The U.S. market is one of the most attractive markets in the medical technology industry due to its population of over 320 million. However, the American approval system differs significantly from the European system: There are product classification codes and individual risk classifications of medical products. The U.S. regulatory authority FDA (Food and Drug Administration) has decision-making sovereignty here. Depending on the American product classification, a specific and generally complex approval procedure is required.

U.S. Agent
The FDA requires all medical device manufacturers located outside the USA to nominate a U.S. agent located in the USA. This agent serves as a contact point for the FDA if the company abroad is not available to the FDA. This includes planning inspections at the manufacturer and production sites or forwarding and answering questions from the FDA to the manufacturer (foreign manufacturer) regarding the products to be imported.

Registration of Companies and Listing of Products
All companies involved in the production or distribution of medical devices in-tended for the U.S. market must register their facilities for a fee. In addition, all products to be marketed in the USA must be listed in the FDA database before being introduced into the U.S. market. The listing must be constantly updated, and the fee paid annually. Further information (such as fees) can be found under Medical Device User Fee Amendments (MDUFA) on the FDA website.

FDA 513(g) Classification of Medical Devices
There are situations in which it is difficult to clearly assign medical devices to a U.S. classification. The American system is based on product codes and product categories of already known medical devices. If a manufacturer wants to develop new and innovative medical devices, combine known technologies or further develop existing methods and make them available on the market, there may be a need for clarification regarding the applicability of existing codes, the resulting classification and the identification of the necessary approval path. The planned classification and approval strategy should therefore be discussed with the FDA to avoid the rejection of an approval and the resulting expenditure for further activities.

Pre-submission meetings with the FDA can help mitigate this risk. Another option is the FDA’s 513(g) program, where the manufacturer submits a short documentation consisting of a description of the medical device, its intended use and intended purpose, and the intended labeling and promotional materials.
As a result of the submission under the 513(g) program, the manufacturer then receives feedback on the classification (class of device) within the generic product group (classification regulation), as well as information on the necessary approval route and, if available, information on additional requirements such as applicable FDA guidance or special requirements such as requirements for radiation protection, if applicable.

FDA Premarket Notification 510(k)
Manufacturers of Class II (and some Class I and Class III) medical devices normally require an FDA clearance for their product before it can be placed on the U.S. market.

This requires filing documents under Section 510(k) of the Federal Food, Drug and Cosmetic Act. The FDA must determine whether the medical device is substantially equivalent to a medical device already on the market. In addition, the requirements of applicable recognized consensus standards and FDA guidelines are examined. Manufacturers must prove the equivalence of the intended purpose and the technological properties. Comparative tests can be used for this purpose. As far as the technological aspects are concerned, proof can be provided that safety and performance is not impaired, provided the deviations are not significant. This can be done by fulfilling standards and guidance or by clinical data. If proof of equivalence cannot be provided, the medical device manufacturer may have to undergo a cost-intensive and time-consuming pre-market approval (PMA) process or the alternative de novo process for assigning a classification by the FDA.

The premarket notification is needed not only when placing new Class II devices on the market, but also when modifying a product that already has a 510(k) release. Further developments of the own product portfolio should therefore be carried out in close coordination and cooperation with regulatory affairs experts. Here you benefit from our extensive experience in the creation of pre-market notification 510(k)s.

FDA Premarket Approval for Class III Medical Devices
A premarket approval application (PMA) is the strictest, most complex and most cost-intensive type of approval issued by U.S. authorities. The application re-quires approval by the FDA, which is achieved through a comprehensive and detailed submission dossier, ideally prepared during the development phase and agreed with the FDA. The documentation is reviewed in detail and after 180 days a meeting is arranged with the applicant. In this meeting, open questions, deficiencies and FDA expectations are discussed. The authority bases its decision on scientific results to ensure that the medical product can safely and effectively fulfil its intended purpose. Clinical data is an essential part of the ad-ministration documentation and is usually generated as the result of a clinical trial.

FDA Investigational Device Exemption (IDE)
An IDE is required to conduct a clinical trial in the USA. Before a product can be used in a clinical trial on patients, its safety and efficacy must be demonstrated. Some FDA requirements for marketing products commercially, such as some labeling requirements, are dropped.

Depending on the product’s risk rating, different parties are involved in evaluating the IDE application:
For non-significant-risk devices, an institutional review board (IRB), similar to an ethics committee, reviews the IDE documentation and accepts the study.

For significant-risk devices, the applicant submits documentation to the FDA and IRB. They review the documentation and accept the study.

A clinical trial in the USA may only be initiated after the application has been successfully examined and used, for example, to generate clinical data as part of a PMA. We have extensive expertise in this area, including staff members who are former FDA employees, who can help you with the complex issues of PMA and IDE.

For more information and to see our experts in the U.S., please see NSF’s Medical Devices Regulatory Support and Submission web page.

FDA Inspections
As part of its monitoring activities, the FDA carries out regular inspections of manufacturers and manufacturer production sites. These inspections differ fundamentally from the audits of notified bodies in Europe. The aim of these inspections is to determine non-conformities of a company regarding the relevant U.S. requirements (e.g. Quality System Regulation 21 CFR Part 820). Manufacturers of high-risk products are also inspected as part of the PMA process, and the associated production processes and quality management system are thoroughly reviewed.

The FDA carries out three types of inspections:
(1) Pre-approval inspections of submissions for certain approvals and products or under special circumstances
(2) Routine inspections
(3) For-cause inspections of specific problems

How We Can Help
We offer various services for the successful approval of your medical device in the USA. We can support you in:

  • Search and recommendations of a U.S. agent
  • Registration of your company and products in the FDA database
  • Classification of medical devices
    • Analysis of the possible product class
    • Analysis and identification of applicable U.S. regulations (guidances, recognized consensus standards and, if applicable, performance standards)
    • Application 513(g)
  • Premarket notification 510(k) and premarket approval (PMA)
    • Identification or evaluation of possible comparison products (predicate devices)
    • Preparation and dispatch of documentation
    • Takeover of communication with the FDA
    • Assistance in answering queries
  • Investigational device exemption (IDE)
    • Creation and dispatch of documents
    • Accompaniment or assumption of the communication
  • Preparation and support during inspections by the FDA
    • Detailed analyses of QSR compliance
    • Implementation of processes according to QSR (21 CFR Part 820)
    • Evaluation of existing validations and implementation of valida-tion projects (Q-SW as well as production and test SW)
    • Training of employees before upcoming FDA inspections (be-havior, inspector’s approach to inspections (QSIT))
    • Strategic planning as preparation for a successful inspection for the manufacturer or contract manufacturer
    • Mock inspections to check compliance, including MDSAP
    • Assumption of responsibility in the back office (coordination and release of documentation to the FDA inspector)
    • Taking over the communication with FDA inspectors in the front office as translator or direct responsible person (e.g. in case the QM representative is not fluent in English)

    For further details on regulatory affairs or for a non-binding offer, please contact us or find out about our latest seminar.