-----------------------------

From: Middendorf, Christopher (CBER)

To: Twyla Ramos

Cc: Middendorf, Christopher (CBER)

Sent: Friday, February 15, 2008 4:01 AM

Subject: Re: trace amounts of thimerosal

Dear Ms. Ramos,

Thank you for your recent  [recent? Ha! 3 months ago - TR]  inquiry to FDA's Center for Biologics Evaluation and Research (CBER) regarding thimerosal.

CBER, one of six centers within FDA, is responsible for the regulation of biologically-derived products, including blood intended for transfusion, blood components and derivatives, vaccines and allergenic extracts, and cell, tissue and gene therapy products.

In accordance with 21 CFR 610.2(a), samples of any lot of licensed product, together with the protocols showing results of applicable tests, may at any time be required to be submitted to the Center for Biologics Evaluation and Research (CBER) for review and confirmatory testing. CBER conducts directed testing for thimerosal in products when determined to be appropriate as part of the license approval process and the lot release program.  If a product never contained thimerosal in the manufacturing process nor in the final product, CBER does not perform testing for the presence of thimerosal.

There are some products that use thimerosal as part of the manufacturing process, but the thimerosal is removed before the final stages of production and is only present in trace amounts.  As part of the licensing process, FDA requires manufacturers to validate all testing procedures as well as the entire manufacturing process.  FDA reviews and verifies acceptability of the submitted information during licensing, lot release and inspections.  If the product contains trace amounts of thimerosal due to residuals remaining at the end of the manufacturing process, CBER performs testing during the product licensing phase to verify that the manufacturing process to remove thimerosal consistently achieves values below the residual target level, and assesses the validity of the data submitted by the manufacturer's laboratory. CBER routinely reviews data generated by the manufacturer's testing laboratory on the lot release protocol.  CBER laboratories may also perform testing on samples in order to maintain assurance that the manufacturer's process continues to produce product below the allowed upper limit established.

I hope this information is helpful to you.

Sincerely,

Chris Middendorf
Chief
Consumer Affairs Branch
Division of Communication and Consumer Affairs Center for Biologics Evaluation and Research US Food and Drug Administration 301-827-2000 This communication is consistent with 21 CFR 10.85 (k) and constitutes an informal communication that represents my best judgment at this time but does not constitute an advisory opinion, does not necessarily represent the formal position of FDA, and does not bind or otherwise obligate or commit the agency to the views expressed.

-----------------------------

From: Twyla Ramos
Sent: Friday, February 15, 2008 11:25 PM
To: Middendorf, Christopher (CBER)
Subject: Re: trace amounts of thimerosal

Dear Mr. Middendorf,

Thank you so much for your email.  I'm wondering why this information was not available when I contacted the FDA three months ago?  I initially corresponded with Lanessa Hill (Public Affairs Specialist, Consumer Affairs Branch, Division of Communication and Consumer Affairs, Center for Biologics Evaluation and Research) and with Patricia H. Harley (Consumer Safety Officer, Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Communication, Training and Manufacturers Assistance, Division of Communication and Consumer Affairs).  Were they not authorized to give out this information?  They stated the basic procedures, but refused to tell me whether this testing included tests for mercury.  Is testing for mercury something new?  When did the FDA begin testing thimerosal content in vaccines which are supposed to contain only trace amounts?

You state that, in addition to testing as part of the license approval process, tests "may" be conducted later "to maintain assurance that the manufacturer's process continues to produce product below the allowed upper limit established".  Does this ever actually happen?  How rarely (or often) does testing of products occur after the license has already been approved?

Thank you so much.  I really appreciate your getting back to me.  It would put my mind at rest to know the answers to these additional questions.

Sincerely,

Twyla Ramos

parent

-----------------------------

From: Middendorf, Christopher (CBER)

To: Twyla Ramos

Cc: Middendorf, Christopher (CBER)

Sent: Tuesday, February 19, 2008 8:30 AM

Subject: RE: trace amounts of thimerosal

Dear Ms. Ramos,

Thank you for the follow-up questions.  I have to contact CBER's Office of Vaccine Research and Review (OVRR) for assistance in responding to your questions.  We have a Vaccines and Related Biological Product Advisory Committee meeting this week, so most of the people who will have the answers are out.  I will try to get something back to you early next week.

Thank you for your patience,

Chris Middendorf
Chief
Consumer Affairs Branch
Division of Communication and Consumer Affairs Center for Biologics Evaluation and Research US Food and Drug Administration 301-827-2000 This communication is consistent with 21 CFR 10.85 (k) and constitutes an informal communication that represents my best judgment at this time but does not constitute an advisory opinion, does not necessarily represent the formal position of FDA, and does not bind or otherwise obligate or commit the agency to the views expressed.

-----------------------------

From: Twyla Ramos [mailto:mramos1511@earthlink.net]
Sent: Tuesday, February 26, 2008 1:26 AM
To: Middendorf, Christopher (CBER)
Subject: Re: trace amounts of thimerosal

Dear Mr. Middendorf,

Hello.  I am just following up on my earlier email.  Have you had a chance to speak with your colleagues?  Thanks!

Twyla Ramos

-----------------------------

From: Middendorf, Christopher (CBER)

To: Twyla Ramos

Cc: Middendorf, Christopher (CBER)

Sent: Tuesday, February 26, 2008 4:57 AM

Subject: RE: trace amounts of thimerosal

Dear Ms. Ramos,

Yes, I have been in touch with our subject matter experts.  I'm trying to get clarification on a piece of information I was given.  Hopefully, I will have what I need today.

Again, thanks for your patience,

Sincerely,

Chris Middendorf
Chief
Consumer Affairs Branch
Division of Communication and Consumer Affairs Center for Biologics Evaluation and Research US Food and Drug Administration 301-827-2000

-----------------------------

From: Middendorf, Christopher (CBER)

To: Twyla Ramos

Cc: Middendorf, Christopher (CBER)

Sent: Thursday, February 28, 2008 11:39 AM

Subject: RE: trace amounts of thimerosal

Dear Ms. Ramos,

Not moving as quickly as I hoped, I'm trying to get the last bit of information to close this out.

Again, thanks for your patience,

Sincerely,

Chris Middendorf
Chief
Consumer Affairs Branch
Division of Communication and Consumer Affairs Center for Biologics Evaluation and Research US Food and Drug Administration 301-827-2000

-----------------------------

From: Twyla Ramos [mailto:mramos1511@earthlink.net]
Sent: Tuesday, February 26, 2008 11:01 AM
To: Middendorf, Christopher (CBER)
Subject: Re: trace amounts of thimerosal

Thanks again!

-----------------------------

From: Twyla Ramos [mailto:mramos1511@earthlink.net]
Sent: Monday, March 03, 2008 11:42 AM
To: Middendorf, Christopher (CBER)
Subject: Re: trace amounts of thimerosal

Still waiting...

-----------------------------

From: Middendorf, Christopher (CBER)

To: Twyla Ramos

Cc: Middendorf, Christopher (CBER)

Sent: Monday, March 03, 2008 9:08 AM

Subject: RE: trace amounts of thimerosal

Dear Ms. Ramos,

Thank you for your patience.  I have had request similar to yours, so I have attempted to put the information in a Q&A format.  There maybe some additional information that you did not request, however I believe this information answers your questions and clarifies previous responses.

How often does the FDA's conduct spot testing to evaluate thimerosal levels (quarterly, semi annually, etc) to verify independently that the manufacturer's testing results on the purification process?

Once confirmatory testing is completed during licensure, CBER does not routinely "spot check" products with "trace amounts" of thimerosal. A "spot check" may be initiated if there is a deviation from an approved manufacturing process and this deviation has the potential to lead to altered thimerosal levels, or through an assessment of other risk factors apparent during review of change Supplements, inspection, or routine data review. CBER routinely reviews thimerosal and/or mercury data generated by the manufacturer's testing laboratory as submitted on each lot release protocol. To ensure monitoring integrity, CBER does not publicize or otherwise inform manufacturers when testing occurs.

For products with more than "trace amounts", for example, products with thimerosal as a preservative, CBER reviews data generated by the manufacturer's testing laboratory in the lot release protocol. CBER laboratories may also perform testing on random samples in order to maintain assurance that the manufacturer's process continues to produce product below the allowed upper limit established. To ensure monitoring integrity, we don't routinely inform manufacturers in advance of testing which lots may be tested.

Are the results of FDA spot-testing in this regard available to the public?The public can obtain the results of confirmatory testing performed in support of BLA's and Supplements and any post licensure testing results through the Freedom of information Act
(http://www.fda.gov/opacom/backgrounders/foiahand.html#request)

Is testing for mercury something new?

No, testing for mercury has been taking place ever since its use as a preservative was advocated.

When did the FDA begin testing thimerosal content in vaccines which are supposed to contain only trace amounts?

Testing of vaccines for confirmation of removal or reduction of thimerosal levels begins concurrent with each submission of the supplement application to remove thimerosal or submission of a new product application. CBER performs testing during the application review phase to verify that the manufacturing process to remove thimerosal consistently achieves values below the residual target level, and assesses the validity of the data submitted by the manufacturer's laboratory.

Sincerely,

Chris Middendorf
Chief
Consumer Affairs Branch
Division of Communication and Consumer Affairs Center for Biologics Evaluation and Research US Food and Drug Administration 301-827-2000

-----------------------------

So, there you have it.  The FDA says that they perform testing during the product licensing phase, but, "Once confirmatory testing is completed during licensure, CBER does not routinely 'spot check' products with 'trace amounts ' of thimerosal. A 'spot check' may be initiated if there is a deviation from an approved manufacturing process and this deviation has the potential to lead to altered thimerosal levels, or through an assessment of other risk factors apparent during review of change Supplements, inspection, or routine data review."

Not sure why this information was too top secret or unknown to be released by the lower level FDA personnel back in November.

Today I sent one more email to Mr. Middendorf, asking a few additional questions.  Without congressional intervention, I don't know whether I will receive any answers.

-----------------------------

From: Twyla Ramos

To: Middendorf, Christopher (CBER)

Sent: Saturday, April 05, 2008 8:10 PM

Subject: Re: trace amounts of thimerosal

Dear Mr. Middendorf,

Thank you for this additional information about thimerosal content testing in vaccines.  From the timing of your initial email to me, I assume that your email was prompted by the January 17, 2008 letter to the FDA from Congressman Dan Burton, in which he spoke of an email exchange between "a parent" and the CDC and FDA.  (I am assuming that parent was me, although nobody has confirmed this.)  Representative Burton asked the FDA to respond to him by February 11, 2008, three days before your email to me.

I have been wondering about another question asked by Representative Burton, which is not addressed in your email:  "Has the FDA determined a safe reference dose for injected ethylmercury and thimerosal for adults and children?"  If so, how was such a determination made?  I have read the following information about mercury:

0.5 parts per billion (ppb) mercury = Kills human neuroblastoma cells (Parran et al., Toxicol Sci 2005; 86: 132-140).

2 ppb mercury = U.S. EPA limit for drinking water http://www.epa.gov/safewater/contaminants/index.html#mcls

20 ppb mercury = Neurite membrane structure destroyed (Leong et al., Neuroreport 2001; 12: 733-37).

200 ppb mercury = level in liquid the EPA classifies as hazardous waste.
http://www.epa.gov/epaoswer/hazwaste/mercury/regs.htm#hazwaste

How do we know that even "trace" amounts (defined as "less than 0.3 mcg") are safe?  I have read that the only testing of thimerosal was done in 1930 on a group of terminally ill people who died as expected, and on a group of dogs who became ill so thimerosal was declared unsuitable for use in dog vaccines.  Surely there must be some basis on which to decide that it is safe to inject trace amounts of mercury into a baby?

Also, why does the FDA continue to allow much more than a trace amount of mercury in flu shots, although flu shots can be made mercury-free simply by packing the shots individually, at only a slightly higher cost?  How on earth can these shots be o.k. for pregnant women, babies, and children?

In addition, in The Vaccine Book, Dr. Robert Sears says that he was unable to find any testing to confirm the safety of injecting aluminum into babies at the levels contained in many vaccines.  Could you please tell me how it was determined that aluminum in vaccines is safe?

Thank you in advance for addressing these concerns.

Sincerely,

Twyla Ramos

concerned parent