Difference Between 510(k) and PMA

Should a medical device manufacturer has a class III device and it has to file for a Premarket Approval (PMA). PMA is basically a FDA process of scientific and regulatory review to evaluate the safety and effectiveness of the Class III medical devices. And PMA is the most stringent device marketing application required by FDA because of its inherent risk and safety of the device. FDA will approve a PMA if the sponsor demonstrated sufficient and valid scientific evidence to assure the device is safe and effective for its intended use or uses.

Examples of Class III medical devices are implantable pacemaker, pulse generator, HIV diagnostic test, automated external defibrillators (AED) and spinal cord stimulator.

Example of Automated External Defibrillators (AED) is shown below:

                                         Courtesy of www.heartstart.com

Several important differences between PMA and 510(k) submission are the cost, time and the requirement of clinical trial data. Since PMA has a higher risk and warrant the most stringent scrutiny⁽¹⁾ from the agency like risk management and manufacturing control.

Overview of the differences between a PMA and a 510(k) FDA submission is summarized in the table below:

Differences	510K Submission	PMA Submission
Class of Device	Generally for Class II and pre-amendment Class III(2).	Generally for Class III(1).
Predicate Device to demonstrate substantial equivalence	Yes.	Yes.
Clinical Study	Generally A Clinical Trial is not required.	The requirement of clinical study which might take 1 – 2 years.
Review Time	̴ 90 days. But, in reality, it is usually takes longer than 90 days.	An average of 1 year.
Application Fee for FY2013(October 1, 2012 through September 30, 2013)	Standard Fee is $4960 and fee for small business with ≤$100 million in gross receipts or sales is $2480(3).	Standard Fee is $280K. Fee for small business is $62K(3).

1. --- Premarket Approval (PMA), FDA website, www.fda.gov, Updated as of 01/24/2012.
2. --- 21 CFR 58 Good Laboratory Practice For Nonclinical Laboratory, CFR 21, Volume 1,
      April 1, 2012.
3. ---Premarket Notification 510(k) Review Fees, FDA websites, www.fda.gov, dated
      09/28/2012.

How to Prepare and Submit a Traditional 510(k)?

Typically, Medical Device Manufacturer in the US has three types of Premarket Notification 510(k) to be submitted to FDA (1): Traditional, Special and Abbreviated. Special and abbreviated methods can only be deployed if certain criteria are met (1). The traditional 510(k) method can be used under any circumstances. It is a requirement under 21 CFR 807 Subpart E.

 When a sponsor need to file for 510(k), the regulatory department should always visit the FDA to ensure they have the latest guidelines and requirements. It also depends on the medical device technology and intended use of the device in question. This blog is for general knowledge of how to prepare and submit a 510(k), BUT in actual process, it will be much more detail and a lot of work required.

 The following is the ‘general’ and simplistic content and format of a traditional 510(k) to be submitted with a premarket notification.  Note: Not all content and format of a 510(k) are identical. Here is the general content and format. This is only for traditional 510(k). Sponsor should provide descriptive information about indication of use and technology, results of performance testing to demonstrate substantial equivalence. Sample is shown below (1).

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)    Table of Contents

6)    510(k)summary or 510(k) statement

7)    Truthful and Accuracy Statement

8)    Class II Summary and Certification

9)    Financial Certification or Disclosure Statement

10) Declarations of Conformity and Summary Reports

11) Executive Summary

12) Device Description

13) Substantial Equivalence Discussion. In this section, a detail comparison between the device to be marketed and the predicate device or devices. You can compare with only one or more than one predicate device.

14) Proposed Labeling

15) Sterilization and Shelf Life

16) Biocompatibility. It involves some biocompatibility testing and the testing report as well.

17) Software. Not all medical device has software. Software also has its own ‘medical device’ guidance to follow. We will discuss software in some other blogs.

18) Electromagnetic Compatibility and Electrical Safety. Not too many medical device manufacturers can afford to perform this type of testing. Usually, several samples will be submitted to third party testing outfit to be done.

19) Performance Testing-Bench. Submit the bench testing results.

20) Performance Testing-Animal. Submit the animal testing results.

21) Performance Testing-clinical. Submit the clinical testing results.

22) Others.

                    Where to Submit a 510(k)
 

A 510(k) should be organized in a temporary and inexpensive binder. It is not advised to bind all the documents for 510(k) because the reviewers might take the submission out for review (1). Paper size should be the usual 8.5 inches by 11 inches.

Two copies of the 510(k)s must be submitted and one of the copy must be electronic form. The address should be send to:

 Food and Drug Administration *
Center for Devices and Radiological Health
Document Mail Center - WO66-G609
10903 New Hampshire Avenue
Silver Spring, Maryland 20993-0002

 

1.—How to Prepare A Traditional 510(k), FDA websites, Page Last Updated:
   12/17/2013.

 2. Source; ---Guidance for Industry and FDA staff: Format for Traditional and
    Abbreviated 510(k), August 12, 2005, FDA, CDRH.

 

 

 

European Union Classification of Medical Devices

Basically, there are three broad types of medical devices per European Union classification and the three (3) types of Medical Device Directives are below.

The following are the three Medical Device Directive (MDD) for all type of medical devices (1) in European Union.

·       93/42/EEC- Medical Device Directive

·       90/385/EEC- Active Implantable Medical Device Directive

·       98/79/EC – In Vitro Diagnostic Medical Devices Directive(2)

 For medical device which fall into 93/42/EEC and 90/385/EEC, It is prudent for manufacturer to perform a formal device classification per Annex IX of the MDD. In annex IX, there are information to help sponsor to classify the product. Just follow them.

Per 93/42/EEC- Medical Device Directive &  90/385/EEC- Active Implantable Medical Device Directive, there are Non-Sterile Class I Non-Measuring, Sterile Class Measuring, Class IIa, Class IIb and Class III.

For medical devices classified from Sterile Class I Measuring to Class III, medical device manufacturers require the implementation of Quality Management System (QMS) in accordance to Annex II and V of 93/42/EEC (1). Most companies or sponsors will apply ISO 13485 standard to achieve QMS compliance. 

Note: ISO 13485 is akin to 21 CFR 820 required in the US market. Both quality systems have overlapping quality requirements. Therefore, it is not uncommon for medical device companies to comply with both.

In fact, many multinational like Johnson & Johnson (J&J), Boston Scientific and Siemens willl comply to more than ISO 13485 and 21 CFR 820. They will have to comply with each regulatory and quality compliance of that country in question where the product has to be sold. For example, if J&J wants to sell its products in Australia, the products will have to be in compliance with quality system stupulated by Australia TGA.

What is the documents need to be filed with European Union? For Non-Sterile Class I Non-Measuring to Class IIa, sponsors require to prepare a technical file, while for Class III, it is called Design Dossier.

There are a little difference between EU and USA in term of interphasing with regulatory agencies. In US, the sponsors will have to directly deal with the FDA, while in European Union, sponsors need to appoint an Authorized Representative located in Europe which is qualified to handle any regulatory issues. Then the EC REP shall be placed on the Insturction For Use (IFU) or outer packaging or device label (1).

 Another concept is the Notified Body, it is a third party accredited by the European authorities to audit the sponsor QMS, technical file or Design Dossier.

 After Notified Body ‘approved’ the technical file and design dossier, the sponsor will be issued a CE Marking Certificate for the device. The notified body will audit ISO 13485 of the sponsor manufacturing capability. Assuming the manufacturing the medical device is top notch, ISO 13485 certificate will be issued to the sponsor. The ISO 13485 certiifcate must be renewed every year. CE Marking certificate are generally valid for three years (1).

  

1.     ---European Union The Medical Device Regulatory Approval Process, Emergo Group Chart, 03/2014 Updated.