Fresenius warning

[obsidianom]

I just got an update from MedScape which gives constant news in the medical field to physicians.
Fresenius just was warned by the FDA to clean improve the way it sterilizes dialysis blood filters.
That is something to really think about . Very scary since many clinics and home patients use their machines and filters.


'In March the company's separately listed subsidiary Fresenius Medical Care, the world's largest dialysis company, was told by U.S. regulators to improve the way it sterilizes certain dialyzers for filtering patients' blood.'
(i pasted this from the article)

Nice touch Fresenius!   

   

[rocker]

I'm gonna take a real wild guess here...

The way they're doing it now is much less safe....and slightly cheaper.

Amiriteamirite??

[Rerun]

Both top companies are treating us Third World.  They don't give a crap.  What a gig.  Keeping people alive to make them money and if they get problems or complaints they just dismiss them and they will soon, very soon go away.

OMG!

[Dman73]

I didn't think that they did reuse anymore...

[obsidianom]

I didn't think that they did reuse anymore...

I beleive this is about the initial sterilization process for the filters after they are manufactured. They have to be sterilized before use even when new. That is very scary when a company is warned about its sterilization practices.

[jeannea]

My problem is it is not clear what they were warned about. I worked in pharmaceuticals. The FDA comes to medical device companies and pharma companies and dialysis centers (well maybe the state does the centers) and inspects them. Was there flaking paint on the wall? Did they not have their procedures written down properly? Did someone not sign a page of a batch record? Or is the product really not sterile? There are sooooo many rules and laws that everyone gets a list of what they're doing wrong. The question is how serious was the violation? Was it a constant problem? I know it's scary to hear about this but in most cases the inspection and warning leads to at least some improvement. Unfortunately no procedure is ever perfect since we're human but we do better in the US than some places.

[Ninanna]

Here is there warning letter from the FDA

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm344711.htm

March 5, 2013
WARNING LETTER
 
 
UPS Overnight
 
Robert M. Powell
CEO & Deputy Chairman
Fresenius Medical Care, North America
920 Winter Street
Waltham, MA 02451
                                                                                                Ref: DEN-13-10-WL
Dear Mr. Powell:
 
During an inspection of your firm located in Ogden, UT on November 26 through December 7, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Optiflux Polysulfone Dialyzers.  Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 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 to affect the structure or any function of the body.
 
This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.
 
We received responses from Brian R. Burns, Senior Vice President, Quality Systems and Regulatory Affairs North America (Waltham, MA) dated December 28, 2012, January 2, 2013 and February 7, 2013, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
 
1)    Failure to establish and maintain adequate procedures for verifying the device design. Design verification shall confirm that the design output meets the design input requirements, as required by 21 CFR 820.30(f).  For example:
 
a.    The design input for the (b)(4) dialyzers required biocompatibility of these dialyzers be no different than the (b)(4) dialyzers.  However, the biocompatibility testing determined that the (b)(4) dialyzers (b)(4).  The biocompatibility studies concluded that additional testing was required to quantify the amount of (b)(4) delivered to the patient and to evaluate the effect of the (b)(4) on the dialyzer membrane.  During the inspection, you failed to provide documentation demonstrating that the additional testing was conducted prior to releasing the (b)(4) dialyzers in 2001.
 
b.    Your study (b)(4).  During the inspection, however, you reported that the (b)(4) dialyzer complaints were mainly associated with (b)(4). No testing was conducted for (b)(4), including (b)(4).
 
We have reviewed your responses dated 12/28/2012, 1/2/12013 and 2/7/2013, and do not find them to be adequate.  Your design verification studies are incomplete.  For example, the design verification testing report (b)(4), did not discuss deviation notices cited under reference #s 14-16. Your design validation/verification procedure, SOP 07E-010A, dated 09/24/90, does not mention how the verification studies are conducted.  None of the studies submitted as part of your responses quantified an acceptable level of PVP residual after priming.  You failed to provide justification for only using (b)(4) dialyzers for comparison in your design verification studies; the (b)(4). The aforementioned responses also failed to provide a summary of your firm’s studies and test reports regarding non-complement mediated dialyzer reactions.   
 
Furthermore, your updated biocompatibility testing, (b)(4), did not address whether or not platelet adsorption was assessed, and your design validation report, dated 12/27/00, did not evaluate the effect of (b)(4) dialyzers on platelet adhesion. Additional testing, completed in 2001 under study (b)(4). 
 
2)    Failure to establish and maintain adequate procedures for validating the device design. Design validation shall be performed under defined operating conditions on initial production units, lots, or batches, or their equivalents. Design validation shall ensure that devices conform to defined user needs and intended uses and shall include testing of production units under actual or simulated use conditions. Design validation shall include software validation and risk analysis, where appropriate, as required by 21 CFR 820.30(g).  For example:
 
a.    The design validation for the (b)(4) of Optiflux Polysulfone (PS) dialyzers (b)(4) is incomplete.  A clinical study, (b)(4), was conducted (b)(4). The study indicated that (b)(4).  The study was conducted approximately (b)(4)  the dialyzers were released for distribution in 2001. Furthermore, you were not able to provide documentation demonstrating that the study was conducted using (b)(4).
 
We have reviewed your responses dated 12/28/2012, 1/2/12013 and 2/7/2013, and do not consider them to be adequate.  The responses indicated that the clinical trial results (b)(4).  However, the clinical trial was conducted under (b)(4).  Therefore, this clinical trial constituted design validation activities for the (b)(4) dialyzers.  See also the comments regarding design validation/verification and evaluation of platelet adhesion under #1 above.
 
b.    Your 10/31/12 Risk Management Matrix (RMM) failed to identify risks per RMM protocol, S100429-01, Rev. D, dated 9/28/12.  Specifically,
 
i.  Your dialyzer R&D test report (b)(4) concluded that (b)(4).  The report also stated that (b)(4).  However, your 10/31/12 RMM failed to assess risks due to (b)(4) of the (b)(4) dialyzers.
 
ii.  Your membrane surface characteristics/chemistry study, dated 4/19/12, (b)(4).  However, your 10/31/12 RMM failed to include the risks resulting from (b)(4).
 
We have reviewed your responses dated 12/28/2012, 1/2/12013 and 2/7/2013, and do not consider them to be adequate.  The responses indicate that the RMM (Rev. A, dated 10/31/2012) references (b)(4)  This response does not address risks of increased residuals associated with the process which are independent of raw material or components that do not meet specification upon receipt. For example, the RMM did not consider the fact that raw materials, (b)(4), can contribute to risks even if the materials meets specification.  Furthermore, none of the studies provided for review evaluated the risks associated with (b)(4) Optiflux PS dialyzers under actual or simulated use conditions.
 
Your firm should take prompt action to correct the violations addressed in this letter.  Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice.  These actions include, but are not limited to, seizure, injunction, and civil money penalties.  Also, federal agencies may be advised of the issuance of Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices to which the Quality System regulation violations are reasonably related will not be approved until the violations have been corrected.  Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.
 
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again.  Include documentation of the corrections and/or corrective actions (including any systemic corrective actions) that your firm has taken.  If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities.  If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address all violations included in this Warning Letter.
 
Your firm’s response should be sent to: U.S. Food and Drug Administration, Denver District Office, Building 20 – DFC, P.O. Box 25087, Denver, CO 80225-0087, Attn: Sarah A. Della Fave, Compliance Officer.  If you have any questions about the contents of this letter, please contact Ms. Della Fave at 303.236.3006.
 
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility.  It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA.  The specific violations noted in this letter and in the FDA 483, List of Inspectional Observations, issued at the close of the inspection, may be symptomatic of serious problems in your firm’s manufacturing and quality management systems.  Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance.
 
 
Sincerely yours,
/S/                                                                                               
LaTonya M. Mitchell                                       
District Director
Denver District                       

I didn't see anything about sterilizing filters however.

[jeannea]

To be honest, that letter looks really standard and does not alarm me. They need to some more documentation to the batch record and produce a few more validation lots. I can see where it would seem alarming when people read it, but it's part of the dance that companies do with the government. It also appears to only one type of dialyzer. I don't know how many types they manufacture and sell. The company tries to make as few validation batches as possible to save money. The FDA worker tries to look like he's doing his job by pestering them. The first and maybe second response by the company would have been "we already showed you that look on page 316 section 3.6.A" or whatever. I don't want to dismiss concerns but I'd be more concerned what happens in your clinic than in the plant. The manufacturer eventually does enough to satisy the FDA or they get shut down like the big Tylenol plant in Fort Washington PA.

[obsidianom]

We have reviewed your responses dated 12/28/2012, 1/2/12013 and 2/7/2013, and do not find them to be adequate.  Your design verification studies are incomplete.  For example, the design verification testing report (b)(4), did not discuss deviation notices cited under reference #s 14-16. Your design validation/verification procedure, SOP 07E-010A, dated 09/24/90, does not mention how the verification studies are conducted.  None of the studies submitted as part of your responses quantified an acceptable level of PVP residual after priming.  You failed to provide justification for only using (b)(4) dialyzers for comparison in your design verification studies; the (b)(4). The aforementioned responses also failed to provide a summary of your firm’s studies and test reports regarding non-complement mediated dialyzer reactions.   
 
Furthermore, your updated biocompatibility testing, (b)(4), did not address whether or not platelet adsorption was assessed, and your design validation report, dated 12/27/00, did not evaluate the effect of (b)(4) dialyzers on platelet adhesion. Additional testing, completed in 2001 under study (b)(4). 

PVP  is polyvinylpyrrolidone or POVIDONE which is used in disinfecting dialysis membranes/filters.
The U.S. Food and Drug Administration (FDA) has approved this chemical for many uses,[14] and it is generally considered safe. However, there have been documented cases of allergic reactions to PVP/povidone, particularly regarding subcutaneous (applied under the skin) use and situations where the PVP has come in contact with autologous serum (internal blood fluids) and mucous membranes

I see there are some issues here as PVP can cause allergic reactions. It sounds like they never made the test results public for REACTIONS to PVP ."Non _complement mediated dialyzer reactions" which would be allergic immediate reactions. THESE CAN  KILL. They didnt deal with "acceptable levels "of PVP after priming the filter.
How much remains to enter your blood and possibly set off an allergic response and ANAPHYLAXIS.

Also Platelet adhesion would be an important test on these membranes. You dont want platelets sticking to the membranes and clotting.

I dont see this as just a minor FDA harrassment. yes it is written in Government speak but it still makes some very valid points that need to be adressed.

[jeannea]

That wasn't in the other letter. I'm sure they will have to test for Povidone in the lab. The thing I'm still not clear on is if these are dialyzers already being sold or a new product that has not been approved for sale yet. To me it appears to be a new product but I can't be sure.

[obsidianom]

"During the inspection, you failed to provide documentation demonstrating that the additional testing was conducted prior to releasing the (b)(4) dialyzers in 2001."



"This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. ''




I think this answers your question. These dialyzers have been manufactured since 2001.  This is NOT a new product.

In addition the FDA found the devices are ADULTERATED in the way they are manufactured. This is not just a paperwork problem.

[jeannea]

Adulterated is the word for any problem. Are they really issuing a warning now for a lack of testing in 2001? This is odd and I don't think we can figure out the level of danger involved here. I suppose you could call their PR dept and ask for a reply or call the FDA and ask but I suspect you'll get more jargon than anything. What we have here is a big lack of info.

[jeannea]

And I'm really sorry. In my old life I could find the progression of letters on the FDA website, put them in order, and try to figure out what the actual issue is. Unfortunately I had an encephalitis that really affected me. I don't think I can accomplish that anymore. I wish I could. Try not to panic every time the FDA issues a warning letter. They issue hundreds.

[obsidianom]

Whatever is going on , Fresenius needs to do the right thing . These are life saving and can be life taking devices. None of us can see into their manufacturing plant and know what is going on , but the fact they are in trouble is a scary thing to anyone who uses their products.

[Dman73]

I don't think that any of the other dialysis providers offer a safer environment as I believe it is a industry wide problem.

I am more concerned of 1 tech watching 5 patients while the others are on break. The other day we had a power outage due to a thunder storm and it took a while before the tech received help. After things quieted down I told them how comforting it was sitting on a machine that was not working. They brushed off my comment and it is no wonder that they do not allow photography or recording in their facility.

Things won't change unless a catastrophe occurs, the patient must endure, such is life in the D world.

[Simon Dog]

I don't think that any of the other dialysis providers offer a safer environment as I believe it is a industry wide problem.

I am more concerned of 1 tech watching 5 patients while the others are on break. The other day we had a power outage due to a thunder storm and it took a while before the tech received help. After things quieted down I told them how comforting it was sitting on a machine that was not working. They brushed off my comment and it is no wonder that they do not allow photography or recording in their facility.

Things won't change unless a catastrophe occurs, the patient must endure, such is life in the D world.

Pull the handle off the back of the machine, open the door., flip the lever out, attach the crank, set up for saline flush and crank the blood back into yourself at between 6 an d10 RPM (assuming a 2008K or similar machine).

That will definitely get their attention.