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Rimsys Announces Rimsys AI to Eliminate Repetitive Tasks and Enhance Decision-Making for MedTech Regulatory Teams
Rimsys, the leading Regulatory Information Management (RIM) platform for the MedTech industry, today announced the launch of Rimsys AI, a suite of embedded artificial intelligence (AI) agents.
The beginner's guide to the FDA De Novo classification process
This article is an excerpt from The beginner's guide to the FDA De Novo classification process ebook.
Contents
- Introduction
- Chapter 1: What is an FDA De Novo request?
- Chapter 2: Contents of a De Novo request
- Chapter 3: Submitting a De Novo request
- Appendix A: Acceptance review checklist
Congratulations, you have successfully developed a new medical device! Now you need to take it to market. Normally in the United States this would mean completing a 510(k) submission. However, the 510(k) relies on “substantial equivalence”—a comparison to a similar device already on the market (also called a predicate device) to assess the risk profile of the new device. What if your device is totally new, and there isn’t a similar device to compare it to? Enter the FDA De Novo process. The De Novo process provides a pathway to market for novel devices with a low to medium risk profile.
What does De Novo mean?
According to the Merriman-Webster dictionary, de novo is a Latin word meaning “as if for the first time; or anew.” Perfectly fitting that the FDA uses this term “De Novo” to describe market approval requests for new medical devices or technology where there is no comparable predicate device on the market.
The Food and Drug Administration Modernization Act of 1996 provided the FDA with the authority to create the De Novo Classification Process. It's a process that uses a risk-based strategy for a new, novel kind of medical device, in vitro diagnostic, or medical software solution whose type has previously not been identified and/or classified. It’s a process by which a novel medical device can be classified as a Class I or Class II device, instead of being automatically classified as Class III, which may not be appropriate. Before the implementation of the De Novo process in 1997, all the “not substantially equivalent” (NSE) products were required to be initially classified as a Class III device. But for a lot of devices, this risk class didn’t really make sense. The De Novo process provides a pathway for more accurate classifications of novel, lower-risk devices.
October, 2021, the FDA released a final guidance document "De Novo Classification Process (Evaluation of Automatic Class III Designation)" to provide guidance to the requester (also known as the manufacturer) and the FDA on the process for the submission and review of a De Novo Classification Request under section 513(f)(2) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act). This process provides a pathway to an initial Class I or Class II risk classification for medical devices for which general controls or general and special controls, provide a reasonable assurance of safety and effectiveness, but for which there is no legally marketed predicate device. This guidance document replaced the "New Section 513(f)(2) – Evaluation of Automatic Class III Designation, Guidance for Industry and CDRH Staff" document, dated February 19, 1998.
Consistent with the final rule, the FDA updated the guidance documents below to provide recommendations for submitting De Novo requests, as well as criteria and procedures for accepting, withdrawing, reviewing, and making decisions on De Novo requests, effective January 3, 2022.
- User Fees and Refunds for De Novo Classification Requests
- FDA and Industry Actions on De Novo Classification Requests: Effect on FDA Review clock and Goals
- Acceptance Review for De Novo Classification Requests
The 510(k) and the De Novo processes are similar in that they are both pathways to market for medical devices with low to moderate risk, which is Class I and Class II. The biggest difference between the two is that the 510(k) heavily relies on the concept of "substantial equivalence" to an existing medical device. You must prove this to get the clearance of your 510(k) submission. In the De Novo process, there isn’t a product currently on the market that is “substantially equivalent” to yours, so it’s like starting with a clean slate. For more on the 510(k) process, see our Beginner’s Guide to the 510(k) ebook.
A result of the De Novo process to be aware of is that a successful submission will lead to a new predicate device type that someone else can reference to bring their product to market through the 510(k) process. You’ve done all the work, so now it’s available for anyone to use to provide "substantial equivalence".
De Novo history/timeline
Preparing a De Novo request
1. Do your research! Be sure to complete all the necessary research prior to your submission. You want to be sure that your device is not substantially equivalent to an existing device. Resources to review include:
- The Center for Devices and Radiological Health (CDRH)
- U.S. FDA Device Classification Database
- Device Classification Under Section 513(f)(2)(De Novo)
2. A De Novo request can be submitted with or without a preceding 510(k). There are two options for when you can submit a De Novo request:
Option A: After receiving a not substantially equivalent (NSE) determination (that is, no predicate, new intended use, or different technological characteristics that raise different questions of safety and effectiveness) in response to a 510(k) submission.
Option B: If you’ve determined, after extensive research, that there is no legally marketed device on which to base a determination of substantial equivalence.
3. Be sure all fees are paid to the FDA in advance of submitting a De Novo request. The FDA’s fiscal year begins in October and runs through the following September. Fees have increased each year since they were introduced, but the FDA’s percentage of reviews completed within the 150-day window has increased as well.
A business that is qualified and certified as a “small business” is eligible for a substantial reduction in most of the FDA user fees, including De Novo. The CDRH is responsible for the Small Business Program that determines whether a business is qualified.
Medical Device User Fee Amendments (MDUFA) guidance documents can provide more detailed information about all FDA user fees.
4. The initial request process serves only to determine if the De Novo request is administratively acceptable based upon the Acceptance Checklist. The initial acceptance is followed by substantive review which will determine the final risk classification of your device.
5. A Pre-Submission (Pre-Sub) is a formal written request for feedback from the FDA that is provided in formal written form, and then followed by a meeting. Although a Pre-Sub is not required prior to a De Novo request, it can be extremely helpful to receive early feedback, especially for devices that have not previously been reviewed under a 510(k). If you think you would like to submit a pre-sub first, there are suggested guidelines for submission you should consider:
- Describe your rationale for a Class I or Class II classification for your device.
- Provide the search results of FDA public databases and other resources used to determine that no legally marketed device and no classification for the same device type exists.
- Provide a list of regulations and/or product codes that may be relevant.
- Provide a rationale for why the subject device does not fit within and/or is different from any identified classification regulations, based on available information.
- Identify each health risk associated with the device and the reason for each risk.
- Briefly describe any ongoing and/or planned protocols/studies that need to be completed in order to collect the necessary data to establish the device’s risk profile.
- Provide information regarding the safety and effectiveness of the device. Cite the types of valid scientific evidence you anticipate providing in your De Novo request, including types of data/studies relating to the device’s safety and effectiveness.
- Briefly describe any ongoing and/or planned protocols/studies that need to be completed to collect the necessary safety and effectiveness data.
- Provide protocols for non-clinical and clinical studies (if applicable), including how they will address the risks you anticipate and targeted performance levels that will demonstrate that general controls or general and special controls are sufficient to provide reasonable assurance of safety and effectiveness.
- Share any proposed mitigation measure(s)/control(s) for each risk, based on the best available information at the time of the submission. Highlight which mitigations are general controls and which are special controls and provide details on each.
- Include any other risks that may be applicable, in addition to those identified in the Pre-Sub, given the indications for use for the device.
- If applicable, provide any controls that should be considered to provide a reasonable assurance of safety and effectiveness for the device.
- Provide any non-clinical study protocols that are sufficient to allow the collection of data from which conclusions about device safety and/or effectiveness can be drawn. These protocols should address whether the identified level of concern is the appropriate level of concern for the device software, and if any additional biocompatibility and/or sterility testing is required.
- If clinical data is needed, provide information to show that the proposed study design and selected control groups are appropriate?
6. The FDA will attempt to review the De Novo request submission within 15 calendar days of receipt of the request to make a determination that the submission is declined or accepted for review. If they are unable to complete the review within the 15 days, your submission will automatically move to “accepted for review” status. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/de-novo-classification-process-evaluation-automatic-class-iii-designation
7. There are times when the FDA will refund your application fee. They have created a guidance document “User Fees and Refunds for De Novo Classification Requests” for the purpose of identifying:
- the types of De Novo requests subject to user fees
- exceptions to user fees
- the actions that may result in refunds of user fees that have been paid
When is a De Novo request subject to a user fee?
When will the FDA refund a De Novo user fee?
What fee must be paid for a new device submission following a De Novo “decline” determination?
To continue reading this eBook including a detailed walk-through of all the Traditional 510(k) components, submission requirements and timelines, and an overview of the other 510(k) forms including the Abbreviated 510(k) and the Special 510(k), please register to download the full version.
RIM - Master data management for RA teams
Large medtech companies often have data stored in multiple ERP, PLM, and eQMS systems due to mergers, acquisitions, and siloed growth within product teams and departments. While segmented data can cause issues for everyone, it provides particularly concerning obstacles for regulatory affairs teams. RA teams in large organizations typically manage multiple product lines with various levels of classification across many global markets. When product and registration data is not centralized, regulatory teams will not only encounter significantly more complex processes related to managing and controlling data properly, but will also struggle to find and organize the data needed for submissions, license renewals, and other standard RA activities.
Regulatory data management issues without RIM
- Maintaining validation records for multiple systems: In the highly regulated world of medical technology, manufacturers are required to fully validate any system used to design, develop, or manufacture a medical device. Among other things, manufacturers must be able to demonstrate that only the current, approved version of a device can be manufactured. System updates and other changes trigger a re-validation process, which becomes increasingly complex as the number of systems increases. Not only does the system that is being changed need to be validated again, but any other system and process that is using data from the updated/changed system may need to be validated again as well. Issues with data integration between systems is a common finding during quality and regulatory audits.
- Ensuring data accuracy: As mentioned above, validating systems becomes exponentially more complex as the number of systems increases. In cases where the same data is stored in more than one system, the possibility exists that the data is not synchronized in real-time. Whether data is automatically transferred between systems or requires manual data entry or integration steps, each integration point is a possible point of failure. Regulatory and quality teams need to ensure that they identify the “source of truth” for each piece of data that is duplicated and that they can demonstrate the processes that ensure data integrity is being maintained.
- Managing user access: Managing user permissions in large systems, such as ERP solutions, often involves setting specific permission levels for a large number of detailed system functions. Users with access to information in one system may not have access to the same information in another system, causing auditing issues and creating difficulty in administering user credentials. For example, does a user have access to add regulatory documentation, such as EU MDR technical files or medical device certificates, into the system? If not, many companies end up circumventing their own systems by also using SharePoint or other shared drives to store updated files – where they may get lost or overlooked.
- Establishing system-related processes: Establishing and maintaining processes for system issues, downtime, updates, and other regular maintenance is impacted by the number of systems and the ways in which they are integrated. Regulatory teams won’t control these processes for non-regulatory systems, but may require access to data in these systems for time-critical tasks.
Regulatory workflow issues without RIM
Regulatory affairs professionals are familiar with the massive, color-coded spreadsheets that are often central to maintaining medical device registration information. While those spreadsheets work in some situations, without a centralized RIM system RA teams face two large challenges:
Software solutions not built for regulatory teams
- Spreadsheets are not the answer: While those large spreadsheets can be sufficient in smaller companies with a few products in a few markets, they quickly become unwieldy. Regulatory teams managing multiple submissions projects across global markets are compiling large amounts of information into specifically formatted portfolios for each country – a process that is difficult, at best, to manage with spreadsheets and pdf documents.
- Non-compliance risks: Regulatory teams that are managing data without a centralized RIM solution also run the risk of identifying changes and expiration dates too late, leading to higher consultant costs and the risk of non-compliant products.
- Missed opportunities: Most regulatory teams do an amazing job keeping multiple projects on track, products in compliance across the globe, and their company prepared for audits and inspections. What if, however, regulatory teams had access to a centralized regulatory system that could provide them with the information, and the time, to contribute to strategic product marketing and staffing decisions? We believe that an organization with a revenue-aligned, strategic regulatory team has a competitive advantage in the marketplace. Read more in our ebook, Regulatory Strategy as a Competitive Advantage.
Regulatory data in multiple systems
We know that 70% of regulatory teams spend at least half of their time on repetitive administrative tasks. Much of this is because the data they need is stored in multiple systems across the organization, with the same data often being stored in multiple places. This leads to an increased chance of outdated information being used, required data being missed, and difficulties in proving that the data management processes in place are sufficient for ensuring accuracy.
The information required by regulatory teams comes from teams throughout an organization, including product data from the engineering team, production and supplier information from the manufacturing team, quality records from the QA team, clinical trial data from the clinical team, and more. This is all in addition to the regulatory submissions, changes, and agency communications managed by the RA team themselves. Without a centralized system to record and reference all of this data, regulatory teams are left to a lot of research, searching, and duplication of efforts across the team.
Data warehouses as an option
In cases where there are multiple, enterprise-level systems sharing the same data, a data warehouse is often used. Data warehouses provide a centralized system in which to store data and maintain that single “source of truth” that all systems can pull data from. However, these systems can be extremely expensive and complex to set up and maintain. They normally require a team of consultants or internal staff to manage the setup and maintenance of the warehouse, including complex ETL (extract, transform, and load) workflows. These workflows are required because data stored in multiple systems will almost never be in the same format and will need to be “transformed” before being loaded into the data warehoused.
In addition, data warehouses are not typically updated in real-time and require that data cleaning and verification procedures run before data is uploaded. This makes a data warehouse a poor option for data that is needed for daily workflows and processes, such as UDI data management.
Regulatory Information Management (RIM) systems as a better option for master regulatory data management
Regulatory Information Management (RIM) systems, such as Rimsys, are designed to be the central source of truth for regulatory information. Purpose-built for regulatory teams, RIM solutions are powerful because they provide:
Centralized, product-centric, regulatory data
Information and data that is specific to regulatory activities can be stored and accessed directly in the RIM solution. This includes information such as submission documents, registration certificates, product references to standards and essential principles, and regulatory authority communications. The RIM solution is the original “source of truth” for this information.
As a result, RIM solutions provide regulatory teams with control over critical data, such as “available to sell” flags at a product version and country or market level. This ensures that the regulatory team is managing a product’s availability to be sold, market-by-market, based on its regulatory status in each market.
Integrated data
Regulatory teams require data from across the organization to manage submissions and other regulatory activities. A strong RIM solution will provide for integration with PLM, eQMS, eDMS, ERP, and other solutions that typically house information used by regulatory teams. For example, the design and engineering teams will likely utilize a PLM system to manage product details and revisions. While that data is needed by the regulatory team, it is owned by the design and engineering teams and belongs in their PLM system.
Rimsys provides secure API endpoints that simplify integration with nearly any system with a REST API.
Rimsys also simplifies compliance with 21CFR part 11 and other regulations by providing complete and easy-to-read activity logs for all actions taken within the software.
To learn more about how Rimsys can be your master data management system, schedule a time with one of our product experts to see Rimsys in action.
EU country-specific medical device registration requirements
There are 27 member states that belong to the European Union (EU), along with additional countries that participate in the European Economic Area (EEA) and the EU’s single market. One of the benefits of belonging to the EU is the unification of regulations for medical devices and in-vitro diagnostics. As you know, registering medtech devices (ultimately known as applying the CE Mark) is a complex process. Applying the CE Mark allows your devices to easily be imported and sold throughout Europe.
Some of the member states and those participating in the single market require additional registration steps beyond those required by the EU for class IIa, class IIb, and class III medical devices. In general, a medical device manufacturer is required to submit a registration form and/or enter information in the online database before placing the product on the market. Typically, this notification includes the upload of a localized label, instructions for use, Declaration of Conformity, and the CE certificate.
The additional registration requirements apply to manufacturers outside of the EU who wish to market devices in an EU member country. Most markets will also have additional or different registration requirements for local Authorized Representatives and Manufacturers. Once EUDAMED is fully implemented, the assumption is that most of these country-specific registration requirements will be removed.
The table below lists all 27 EU member states, along with additional countries that participate in the EU single market. This table is for reference only – Regulatory professionals are urged to consult country Competent Authority websites for country-specific requirements.
* Countries not in the EU
+ Devices supported by Finnish distributors to hospitals and retailers require notification.
++ Registration may be required if an importer, authorized representative, or manufacturer located in Germany is placing the product on the market for the first time.
Note: Specific requirements for local economic operators are not included here and may include both additional entity and device registration requirements.
FDA transition plans for Covid-19-related medical devices
New guidance
The FDA has issued two final guidance documents intended to assist with transition plans for medical devices that are currently being distributed under emergency use authorizations (EUAs) or that fall under specific policies issued to support the response to the COVID-19 pandemic. The agency states that they recognize that it will take time for manufacturers and others to adjust to “normal operations” as policies adopted during the pandemic come to an end. However, they are recommending that organizations move quickly to plan their regulatory strategy and engage with the agency where necessary.
The two guidance documents are:
- Transition Plan for Medical Devices Issued Emergency Use Authorizations (EUAs) Related to Coronavirus Disease 2019 (COVID-19) Guidance
- Transition Plan for Medical Devices that Fall Within Enforcement Policies Issued During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency
Transition periods
Advance notices will be published in the Federal Register for each EUA declaration 180 days prior to the termination of the EUA.
For devices that fall within enforcement policies issued during the COVID-19 public health emergency (PHE), a 180-day transition period is also available and will begin following the expiration of the section 319 PHE declaration. Manufacturers should refer to the following “list 1” COVID-19 public health emergency enforcement policies for more detail:
- Digital pathology devices
- Imaging systems
- Non-invasive fetal and maternal monitoring devices
- Telethermographic systems
- Treating psychiatric disorders
- Extracorporeal membrane oxygenation and cardiopulmonary bypass devices
The FDA’s stated intent with this guidance is to, among other things, “help avoid disruption in device supply and help facilitate compliance with applicable FD&C act requirements after the termination of the relevant EUA declaration…”
Guiding principles
The following guiding principles are taken directly from the guidance documents listed at the beginning of this article, and they are the same in both documents.
- This guidance is intended to help facilitate continued patient, consumer, and healthcare provider access to devices needed in the prevention, treatment, and diagnosis of COVID19.
- FDA believes the policies and recommendations in this guidance will help to ensure an orderly and transparent transition for devices that fall within the scope of this guidance. FDA’s policies and recommendations in this guidance are consistent with the Agency’s statutory mission to both protect and promote the public health.
- FDA’s policies and recommendations follow, among other things, a risk-based approach with consideration of differences in the intended use and regulatory history of devices, including whether the device is life-supporting or life-sustaining, capital or reusable equipment, a single-use device, and whether another version of the device is FDA cleared or -approved.
- As always, FDA will make case-by-case decisions regarding the enforcement of legal requirements in response to particular circumstances and questions that arise regarding a specific device or device type. This may include FDA revising or revoking an EUA,29 requesting a firm initiate a recall (see 21 CFR 7.45), or taking other actions, including an enforcement action. Moreover, FDA may revise the enforcement policies and recommendations in the guidance, as appropriate.
Do not wait to submit marketing submissions
Manufacturers who intend to seek market authorization for devices currently under COVID-19-related EUAs should begin working on their market submission and transition implementation plan as soon as possible. The CDRH is encouraging organizations that want to continue marketing their device, and need a marketing submission, to take advantage of the full transition period, including submitting a pre-submission if needed. The pre-submission process allows for early interactions with the CDRH.
Nonconformance reporting for medical device manufacturers
Defining nonconformance
Very simply, a nonconformance occurs when a specification is not met. The FDA defines a specification in 21 CFR 820.3 as “any requirement with which a product, process, service, or other activity must conform,” and ISO 13485:2016 as a “need or expectation that is stated, generally implied, or obligatory.”
While managing nonconformance starts with fully defining specifications; it is the identification, tracking, and resolution of nonconformance that is a focus of medtech quality and regulatory teams and a requirement of both ISO 13485:2016 and the FDA’s 21 CFR Part 820 quality system regulation.
Identifying nonconformance occurrences
As part of a compliant quality system, medical device manufacturers should implement procedures to identify and address both major and minor non-conformances. Nonconformances may be identified through processes found in multiple subsystems that are part of an overall quality management system within the organization.
The systems and subsystems in which nonconformances are identified typically include:
- ERP
- Regulatory information management (RIM)
- Product lifecycle management (PLM)
- Document management
- Customer service / customer management
- Complaint handling
- Device history records
- Audit management
- CAPA
- Training/learning management
- Calibration/preventative maintenance
- Development change management
Evaluating nonconformance
Once a nonconformance is identified, it should be evaluated in a timely manner, and a determination made as to the disposition of any affected products. Requirements for additional investigation and reporting should also be identified. Based on the severity of the nonconformance and its effect on the safety and efficacy of devices being manufactured or already in the market, a CAPA (corrective/preventative action) record may need to be created. In the U.S., this is defined in the quality regulation 21 CFR Part 820.100.
To disposition a nonconformance, consider the following:
- Will the existing system detect the nonconformance if it recurs in time for remediation?
- How likely is it that this issue will recur?
- What is the impact of the non-conformance (i.e., could it affect patient health)?
Issues that are more severe or are more likely to recur should trigger a more immediate and comprehensive response.
Nonconformances that are escalated and handled under CAPA are based on risk and can include those that have or could have an impact on a product or process that is:
- Not easily corrected
- Recurring
- Severe
In addition, nonconformances that rise to the level of a CAPA require significant resources and typically result in a full project to identify root cause(s), containment, and corrective actions, and monitoring for effectiveness.
Nonconformances that don’t require a CAPA have simpler resolutions that include documenting actions taken to correct the issue (or justification for no action). If the issue is not recurring, there may be no other action required. For example, a nonconforming material received from a vendor may be a singular issue that was easily identified through existing inspection procedures and is not expected to recur. In this case, the material is returned to the vendor and no additional action is required.
Processes that are out of conformance are often resolved through improved documentation and/or additional user training. However, be sure that the true root cause of the nonconformance is identified as procedural nonconformances can signal additional issues.
Documenting nonconformances
An important part of nonconformance procedures is the nonconformance report (NCR) or other documentation procedures. Nonconformances are typically documented within the subsystem in which they were identified. Some organizations will have a nonconforming system in which issues originating from all subsystems are documented. Centralized nonconformance systems allow for trending and other analysis across all subsystems, the results of which may generate CAPAs.
The requirements for documenting a nonconformance may vary by subsystem. In general, however, nonconformance documentation records:
- The requirement/specification that was not met.
- The objective evidence supporting the determination.
- The action that is being taken to address the nonconformity.
Nonconformances are a common point of focus during quality audits by regulatory bodies, including the FDA, and should follow a well-documented process. Auditors will often try to determine if the quality system is functioning effectively by looking at self-identified nonconformances and comparing them to externally reported nonconformances. This is to ensure that nonconforming products were not released, or that the appropriate actions were taken to resolve issues in the field.
The importance of nonconformance reports
Nonconformances related to distributed products of higher risk result in nonconformance reports issued to government authorities through vigilance reporting, medical device reporting, and field action/recall reports. For example, the FDA requires that a medical device report be submitted within 30 days of a serious adverse event (see 21 CFR Part 803 Subpart E). Strong reporting procedures for nonconformances of all types are important in identifying trends, addressing issues before they become critical, and as part of a complete quality management system.
A nonconformance reporting procedure is only part of a strong quality system. Read An overview of 21 CFR part 820 and ISO 13485 overview for more information on establishing quality systems for medtech companies.
Regulatory strategy as a competitive advantage
This article is an excerpt from the Regulatory strategy as a competitive advantage ebook.
Table of Contents
- The regulatory revenue opportunity
- Regulatory responsibilities
- Limitations of the "cost-center" approach to regulatory affairs
- Regulatory as a revenue function
- Competitive advantage #1: Faster time to market
- Competitive advantage #2: Cost avoidance
- Competitive advantage #3: Out-pacing competitors
- Why invest in regulatory/revenue alignment?
- Getting started - 3 steps to move towards a revenue-aligned RA team
It is well known that medical technology (medtech) companies are highly regulated, given the potential risks their products present. Understanding and complying with the complex regulations in each country is, therefore, a necessary part of marketing and selling medical devices. To realize any revenue from a medical device, it must not only demonstrate compliance with all applicable regulations, it must also receive and maintain market clearance from each country in which it is to be sold. No market clearance means no revenue. Given the key role regulatory compliance plays in revenue attainment, regulatory teams, tools, and processes present a significant opportunity for differentiation for organizations willing to invest in them.
For the majority of medtech companies, however, regulatory departments have traditionally been treated as operational cost centers, with departmental improvements focused on cost reduction and efficiency improvements. Limited investment in people and tools, and limited interest in digital transformation, have left regulatory teams across the medtech industry underfunded and under-resourced.
This has led to great resourcefulness within the RA community, where most members can point to heroes within their team who worked long hours to meet a submission deadline, headed off a disaster by uncovering a pending expiration, created ad-hoc systems to organize information and streamline communication between the RA and QA teams for smoother audits, or have otherwise gone above and beyond their typical responsibilities.
Regulatory teams, however, have the potential to be a revenue-driving competitive weapon for companies that are willing to look at them a little differently and invest in regulatory performance above regulatory cost-effectiveness. Well-supported regulatory teams can provide a true competitive advantage by providing the resources and direction to:
- Capture market share by being first to market with novel devices.
- Avoid lost revenue by effectively tracking and planning for registration renewals/updates.
- Out-pace competitors and grow market share by adapting to regulatory changes more quickly and taking advantage of competitors’ non-compliance or inability to enter a new market.
We believe we are entering a new era for regulatory affairs within the medtech industry. One in which RA teams have a seat at the table when go-to-market, competitive positioning, and strategic decisions are being made.
In the medtech industry, regulatory affairs (RA) teams have a broad range of responsibilities across the product lifecycle:
Premarket regulatory strategy
Obtaining market clearance for a new medical device is the primary activity typically attributed to RA teams. It is not unusual for a regulatory team to be given market entrance projects with little warning, but ideally, the RA team would be brought in as early as possible to contribute to go-to-market discussions.
Premarket regulatory strategy, at a minimum, involves:
- Determining the most appropriate pathway to market approval. For example, a 510(k) or PMA submission in the U.S.
- Working with quality, product, and other teams to gather information needed for market submission.
- Establishing communication with applicable regulatory bodies and third-party approved auditors.
- Compiling and submitting required documentation for market approval. This includes managing follow-up activities, questions, and requests for additional information throughout the approval process.
Forward-thinking organizations often look to bring in RA teams even earlier in the process. As regulatory experts, RA professionals can provide unique insight into product development plans. In consultation with R&D teams, can help to refine product strategies, and steer development in areas that will reduce regulatory hurdles when new products are ready to be commercialized.
Maintaining regulatory compliance for existing products
While the primary focus of regulatory teams is often considered to be new market submissions, the majority of their time is actually spent on maintaining compliance for products that are already in-market. Even in situations where market registrations do not expire, constant vigilance is required to ensure that devices remain compliant with current regulations. These efforts take a considerable time for a typical RA team because information is often spread across disparate systems, where it can be difficult to find and confirm.
Maintaining regulatory compliance for approved devices includes:
- Staying on top of changing standards and making changes as required to existing technical files and other documentation.
- Submitting appropriate documentation updates when there is a change made that could potentially affect the efficacy or safety of the product, such as a material switch or facility change.
- Understanding pending regulatory changes and proactively addressing any that have an impact on devices currently in-market.
- Tracking registration expirations and preparing for timely re-submissions to ensure there is no lapse in market clearance.
Post-market activity
Post-market surveillance and vigilance activities are required by most countries and should involve the cooperation of the quality and regulatory teams. Ensuring that changing post-market reporting requirements are understood and complied with is an important regulatory responsibility.
Regulatory teams typically play a role in:
- Post-market surveillance of adverse events, complaints, and any issues associated with a device in the field.
- Assembling and submitting any required periodic safety reports to country/regional health authorities.
- Post-market vigilance and reporting of serious events to the appropriate regulatory agencies.
- Any required communication with regulatory authorities regarding adverse events or concerning trends in product quality.
Ask any RA professional, and they are likely to tell you that they work long hours and are often scrambling to meet looming deadlines...
To continue reading this ebook, download the full version.
Essential principles
What are Essential Principles?
Essential Principles (EPs) are requirements established by a country’s health agency. Medical device manufacturers need to prove that they comply with these requirements in order to sell their device in each country where they are required. This is often tracked in a burdensome table in which each requirement is explained by applicable standards and other items used to demonstrate compliance with each requirement. The manufacturer will link their evidence files to prove that they meet the requirement or provide an explanation as to why it is not applicable in their situation.
Think of this like cliff-notes for the submission and related documents. Submission documents, their locations, and explanations can all vary depending on the device type, manufacturer, and their processes.
What countries require Essential Principles?
Not every country requires EPs for their submissions. Some of the main countries that do require them include:
- The European Union – where they are called General Safety and Performance Requirements (GSPR)
- Australia
- Malaysia
- Singapore (accepts EU documentation in most cases)
- China
What do Essential Principles look like?
GSPR (General Safety and Performance Requirements) in the European Union are an example of Essential Principles requirements. The language in the GSPR comes directly from Annex 1 of the EU MDR of 745/2017 for medical devices and EU IVDR 2017/746 for in-vitro diagnostic devices. Medical device manufacturers are taking the text of this regulation, numbering and all, and documenting whether they apply to it, the standards that they apply to, and then providing their evidence.
Let’s look at an example that directly comes from EU MDR 2017/745, Regulatory text, Annex I, 7th requirement:
“Devices shall be designed, manufactured and packaged in such a way that their characteristics and performance during their intended use are not adversely affected during transport and storage, for example, through fluctuations of temperature and humidity, taking account of the instructions and information provided by the manufacturer.”
The validation of the Essential Principles for this particular requirement would be displayed in a table like the one below. Note that the description column in the table and in the EU MDR regulatory requirement are identical to each other.
These tables change constantly, and it is a large administrative burden on the regulatory professional to quickly identify changes, perform a gap analysis (check for changes and do testing if needed), and update the tables when required. In addition, we have seen the following issues caused by changing standards:
- Large companies can have hundreds to thousands of Essential Principles tables. Without a bulk upload, this can take an incredibly long time to process all of those documents.
- Errors can occur with standards updates by missing a product that is associated to a standard.
- If a gap analysis is done too late and testing a product to a revised or new standard is required - your product might need to be blocked from a market for months, which could mean massive revenue loss.
- Accidentally missing a reference to new testing data because only the standard was updated.
Rimsys allows regulatory professionals to be notified of standard changes and even do bulk additions and deletions of documents, standards and certificates to your Essential Principles Tables, which can save regulatory professionals countless hours in administrative work. For more information on how one of our customers benefited from our Essential Principles tool, reducing their EP and GSPR maintenance by 99%, read our Bisco case study.
