Open Letter to Manufacturers of Class III Devices
If your company makes one or more medical devices which the FDA has classified as Class III, you should ask the question: does each of my devices belong in Class III? Unless you are certain your devices belong in Class III, you may find it worthwhile to pay close attention to what follows in this letter.
A former FDA employee recently uncovered a scandal that the agency appears intent to cover up. This letter is intended to alert manufacturers of devices that have been misclassified into Class III how this may have happened and what they can do about it.
A Simple Test to See if a Device Was Misclassified
To see if this discovery applies to any Class III device your company makes, you need only answer the following questions:
1) Is the device life-sustaining or life-supporting? (Yes or No}
2) Is the device for a use which is of substantial importance in preventing impairment of human health? (Yes or No)
3) Does the device present a potential unreasonable risk of illness or injury? (Yes or No)
If the answer to all three questions is an unequivocal “No” your device has been probably been misclassified! There is a possibility that the FDA will reclassify the device to Class I or Class II – but you probably would have to battle to get the agency to make the change.
First, you need to understand what the former FDA employee uncovered in February, 2012.
The Crux of the Matter
The Medical Device Amendments authorized the FDA to regulate the medical device industry. Central to this program was the classification of medical devices into three classes: Class I General Controls, Class II (originally Performance Standards, now Special Controls), and Class III Premarket Approval. Over 5800 types of device have been classified; approximately 450 of these are in the most stringent Class III.
Each of the three classes is defined in the law.
The definition of Class III in the Federal Food Drug and Cosmetic Act appears at Title 21 U.S.C. § 360c(l)(C) which states the following:
“(C) CLASS Ill, PREMARKET APPROVAL-A device which because-
(i) it (I) cannot be classified as a class I device because insufficient information exists to determine that the application of general controls are sufficient to provide reasonable assurance of the safety and effectiveness of the device, and (II) cannot be classified as a class II device because insufficient information exists to determine that the special controls described in subparagraph (B) would provide reasonable assurance of its safety and effectiveness, and <-NOTE "AND"
(ii)(l) is purported or represented to be for a use in supporting or sustaining human life or for a use which is of substantial importance in preventing impairment of human health, or (II) presents a potential unreasonable risk of illness or injury, is to be subject, in accordance with section 360e of this title, to premarket approval to provide reasonable assurance of its safety and effectiveness.”
It is important to recognize that the definition has two parts, both of which must be satisfied for a device to be in Class III. Let us focus on the second part.
To be in Class III, at least one of the three following conditions must be satisfied:
The device -
1) "is purported or represented to be for a use in supporting or sustaining human life" OR
2) "is for a use which is of substantial importance in preventing impairment of human health" OR
3) "presents a potential unreasonable risk of illness or injury."
The statute is the ultimate authority for the definition of class III.
(It is worth mentioning that the definition of Class III at 21 CFR 860.3(c),(3) while worded differently still accurately captures the meaning and intent of the statute.)
The FDA has used a form for decades to assist in the determination of the appropriate classification of each type of medical device. The form, called the General Device Classification Questionnaire, is defined at 21 CFR 860.3(f):
“(f) Classification questionnaire means a specific series of questions prepared by the Commissioner for use as guidelines by classification panels preparing recommendations to the Commissioner regarding classification and by petitioners submitting petitions for reclassification. The questions relate to the safety and effectiveness characteristics of a device and the answers are designed to help the Commissioner determine the proper classification of the device.”
The text of the form was first published in the Federal Register in 1975, well before the enactment of the Medical Device Amendments, and again in 1977. Subsequently, the Classification Questionnaire was designated as Form FDA 3429. It has evolved over the decades into something very different from the one published in 1977. There have been several versions just since 1997. Under FDA policy, these changes were not announced in the Federal Register, nor was the public invited to comment.
All versions since 1997 (and probably much earlier) until June 30, 2012, have contained a serious logical flaw: devices that do not meet the second part of the definition of Class III are directed to Class III if the answer to question 6 is “No.” The figure below shows the first six questions of Form 3429 for the version effective June, 2012, which was renewed for 37 months effective June 1, 2012.
January 8, 2013
For the moment, ignore the areas marked in orange.
You can test the form yourself by answering the first three questions "No." As noted above, such a device would not meet the definition of Class III in the statute. However, If the answer to question 6 is "Yes" the device is directed to Class III. The logical flaw should be quite obvious.
Only a month after the form was renewed, CDRH revised it effective July 1, 2012. The revisions were to remove question 4 and the logical instructions in column 3, as marked in orange.
As you can see, the form no longer indicates the appropriate class. Moreover, the form has been rendered useless for its intended purpose!
These changes were made to counter the criticism in a Citizen Petition (Docket No. FDA-2012-P-0493).
Changing the form does not undo the damage of the past.
[4/19/13: Strike the following sentence: ]
I am certain that devices were misclassified into Class III because of the logical flaw that has existed in the Classification Questionnaire for many years.
In addition, anyone seeking reclassification of a device was forced to submit a completed Form 3429 - which was flawed as demonstrated above!
What Can You Do?
If you have already submitted a Premarket Approval application and it has been accepted by the FDA, congratulations! This may give you a marketing advantage over potential competitors. But if your Class III device is among the stragglers now being called up, you should consider filing a petition to reclassify if your device does not satisfy the definition of Class III.
If you believe your device was misclassified into Class III and you think it would be to your advantage to get it reclassified into Class II or even Class I, consult your legal advisor. You should be able to submit a petition to reclassify the device.
A Citizen Petition (Docket No. FDA-2012-P-0747) has appealed to the Commissioner to examine the alleged misclassification of devices into Class III because of the logical flaw in Form 3429.
Click here to view the Petition.
On January 4, 2013, the FDA sent out an interim response which said "FDA has been unable to reach a decision on your petition because it raises issues requiring further review and analysis by agency officials."
One can guess what these "issues" are and why the FDA is reluctant to acknowledge this goof. Stay tuned.
FDA granted my petition in a letter dated March 4, 2013 and signed by Nancy Stade. The agency acknowledged that Form 3429 needed to be revised, but rejected the idea that the Form itself was responsible for any misclassifications. I realize that I attached too much importance to Form 3429. In fact, we do not know the exact wording of the Classification Questionnaire in use at the time many of the device classifications were done. FDA's process for classifying was internal to the agency and details aren't available.
HOWEVER, I MAINTAIN THAT A DEVICE WHICH DOES SATISFY AT LEAST ONE OF THE THREE CONDITIONS CITED ABOVE DOES NOT QUALIFY FOR CLASS III.
The fact that the FDA granted my Citizen Petition FDA-2012-P-0747 and revised Form 3429 shows that agency personnel were biased towards Class III for years.
To read the March 4th letter, click here.
In the second paragraph, the letter stated "FDA has investigated Form FDA 3429 and has determined that changes should be made to more closely align the form with section 513(a)(1)(C) of the Federal Food, Drug,and Cosmetic Act (FD&C Act)."
On page 2, the letter states "FDA has changed Form FDA 3429 to remove the information in the last column and the row enumerated four."
The revisions, as explained above, were made effective July 2012. Actually, the memorandum to OMB listing the revisions and justifying them was dated July 24, 2012 and, according to the Publications Support Center of HHS, the request to revise the form was received on Sept. 6, 2012.
I find it strange that CDRH acted so quickly to revise Form 3429 but took so long to respond to the petition. The petition was filed on July 10, 2012, but the revised form was effective July 1, 2012 - 9 DAYS BEFORE THE PETITION WAS FILED! CDRH took 7 months and 22 days to respond to my petition. So much for openness.
Leroy L. Hamilton, Ph.D.
January 8, 2013
minor revision January 15, 2013
second revision February 4, 2013
third revision April 19, 2013