Gluten Levels in Medication: FOIA Request

Update: Six years after filing this FOIA, FDA finally responded:

This is in response to your electronic Freedom of Information Act request dated in which you requested information regarding NFCA grant 4288. Specifically, your request seeks “GFW seeks all data reflecting testing for gluten content from the FDA-sponsored study Gluten in Medication… A search of the records of the Center for Drug Evaluation and Research did not locate responsive records. Specifically, Division of Information Disclosure Policy has confirmed that FDA received only the final study report and did not receive the underlying data. Therefore, we have no documents to provide you.”

FDA is charging Gluten Free Watchdog $23 for the search.

……….

It has been three years since I filed a Freedom of Information Act (FOIA) request with the FDA asking for testing data from an FDA funded study on the gluten levels in medications. FDA has yet to process my request.

Bottom line: FDA has concluded that medications are unlikely to contain more than 0.5 mg of gluten per unit dose (see Gluten in Drug Products Proposed Guidance available at https://www.glutenfreewatchdog.org/news/gluten-in-drug-products-proposed-guidance-please-comment/). This conclusion may in fact be accurate BUT it is based at least in part on testing data that may be flawed.

Why we are concerned about the testing data

At issue is the apparent belief of the authors of the FDA funded study that the part per million gluten level changes based on medication dosage. Part per million is a proportion/percentage. One pill, 1/2 pill, or the entire bottle has the same ppm value. What changes based on dosage and ppm gluten level is the milligram amount of gluten ingested.

The study authors’ apparent confusion regarding ppm is illustrated in the following passage from the study:

“Testing Methods: Four drugs (esomeprazole capsules, tramadol tablets, diphenhydramine HCL tablets and chlorthalidone tablets) tested positive in the Competitive ELISA when their gluten concentrations were examined in raw form. Since the Competitive assay protocol required taking 1000 mg of sample, we had to use 4.58 tablets for esomeprazole, 4 tablets for tramadol, 3.88 tablets for diphenhydramine and 7.09 tablets for chlorthalidone for the assay. Adjusting the assay result for a subsample of 1 tablet/capsule resulted in the ppm for these drugs to be below 10ppm, the level of quantification. For this reason, we are reporting that these drugs tested below the LOQ, and therefore negative for gluten.”

Why the FOIA request was filed: In the interest of transparency, we are asking the FDA to release what the authors of the FDA commissioned study term “raw “ ppm test results for all drugs tested. This would be the ppm gluten result before the researchers appear to have erroneously recalculated the ppm amount based on dosage size.

What you can do:

1. Familiarize yourself with the issue by reading the timeline and FOIA request posted below.
2. Know that we are considering next steps to help speed up the release of the “raw” ppm values.
3. Know that medication may contain little gluten even when the ppm level is at/above 20.
   1. This is because the weight amount of most medication dosages is low.
   2. As a result the amount of gluten ingested is low.
      1. For example if a medication contains 20 ppm of gluten, you would have to ingest one ounce of medication (this is a lot) to take in about ½ milligram of gluten.
   3. Regardless, we need the testing data to know the true level of risk.
4. Contact us if you work at a hospital or pharmacy and can help arrange to have expired medication sent to the lab used by Gluten Free Watchdog.
   1. Without a license, it is illegal to send prescription medication through the mail.

Timeline of communication with FDA

• July 23, 2015: FOIA request faxed to FDA.
• January 11, 2016: Emailed FDA as I had not received confirmation that my FOIA had been received.
• February 18, 2016: Resent FOIA request via email to FDA.
• February 23, 2016: Received confirmation from FDA that my FOIA request was received.
• April 2017: Contacted FDA by phone requesting an update on my FOIA request.
• April 26, 2017: FDA responded via email to my request stating that, “Regarding your telephone inquiry as to the processing status of your Freedom of Information Act request designated REDACTED, please be advised that The FDA CDER processes FOI requests in a two track system. That system operates on a first in first out basis. Your request has been assigned to the complex queue. Cases assigned to the complex queue generally experience a processing time frame of approximately 18 to 24 months. Your request is in the queue, and will be processed in turn.”
• April 27, 2018: Emailed FDA again for a status report.
• April 27, 2018: FDA replied stating, “Regarding your inquiry as to the processing status of your Freedom of Information Act request designated REDACTED, please be advised that your request is now approximately number 177 in the queue. Your will be processed in turn.”
• December 3, 2018: Emailed FDA again for a status report.
• December 4, 2018. FDA replied stating, “Regarding your inquiry as to the processing status of your Freedom of Information Act request designated REDACTED, please be advised that your request is now approximately number 130 in the queue. Your request will be processed in turn.”
• December 4, 2018: I replied stating, “Thank you for the update. As a reminder, I filed this FOIA in February 2016, close to 3 years ago. In April 2018 my request was 177 in the complex queue. Eight months later it is 130 in the queue. At this rate (moving up 6 spots per month), it will be approximately 2 years before my FOIA request is processed. Five years to act on a FOIA request, especially when the request pertains to a proposed FDA rule/guidance, seems somewhat protracted. Is it possible to speed up the process so that I can receive the data requested?”
• December 4, 2018: FDA replied stating, “As a result of the high volume of requests ahead of your request and the complexities and restraints on processing in general, there is no recommendation that I can make to you in order to speed up the processing or your request.”

FOIA request (pasted in full as submitted to FDA)

FOIA Request Pertaining to Federal Document ID FDA-2008-P-0333-0030

Contact Information:

Name: Tricia Thompson, MS, RD

Address: REDACTED

Phone: REDACTED

Data Requested:

Data from study cited in Federal Document ID FDA-2008-P-0333-0030 (Citizen Petition Partial Approval and Denial Response Letter from FDA CDER to Mr. Michael Weber). NOTE: There is no actual citation provide for this study but it is publicly available at http://www.celiaccentral.org/SiteData/docs/PublicRepo/9180ed94e35ad91f/Public%20Report_revised_5_2015.pdf

Note: The requested data is not included in the public report. This report is simply a summary of the data.

39

FDA funded a study recently completed by the National Foundation for Celiac Awareness (NFCA) in which 39 drugs were tested for gluten. See the NFCA’s study report, “Gluten in Medication: Qualifying the extent of exposure to people with celiac disease and identifying a hidden and preventable cause of an adverse drug event” (September 14, 2014) (currently available on the NFCA’s Web site. www.celiaccentral.org). Of the 39 drugs tested, the NFCA reported that 3 drugs tested positive for gluten in one test and none tested positive for gluten in another test. Without commenting in detail on the NFCA study, we note that the highest result the NFCA reported, 0.077 mg gluten in a unit dose, is consistent with the analysis we present in this letter and is a small fraction of the amount of gluten that may be present in a single cookie properly labeled gluten-free (e.g., up to 0.6 mg gluten in a 30-gram serving of food). We recognize that there are challenges associated with analytical testing of finished drug products for gluten and would welcome additional research in this area.

Specific Request:

Specifically, I am requesting all available gluten testing data from the FDA funded study completed by NFCA, including the parts per million gluten levels found in the 39 drugs tested for gluten. This data should include the initial raw data from product testing as well as the author-computed parts per million values for medication by dosage amount. The calculations used to arrive at these values would also be helpful.

Willingness to Pay Fees:

I am willing to pay reasonable fees for this data. However, this request is being made because the data included in the study is likely flawed. As stated to the author (Janet Woodcock) of the FDA response letter:

The cited study has some potential flaws that I and others discussed at length with the lead authors after the study was first posted on the NFCA website in 2014. It was revised in May 2015. The May version is currently posted on NFCA’s website. At issue is the belief of the authors that the part per million gluten contamination value changes based on medication dosage. As you know, ppm is a proportion/percentage. It does not change. Assuming the ppm values are accurate one pill, 1/2 pill, or the entire bottle has the same ppm value. What obviously changes based on dosage and ppm contamination level is the milligram amount of gluten ingested.

Thank you,

Tricia Thompson, MS, RD

Owner/Founder Gluten Free Watchdog, LLC

Note to the Gluten Free Watchdog community, NFCA (now Beyond Celiac) was awarded a study grant from FDA but they did NOT conduct the study. Beyond Celiac assembled a team of researchers who conducted the study and developed the report. The study authors were made aware of my concerns.