FDA Warning Letter to Dexcom

Note the sensor fractures have been discussed on the CWD forums here: http://forums.childrenwithdiabetes.com/showthread.php?t=50819&highlight=maude

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm213414.htm

Dexcom Inc

Department of Health and Human Services
Public Health Service
Food and Drug Administration
Los Angeles District
Pacific Region
19701 Fairchild
Irvine, CA 92612-2506
Telephone: 949-608-2900
FAX: 949-608-4415
WARNING LETTER
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
May 21, 2010
W/L 21-10

Mr. Terrence H. Gregg, President and CEO
DexCom, Inc.
6340 Sequence Drive
San Diego, CA 92121
Dear Mr. Gregg:
During an inspection of your firm located in San Diego, California on January 11, 2010 - February 8, 2010, an investigator from the United states Food and Drug Administration (FDA) determined that your firm manufacturers the Seven PLUS Continuous Glucose Monitoring System ("Seven PLUS CGMS") (Class III). Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 USC 321(h)], these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.
This inspection revealed that your Seven PLUS Continuous Glucose Monitoring System devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. 360i, and 21 C.F.R. Part 803 - Medical Device Reporting (MDR) regulation. Significant deviations include, but are not limited to, the following:
Failure to submit MDR reports within 30 days of receiving or otherwise becoming aware of information that reasonably suggests that a marketed device has malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur as required by 21 CFR 803.50(a)(2).
Specifically, the firm failed to submit MDR reports to the FDA for complaints involving sensor wire fractures underneath patient's skin as exampled by:
1. Customer Report: 09-5141, dated 7/11/2009 reported a sensor wire broke off in a three (3) year old and reported a piece of it was under her skin. The mother reported the child had surgery under general anesthesia to remove the broken wire underneath her skin.
2. Customer Report: 09-0274, dated 1/6/09 reported the sensor wire tip broke off in patient's body. The DexCom representative advised patient to not to pursue extraction. The report states "sensor break with fragment retained under the skin".
3. Customer Report: 09-3516, dated 5/07/09 the report states (that when) the nurse went to pull the old sensor off the sensor wire it was not there. The patient's nurse reported she could see it under the skin but she could not get hold of it with tweezers and then it disappeared. The nurse thinks "it came off and is still in his skin. "
4. Customer Report: 09-3641, dated 5/18/09. Patient reports 2 sensors have broken off under his skin. His most recent sensor looks broken upon removal today, and he can feel the wire under his skin. Site is red and he is going to prescribing physician.
5. Customer Report: 09-5555, dated 7/20/2009. Patient called (to) report a failed sensor and has irritated skin. Patient reported he thought the wire came out completely, but his doctor removed a "hair like structure" from under his skin.
6. Customer Report: 09-4237, dated 6/17/2009. Patient is a 30 month old child. Mother called to report sensor wire breakage under skin of child. Patient taken to the ER when an infection developed.
We have reviewed your response and have concluded that it is inadequate.
Your response dated March 2, 2010 stated that you have agreed to submit sensor wire fractures as MDRs going forward for all complaints of fractured wires received after January 1, 2008. You stated that seventy-three MDR reports were to be filed for all complaints; however, the evidence collected during the establishment inspection documented that you group multiple events within anyone complaint which indicates that there are likely more than 73 individual complaints of fractured sensor wires. Each event should be reported as an individual event under Medical Device Reporting. You also stated that your MDR review and reporting procedures were revised and training completed. However; documentation of the review and procedures was not provided in the response.
Additionally, evidence collected during the inspection documented that your firm knows and has knowledge of facts that give notice that your device introduced into interstate commerce is being used for conditions, purposes, and uses other than the ones for which it is offered (ie. Qff-label use in pediatric patients and use in body locations other than the abdomen). Under 21 CPR 801.4 you are required to provide adequate labeling for such a device which accords with such other uses. We believe that the off-label use of your device in pediatric patients and use of the device in locations of the body other than the abdomen (which appears to be correlated with the incidence of sensor probe fractures requiring medical intervention) require action from you in accordance with this regulation.
We are recommending that the firm add additional Warning and Precaution statements to the labeling, the patient education brochure, and the website as follows:
? Under the Warnings section, warn the user: (1) not to remove a retained sensor probe distal segment, unless it is clinically indicated; and (2) to contact the health care provider for medical advice in the event of a sensor probe fracture.
? Revise the Precautions bullet to state: The SEVEN and SEVEN PLUS Systems are not approved for use in children or adolescents, pregnant women or persons on dialysis, and move this bullet to the Warnings section.
? Add a Limitations of Use section to reiterate the above warning: The SEVEN and SEVEN PLUS Systems are not approved for use in children or adolescents, pregnant women or persons on dialysis, and move it to the Warnings section.

? Under the Warnings section, include the following statement: The safety and effectiveness of the SEVEN and SEVEN PLUS Systems have not been evaluated for sensor probe insertion in sites other than in the skin of the abdomen.
You should take prompt action to correct the violation(s) addressed in this letter. Failure to promptly correct these violation(s) may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies are advised of the issuance of all Waming Letters about devices so that they may take this information into account when considering the award of contracts.
Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violation(s), or similar violation(s), from occurring again. Include documentation of the corrective action you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.
Your response should be sent to:
Acting Director, Compliance Branch
Food and Drug Administration
19701 Fairchild
Irvine, CA 92612-2506
If you have any questions about the content of this letter please contact Dr. Raymond W. Brullo, Compliance Officer at (949) 608-2918.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violation(s) at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violation(s) noted in this letter and in the Inspectional Observations, Form FDA 483 (FDA 483), issued at the closeout of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality assurance systems. You should investigate and determine the causes of the violation(s), and take prompt actions to correct the violation(s) and to bring your products into compliance.
Sincerely yours,
/S/
Alonza E. Cruse
District Director

 

Dexcom investor conference call in response to the letter: http://investor.shareholder.com/dexcom/eventdetail.cfm

I took some notes from the call:



Seven and Seven+ are not approved for children under 18, and recommends the abdomen area - only has been tested in adults, not tested in children, adolescents, pregnant or on dialysis. Dexcom feels the labeling was ok but will work to approve the revised labeling

Q&A
% of sales to pediatrics? - Dexcom doesn't have that metric and will avoid answering

Status of getting pediatric indication? will submit for pediatric in the fall for gen 4

Why you would or would not disclose the warning letter?
Dexcom says they received it late last week and operationally this was the first day they could respond.

Did you have a sense this was coming? No. But as part of the MDR reporting issue Dexcom said they complied and felt they adequately answered their question and interpretation of reporting requirment

Any belief physicians would change indication? Dexcom does not promote off label use of the product and they adequately label the product.......Dr. Garg did a trial with alternate site use...but it wasn't sponsored by Dexcom and didn't expect to submit it

Gen4 trials are still on the abdomen

Any change of the wire between Gen3 and Gen4? We're constantly trying to improve the product so trying to increase the strength of the Gen4 sensor wire. A lot of great attributes in the new product design including its performance

For the Gen4 any more appropriate for pediatrics? No - other attributes that came along made it more appropriate for pediatrics

Any reason why it fractures more not in the abdomen? Dexcom says they just tested it in the abdomen and that's what it's labeled for....

Maude data base weren't able to locate any other reports of sensor fractures from competition....commentary? No idea.

Will you do anything different with your approach to reporting fractures? No way to know this - When we filed 7 PMA there were conversations with the agency that the competitors both had experiences with sensor fractures. At that point we had had zero. When we submitted PMA, we reported fractures...they ultimately approved.

Days usage - correlation with days of used w/fracture rate? None whatsoever.

How will your sales force will respond, how competition will respond....? I have high degree of respect for the agency...our competitors will have the same landscape and look at what they're doing and pump level & there have been SMBG advisory meetings....the incidence is 3/10,000 sensors distributed. It's de minimis in terms of the percentage and we're improving the fatigue factor in gen4- we're still the best performing, easiest to use, most accurate in hypoglycemia detection. We'll respond to agency, change labeling to meet their suggestions. We're not addressing it in any more need than it needs to be addressed.

With the labeling change - if you don't have the labels in time, can this impact supply for customers at all, will there be any write offs associate? No and No. We will file a submission with the appropriate language. ....right now it's biz as usual

They wouldn't make you stop distributing until you relabel? There is nothing in the letter that indicates that. They are just asking to make it more visible in the labeling

Of the fractures how many were outside the abdomen? You're now getting to a degree we prefer not to comment on.

Hi Terry I think it was a pretty mild warning letter as far as warning letters go. Do you think you'll do a study on pregnant women and where do they put the device? There are two pregnancy studies, enrollment has been slow - researching for both gestational and t1d. It's a valuable tool but we have 2 sites that are ongoing. I can't give you an estimation about when the studies will conclude.

Are those women able to put it on their abdomen? It's moved back a bit - think of the love handles....

On the wires themselves, if they do break does the patient get an alert? Yes you lose communication. Quite frankly the recommendation is not doing anything. It's like a splinter.

Their warning letter talked about the worst of them...in the vast majority, they can just remove with tweezers right? Either that or just let the body expel it - that comes from experience and surgeons who have identified it....everybody tells us the same thing leave it alone.

Looking at the letter - can you explain the grouping of the events and the suggestion there are more than 73 complaints? That portion of the FDA letter is in error...there were not grouping of multiple complaints under one complaint, we corrected that while inspector was on site. 73 was the number in totality from 2008-March 2010.

Complaints preceding 2008? "We haven't disclosed that information and we're not going to."

 

I know we've had a couple of people on here who have had the sensor break off inside the body, but I don't think anyone had any lingering problems with it.

Sounds to me like the FDA isn't requiring a redesign, but just more warnings?

 

It would freak me out if the sensor broke off in my skin. Like, a lot.

I don't think that would happen with the MM CGMS, though, because the sensor wire is huge. The idea makes me squirm. It wouldn't put me off using the CGMS, though, because it seems pretty rare that it causes a problem.

 

Yeah, but on the flip side it happens with syringe needles fairly often.. likely more often than with the sensors, and the general advice is to leave those in. It totally wierds me out, but I can see why - unless there is an infection the risks are greater with removing any kind of foreign object that small than just leaving it alone.

The gist of what I get from this letter though, is that the FDA is unhappy with what seems like a large amount of "off-label" usage by customers... in terms of both pediatric usage (which it is not approved for) and other body areas besides the abdomen. I don't really get how improved labeling is really going to change that?

 

I did not know that. I would have freaked out if I would have broken off a needle in Jack when we were on MDI!

Yeah, I don't get why the FDA is all hot and bothered about that either. It happens all the time with all sorts of devices and drugs. You'd think a CGM used off-label would be pretty far down their list of things that could be harmful. (Plus, both the MM and the Nav are prescribed off-label all the time too.)

 

Has Dexcom customer service asked anyone here when the receiver couldn't receive a signal, if the wire they took out was shorter than a new one?

See Elizabeth Arnold's Tweets last night about her experience Tweets are newest on top, oldest at the bottom so you will want to read from the bottom to the top:

http://twitter.com/ElizabethArnold

asked me to check the size. (About 2cm had broken off.)

sensor wire from a sensor that worked. I never would've noticed the wire was inside me if the Dex rep hadn't

I'll just say, next time a sensor fails to start, take it out & compare the size of the wire w/ the size of a

Dex said it would eventually come out on its own, but it's been months already, so we'll see...

Yes, I'll definitely still use it (unless someone says it's hazardous to have a wire forever stuck in my

me to check...

failures I had were because of breakage. Didn't hurt or anything...Like I said earlier I wouldn't have known if Dexcom didn't ask

Yup...They broke off halfway. Next time you have a sensor fail to start, take a look to see if the wire's shorter. 2 out of 3

Fact Dex asked me leads me to believe wire breakage is A LOT more common than they let on. k

Never got an infection, never would've even noticed if Dexcom hadn't asked me to check the wire!

issues) since I've had 2 wires break off in my arm, never to be seen again...

It's still worth it, IMO, but I'd like to hear more about the potential for infection (or other

 

I believe they are being told specifically to revise their labeling to exclude pediatric use. Could this have an effect on insurance coverage?

 

From what I have heard, the risks are minimal unless you reuse needles. I certainly only heard about needles breaking off as a horror story to put me off using them more than once, and it worked! That said, I have a friend who changes her novolog pen needle only once per day, so that's the same needle for 3-5 shots, and she's been doing this since she was 4 (she's now 15) and has never had a needle break off.

 

Really? What type of needles?

I'm curious because, my dd began with shots and we moved to MDI for a year and a half before pumping. I went through boxes and boxes of needles. I will still cover some high BGs using a syringe and I've never had one break off while doing an injection.

 

6 years of 2 injections per day between 1989-1995 and never had a BD Syringe needle break off in the skin...not once.

 

I think they wouldn't be making a big deal about the off label usage if they weren't seeing the sensors breaking they way they are.. and in other parts of the body other than the abdomen.. I never even looked to see where the MM CGMS is approved for.. it works well for us in the arm, so I never bothered to look at that info.. We did use MM cgms off label, Kaylee was 4 when we started to use it (FDA approved for 7 and up).. but we also used lantus off label (approved for 4 and up) and she was 35months old.

So, my guess is they are all hot and bothered by the fact that they are breaking and being used else where than what its FDA approved.. If the sensors weren't breaking they probably really wouldn't care.

 

Neither have I (I don't usually reuse mine, which I think GREATLY increases that risk), but I have certainly heard of more of this happening than sensor wires breaking.. and it too is most likely linked to "off-label" usage (in this case reusing for multiple injections).

I've been "warned" about it enough by every endo and CDE I've ever seen.. to suspect that they see it pretty often in people who habitually reuse needles.. especially with today's 31g (and thinner) needles.

 

I've never heard of this... And neither the endo or the cde has ever mentioned anything about it possibly happening.. I have often wondered if it COULD happen..and the thought of it happening, syringes, pump sites, or sensors, scares the crap out of me and gives me the heebe geebes.

 

I was thinking the same thing.

 

that would suck cause you know insurance would be doing a happy dance if they don't have to pay for such things.
As for needles-we've had one break while injecting air into a bottle, it was a walgreens brand I believe.

 

I remember those zoomed in pictures of how a needle looks after one use, six uses, trying to warn you not to reuse, and what I got from that was, little bitty parts of the needle break off after each injection.

While using the Guardian, I had two sensors whose probe broke when I was taking it out and I'm not sure I got them totally out, however, both had been in me for way past the recommended three days.

 

Considering its not FDA approved for under 18 right now, and MOST insurances are paying for it without to many questions I'm not sure it would have a great impact that way... UNLESS the FDA sent something out.. or if the dr could get in some sort of 'trouble' for writing a prescription for off label..


Didn't someone here actually try to talk to dexcom about a younger child and dexcom wouldn't give them any information because it wasn't FDA approved for children? This was a little while ago, if I remember correctly.

 

I had a sensor failure last week. I was specifically asked if the wire was still attached to the sensor when I removed it. (It was.) This was the first time that I had been asked that question and it caught me a bit off guard. I guess I now have an idea as to why they asked.

 

I believe there's a difference between the label specifically excluding pediatric use and "not approved" - well, there must be or the FDA wouldn't have their panties all in a wad over the issue.

Of course I'm speculating but it might also impact the liability of a doctor prescribing it. I have a doctor friend who I can ask.