Medical Device Strategy - Architecture
Medical device development strategies, plan & implementation architecture. Creative solutions for 510(K), PMA, IDE, De Novo, Predicate based programs. Device Safety Programs.
Synergy Research designs medical device programs for regulatory submissions on a regular basis, with a significant number of filings on an annual basis. We are familiar with FDA expectations on 510(k) filings, pre-IDE programs, IDE submissions, PMA programs. FDA does not provide detailed instruction on 510(k) filings, as such, companies need to have traveled this path in the past, and know what needs to be accomplished, as well as what to stay away from.
We analyze each medical device within the framework of what is currently known about the device; from outside sources, client, subcontractors, medical & scientific, safety & efficacy, engineering & manufacturing, testing & compliance. We review what the required path is and information required for such, based on the minimum expected within the 510(k) process.
FDA does not offer a template for 510(k) submissions that must be followed, but it must address the key 21 areas as follows:
1. Medical Device User Fee Cover Sheet (Form FDA 3601)
2. CDRH Premarket Review Submission Cover Sheet
3. 510(k) Cover Letter
4. Indications for Use Statement
5. 510(k) Summary or 510(k) Statement
6. Truthful and Accuracy Statement
7. Class III Summary and Certification
8. Financial Certification or Disclosure Statement
9. Declarations of Conformity and Summary Reports
10. Executive Summary
11. Device Description
12. Substantial Equivalence Discussion
13. Proposed Labeling
14. Sterilization and Shelf Life
17. Electromagnetic Compatibility and Electrical Safety
18. Performance Testing – Bench
19. Performance Testing – Animal
20. Performance Testing – Clinical
Synergy Research 510(k) filings past 13 years:
Synergy Research performs many device filings on a regular basis. We act as US Agents for multiple international device manufacturers; 510(k), IDE, PMA
What you need to know; What we know on behalf of your program:
Establishment Registration - 21 CFR Part 807
Manufacturers (both domestic and foreign) and initial distributors (importers) of medical devices must register their establishments with the FDA. All establishment registrations must be submitted electronically unless a waiver has been granted by FDA. All registration information must be verified annually between October 1st and December 31st of each year. In addition to registration, foreign manufacturers must also designate a U.S. Agent. Beginning October 1, 2007, most establishments are required to pay an establishment registration fee.
The schedule of registration fees for fiscal years as follows:
Any foreign establishment engaged in the manufacture, preparation, propagation, compounding, or processing of a device imported into the United States must identify a United States agent (U.S. agent) for that establishment.
Information about a foreign establishment’s U.S. agent is submitted electronically using the FURLS system and is part of the establishment registration process. Each foreign establishment may designate only one U.S. agent. The foreign establishment may also, but is not required to, designate its U.S. agent as its official correspondent. The foreign establishment should provide the name, address, telephone and fax numbers, and e-mail address of the U.S. agent.
Responsibilities of a U.S. Agent
The U.S. agent must either reside in the U.S. or maintain a place of business in the U.S. The U.S. agent cannot use a post office box as an address. The U.S. agent cannot use just an answering service. They must be available to answer the phone or have an employee available to answer the phone during normal business hours.
The responsibilities of the U.S. agent are limited and include:
assisting FDA in communications with the foreign establishment,
responding to questions concerning the foreign establishment's devices that are imported or offered for import into the United States,
assisting FDA in scheduling inspections of the foreign establishment and
if FDA is unable to contact the foreign establishment directly or expeditiously, FDA may provide information or documents to the U.S. agent, and such an action shall be considered to be equivalent to providing the same information or documents to the foreign establishment.
Please note that the U.S. agent has no responsibility related to reporting of adverse events under the Medical Device Reporting regulation (21 CFR Part 803), or submitting 510(k) Premarket Notifications (21 CFR Part 807, Subpart E)
Medical Device Listing - 21CFR Part 807
Manufacturers must list their devices with the FDA. Establishments required to list their devices include:
Contract manufacturers that commercially distribute the device,
Contract sterilizers that commercially distribute the device,
Re-packagers and re-labeler's,
Re-processors single-use devices,
Manufacturers of accessories and components sold directly to the end user
U.S. manufacturers of "export only" devices
Premarket Notification 510(k) - 21 CFR Part 807 Subpart E
If your device requires the submission of a Premarket Notification 510(k), you cannot commercially distribute the device until you receive a letter of substantial equivalence from FDA authorizing you to do so. A 510(k) must demonstrate that the device is substantially equivalent to one legally in commercial distribution in the United States: (1) before May 28, 1976; or (2) to a device that has been determined by FDA to be substantially equivalent.
On October 26, 2002 the Medical Device User Fee and Modernization Act of 2002 became law. It authorizes FDA to charge a fee for medical device Premarket Notifcation 510(k) reviews. A small business may pay a reduced fee. The application fee applies to Traditional, Abbreviated, and Special 510(k)s. The payment of a premarket review fee is not related in any way to FDA's final decision on a submission.
The review fees for 510(k) submissions are below:
The applicable fee corresponds with the date of receipt of the submission by FDA. Please note that FDA will consider the 510(k) submission incomplete and will not accept it for filing until the fee is paid in full. That is, the date of receipt is the date that the submission has been received AND the fee is paid in full.
The following exemptions or waivers apply:
Premarket Approval (PMA) - 21 CFR Part 814
Product requiring PMAs are Class III devices are high risk devices that pose a significant risk of illness or injury, or devices found not substantially equivalent to Class I and II predicate through the 510(k) process. The PMA process is more involved and includes the submission of clinical data to support claims made for the device.
Beginning fiscal year 2003 (October 1, 2002 through September 30, 2003), medical device user fees apply to original PMAs and certain types of PMA supplements. Small businesses are eligible for reduced or waived fees.
For fiscal year 2010 (October 1, 2009 through September 30, 2010), the fees for PMA applications are:
* PMA=Premarket Approval; PDP=Product Development Protocol; BLA=Biologics License Application; PMR=Premarket Report (for a reprocessed device)
Investigational Device Exemption (IDE) - 21CFR Part 812
An investigational device exemption (IDE) allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support a Premarket Approval (PMA) application or a Premarket Notification 510(k) submission to FDA. Clinical studies with devices of significant risk must be approved by FDA and by an Institutional Review Board (IRB) before the study can begin. Studies with devices of nonsignificant risk must be approved by the IRB only before the study can begin.
Quality System Regulation (QS)/Good Manufacturing Practices (GMP) - 21 CFR Part 820
The quality system regulation includes requirements related to the methods used in and the facilities and controls used for: designing, purchasing, manufacturing, packaging, labeling, storing, installing and servicing of medical devices. Manufacturing facilities undergo FDA inspections to assure compliance with the QS requirements.
. . .
Labeling - 21 CFR Part 801
Labeling includes labels on the device as well as descriptive and informational literature that accompanies the device.
The U.S. Food and Drug Administration (FDA) develops and administers regulations under authority granted by laws passed by Congress that apply to food, drugs, cosmetics, biologics, radiation-emitting electronic products, and medical devices. Labeling regulations pertaining to medical devices are found in the following Parts of Title 21 of the Code of Federal Regulations (CFR).
General Device Labeling -
In Vitro Diagnostic Products -
Investigational Device Exemptions -
Good Manufacturing Practices -
General Electric Products -
Medical Device Reporting - 21 CFR Part 803
Incidents in which a device may have caused or contributed to a death or serious injury must to be reported to FDA under the Medical Device Reporting program. In addition, certain malfunctions must also be reported. The MDR regulation is a mechanism for FDA and manufacturers to identify and monitor significant adverse events involving medical devices. The goals of the regulation are to detect and correct problems in a timely manner.
On July 31, 1996, the new Medical Device Reporting (MDR) regulation became effective for user facilities and device manufacturers. This document describes the current provisions for device manufacturers.
The MDR regulation provides a mechanism for FDA and manufacturers to identify and monitor significant adverse events involving medical devices. The goals of the regulation are to detect and correct problems in a timely manner. Although the requirements of the regulation can be enforced through legal sanctions authorized by the Federal Food Drug & Cosmetic (FFD&C) Act, FDA relies on the goodwill and cooperation of all affected groups to accomplish the objectives of the regulation.
The statutory authority for the MDR regulation is section 519(a) of the FFD&C Act as amended by the Safe Medical Devices Act (SMDA) of 1990. The SMDA requires user facilities to report:
device-related deaths to the FDA and the device manufacturer;
device-related serious injuries to the manufacturer, or to FDA if the manufacturer is not known; and
submit to FDA on an annual basis a summary of all reports submitted during that period.
The SMDA requires FDA to issue regulations requiring distributors to report device-related deaths, serious injuries and reportable malfunctions. On September 1, 1993, FDA published a final MDR reporting regulation for distributors, including provisions for importers that became effective on October 1, 1993. In addition, the SMDA requires distributors and manufacturers to certify to FDA the number of MDR reports filed or that no reports have been filed.
Who must submit a 510(k) Premarket Notification?
Manufacturers / importers of some Class 1 and Class 3, and most Class 2 medical devices are required to file 510(k)s.
Details on where 510(k)s are required, or not required, please proceed to the following page.
Medical Device Exemptions 510(k) and GMP Requirements
Following is a breakdown of 510(k) exempt and Good Manufacturing Practice (GMP)/Quality System exemptions listed by device class. All devices in this list are 510(k) exempt unless further qualified by a footnote. Only devices annotated by (*) are also exempt from GMP except for general recordkeeping requirements and compliant files.
Class I Devices
FDA has exempted almost all class I devices (with the exception of Reserved Devices from the premarket notification requirement, including those devices that were exempted by final regulation published in the Federal Registers of December 7, 1994, and January 16, 1996. Some 510(k) exemptions annotated with "\#\" are with certain limitations as noted in the footnotes. It is important to confirm the exempt status and any limitations that apply with 21 CFR Parts 862-892. Limitations of device exemptions are covered under 21 CFR xxx.9, where xxx refers to Parts 862-892.
If a manufacturer's device falls into a generic category of exempted class I devices as defined in 21 CFR Parts 862-892, a premarket notification application and FDA clearance is not required before marketing the device in the U.S. However, these manufacturers are required to register their establishment by submitting Form FDA 2891, "Initial Registration of Device Establishment," and list the generic category or classification name of the device by submitting Form FDA 2892, "Device Listing."
IMPORTANT NOTE: Only the class I devices with an asterisk (*) are also exempted from the GMP regulation, except for general requirements concerning records (820.180) and complaint files (820.198), as long as the device is not labeled or otherwise represented as sterile.
Class II Devices
The Food and Drug Administration (FDA) has also published a list of class II (special controls) devices (those devices are annotated as "(II)"), subject to certain limitations, that are now exempt from the premarket notification requirements under the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). FDA believes that these exemptions will relieve manufacturers from the need to submit premarket notification submissions for these devices and will enable FDA to redirect the resources that would be spent on reviewing such submissions to more significant public health issues. FDA is taking this action in order to meet a requirement of the Modernization Act. Class II devices are annotated "(II)". Please note that class II devices are NOT exempt from GMP requirements.