket approval (PMA): this pathway shall be chosen when the device has a high risk profile (class III).
When the most appropriate regulatory pathway is selected, it is possible to map out all the FDA requirements applicable to the device in order to prepare the technical documentation for the submission, as detailed in the following secction.
As part of the regulatory strategy, we will consider an option that FDA gives to manufacturer of medical devices to get insights and clarification on the submission: the pre-submission meeting.
A pre-submission meeting with the FDA is an optional but highly valuable step that allows us to engage in a collaborative discussion with the FDA before formally submitting our application. During this meeting, we can present our proposed regulatory strategy, technical documentation, and specific questions or challenges related to the submission. The FDA provides non-binding feedback, which can help clarify regulatory expectations, reduce uncertainties, and ensure the submission aligns with applicable requirements.
In order to organise the pre-submission meeting with FDA, we shall prepare the so called pre-submission package
according to the template T-026-001 Pre-submission meeting request
to provide FDA with the necessary information about our medical device and our regulatory strategy to receive FDA clarifications and inputs.
More information about the pre-submission meeting is provided in the dedicated FDA guidance.
Submission preparation
The preparation phase is pivotal to compiling a complete and accurate submission to the FDA. This section describes the steps required to assemble technical documentation, address regulatory requirements, and ensure readiness for submission.
Technical documentation
In order to fulfil applicable FDA requiments, the following main documentation shall be prepared and sent to the FDA for getting device approval:
- Device description: descriptive information of the device, including a description of the technological characteristics, intended use, indications for use, a description of the principle of operation for achieving the intended effect and the proposed conditions of use, inputs, outputs, significant features. If the regulatory pathway is the 510(k), the device description shall contain a reference to the selected predicate device and a description of it, including a comparison to highlight the equivalence between devices.
- Software documentation: it shall include software requirements, specifications, software architecture description, software lifecycle development plan, software verification and validation, any unresolved software anomalies, documented traceability between requirements, verification and validation activities, software risks. The software documentation is generated by following the design process described in the procedure
GP-012 Design, Redesign and Development
. - Risk management documentation: it shall include the risk management plan of the device, risk management analysis demonstrating that risks have been properly mitigated, and a risk management report with discussion of residual risks and an analysis of the benefits-risks profiele of the device. These records are generated by following the process described in the procedure
GP-013 Risk management
. - Cybersecurity documentation: it shall include cybersecurity management plan, security requirements, security architectural design, security risk evaluation and mitigation, penetraton test plan and report. Cybersecurity records are generated by following the process described in the procedure
GP-024 Cybersecurity
. - Human factors and usability engineering documentation: it shall include a summary of data generated by the execution of usability studies to demonstrate the device's safe and effective use by the intended users. The usability records are generated according to the procedure
GP-012 Design, Redesign and Development
. - Clinical evidence documentation: it shall include a summary of the study protocols, results and conclusions to support the proposed claims for the device. These records are generated by following the process described in the procedure
GP-015 Clinical evaluation
. - Labeling documentation: it shall include device label, intended use statement, warnings, precautions, contraindications, IFU.
- Predetermined change control plan (PCCP) documentation: it is a proactive approach to managing changes to the device once approved and placed in the market. The PCCP is documented in the
T-012-020 Predetermined change control plan
, according to the procedureSP-012-003 Predetermined chnage control plan
.
A list of useful FDA guidances to take into considerations when preparing the technical documentation is provided below:
- Content of Premarket Submissions for Device Software Functions
- Guidance on Medical Device Patient Labeling
- Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions
- Design Considerations and Pre-market Submission Recommendations for Interoperable Medical Devices
- Recommended Content and Format of Non-Clinical Bench Performance Testing Information in Premarket Submissions
- Applying Human Factors and Usability Engineering to Medical Devices
- Content of Human Factors Information in Medical Device Marketing Submissions
- Marketing Submission Recommendations for a Predetermined Change Control Plan for Artificial Intelligence-Enabled Device Software Functions
Other documentation required for the submission
In addition to the technical documentation, a few more documents shall be prepared for the submission:
- Administrative documentation: administrative forms applicable to the submission, including a general summary of the submission, executive summary.
- Cover letter: this document shall summarise the purpose of the submission and include all administrative details.
- Truthful and accuracy statement: a template is provided in this FDA webpage.
Fee payment and submission of documents
This section outlines the process for formally submitting the necessary documents to the FDA and paying the applicable user fees.
Fee payment
Before the submission of the required documents to the FDA, we shall pay the applicable fee depending on the type of regulatory pathway chosed for the premarket submission (510(k), De Novo, PMA).
Instructions on how to pay the applicable fee are provided in this FDA webpage.
Upon successfull payment, we will be asked to attached the payment confirmation as part of the submission.
Submission of documents
The FDA has created the option of sending the required documents for premarket submission electronically: the FDA eSubmitter tool. Detailed instructions on how to submit the required documents by means of the FDA eSubmitter tool are provided in the dedicated FDA guidance.
This tool also allows us to track the status of the submission.
Upon successfull submission, we will receive a confirmation receipt from the FDA, including the submission tracking number.
Post-approval activities
Post-approval activities encompass the responsibilities and actions required after the FDA grants market clearance or approval for the medical device.
Device listing and US agent appointment
After FDA approval, the medical device shall be registered in the FDA's database via the FDA Unified Registration and Listing System (FURLS).
The registration of the medical device in the FDA's database is associated with annual renewal fee. More details on the process for registering our medical device and for paying the applicable fee are provided in the dedicated FDA webpage.
It is our responsibility to update the information provided in the FDA's database any time there is a change in the device's information submitted.
Since we are a non-US manufacturer, we have to appoint a US agent to act as a primary contact with FDA for all regulatory and compliance matters. The US agent shall be based in US and shall act as a liaison between us and the FDA. The main responsibilities of the US agent are
- Ensur timely communication and response to FDA inquiries,notifications or administrative requests;
- Assist FDA in scheduling and facilitating facility inspections;
- Notify FDA of any significant changes.
UDI assignment and GUDID database
The Unique Device Identification (UDI) system is a critical component of post-approval compliance. It enhances device traceability, promotes patient safety, and facilitates more efficient post-market surveillance. The UDI assignment process and submission to the Global Unique Device Identification Database (GUDID) are essential steps following FDA approval.
A UDI is composed of a device identifier (DI) and a production identifier (PI). Only FDA-accredited issuing agencies can can provide us with UDI, as further explained in the FDA guidance Unique Device Identification System: Form and Content of the Unique Device Identifie (UDI).
Once the UDI is issued, we are responsible to include it as part of the device labeling and we must provide it through either of the following:
- An easily readable plain-text statement displayed whenever the software is started
- An easily readable plain-text statement displayed through a menu command.
The following step is to register in the Global Unique Device Identification Database (GUDID) and submit the UDI information of our device for traceability purposes.
Whenever there is a change in the information submited to the GUDID, we are responsible to update it.
More information about the GUDID process registration and requirements are provided in the dedicated guidance: Global Unique Device Identification Database (GUDID).
Post-market surveillance activities
Post-market surveillance (PMS) is a critical activity to ensure that the device continues to perform safely and effectively once it is marketed and used in real-world settings.
Once the FDA approval is obtained, we will analyse in details the applicable requirements for post-market surveillance activities, including medical device reporting (described in 21 CFR Part 803
) and customer complaints handling (described in 21 CFR Part 820.198
).
The process to follow will be described in this procedure, together with resposnibilities and timelines, before placing our medical device in the US market.
Associated documents
T-026-001 Pre-submission meeting request
T-012-020 Predetermined change control plan
SP-012-003 Predetermined change control plan
Signature meaning
The signatures for the approval process of this document can be found in the verified commits at the repository for the QMS. As a reference, the team members who are expected to participate in this document and their roles in the approval process, as defined in Annex I Responsibility Matrix
of the GP-001
, are:
- Author: Team members involved
- Reviewer: JD-003, JD-004
- Approver: JD-001