Is Desiccated Thyroid Extract (DTE) a Biological Drug Ineligible for Compounding?
As alluded in a recent declaration that desiccated thyroid extract (DTE) is considered a biologic, FDA may be in the beginning stages of banning compounded drugs containing desiccated thyroid extract. Compounding pharmacies believe the announcement is a direct threat to the future of compounded thyroid drugs. What remains to be seen is how quickly (or if ever) the federal agency will move to enforce this position.
FDA Issues Letter to Pharmacy Board Addressing "Harmful" DTE
In a September 16 letter addressed to Lemrey "Al" Carter, Executive Director/Secretary of the National Association of Boards of Pharmacy (NABP), the Food and Drug Administration (FDA) declared they have "become aware of desiccated thyroid extract (DTE) that appears to have been prepared by state-licensed pharmacies being offered to patients."
The FDA states that DTE products "can put patients at harm" and that "therapies containing DTE are biological products subject to licensure under Section 351(i) of the PHS Act."
Al Carter issued a letter to the NABP and asked for the letter from the FDA to be shared with member boards and others across America.
After the initial letter from the FDA was distributed, some suppliers of DTE stopped selling the active pharmaceutical ingredient (API) to pharmacies. This was not the only disturbance in the industry after the announcement, some pharmacies were told by board inspectors they could no longer compound DTE to meet the needs of their patients.
Feedback from Alliance for Pharmacy Compounding (APC) representatives who attended follow up meetings with the FDA after their September letter claims the agency is inconsistent about which substances it has reclassified and which products the reclassification affects.
FDA's September Declaration Letter
The images below are a copy of the letter sent from the FDA to the State Boards of Pharmacy CEO, Mr. Al Carter, and has been made public by Al Carter.
After receiving the FDA’s letter, APC created a preliminary briefing document addressing the issue. It outlines primary concerns from compounding pharmacies and boards. Read the letter here.
Compounding Pharmacies Are Concerned
The FDA's declaration that natural desiccated thyroid (NDT) is now considered a biologic could make it ineligible for pharmacy compounding. 503A compounding pharmacies are worried that state boards of pharmacy might use the letter to cite or otherwise restrict compounding pharmacies that compound with DTE. Many believe that this latest announcement is a decades-long effort by the agency to remove natural thyroid medications from the market in favor of FDA-approved thyroid drugs, which many patients cannot use. If this is true, it could threaten access for millions of patients who need NDT to stay healthy.
Is Thyroglobulin an Inactive Ingredient or a Biologic?
According to the FDA in a FAQ posted online, a biological product, according to Section 351 of the Public Health Service (PHS) Act, defines a biological product as, “a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, … applicable to the prevention, treatment, or cure of a disease or condition of human beings.” FDA regulations and policies have established that biological products include blood-derived products, vaccines, in vivo diagnostic allergenic products, immunoglobulin products, products containing cells or microorganisms, and most protein products. Biological products subject to the PHS Act also meet the definition of drugs under the Federal Food, Drug and Cosmetic Act (FDC Act).”
In the September letter, the FDA said that it considers thyroid USP to be a biologic based on a component in the product, thyroglobulin, that is not an active ingredient of the medication. The agency based their judgement on the amount of amino acids in thyroglobulin --- under the definition of a protein --- under the definition of a biologic.
Thyroglobulin is not listed in the FDA’s Purple Book. The Purple Book is a list of licensed biological products, which was once two separate lists but has transitioned to a searchable online database.
David Pore and Scott Brunner of APC voiced several concerns over the FDA’s declaration in a September 2022 letter, from the Alliance for Pharmacy Compounding (APC).
One of their bullet points states, “In addition to thyroglobulin not being the active ingredient, Section 503A of the FDCA allows for chemicals to be used as the API of a human drug compound if the chemical has an applicable USP monograph. FDA has indicated that applicable USP monographs are the “drug” monographs in USP. Thyroid USP has an applicable drug monograph, and thyroglobulin content is not a specification to be tested for in the monograph. Compounding pharmacies combine an active pharmaceutical ingredient (API) – in this case, natural desiccated thyroid powder – with other ingredients into a capsule form.”
FDA’s Indirect Approach
The FDA claims that NDT meets the definition of a biologic since it contains thyroglobulin, an amino acid found in the pig glands used to make NDT. Biologics cannot be compounded unless there is an approved biological license application (BLA), akin to a new drug application requiring clinical trials and extensive capital.
Compounding pharmacy groups are pushing back, calling this a “back door” method. They believe FDA has been attacking this kind of natural medicine for years. Because of the highly varied and individualized doses and delivery mechanisms prepared in compounded medicines, clinical trials would not be able to be conducted, thus new drug approvals never realized.
What is the FDA’s Policy Goal?
According to FDA’s Office of Quality and Compliance (OCQC) Director Gail Bormel, the reclassification was “always” going to happen because of the Biologics Price Competition and Innovation Act of 2009 (BPCI Act) which was passed by Congress in 2010, with enforcement that began in March 2020.
Representatives of pharmacies, especially APC leaders state that Thyroid USP wasn’t listed in the official notices and that thyroglobulin isn’t an active ingredient in Thyroid USP. Thyroid USP is the name of the API used in many brands of natural thyroid medications such as Armour Thyroid and NP Thyroid.
“The agency seems to be focused on thyroglobulin based on research related to some old products that had listed it as an active ingredient, but which were taken off the market years ago. So, they’re jumping to DTE, which contains thyroglobulin as a by-product, and they’re making no distinction that it’s not the active ingredient.” said APC President Dave Miller.
Compounders vs. Big Pharma
Compounded natural thyroid drugs compete with FDA-approved T4 thyroid drugs (e.g., levothyroxine, Synthroid, etc.). Levothyroxine’s market size is $2.3 billion, which is expected to grow to $3.5 billion by 2027. In a list of the top 300 most prescribed drugs of 2020, levothyroxine was listed as number two, with over 20 million patients and just under 99 million prescriptions. For many years, Synthroid was the top prescribed medicine in the US. Compounded natural thyroid, and the pharmacies that produce it, therefore, represent an annoyance to Big Pharma.
The FDA declares that NDT medicines, which do not go through FDA approval, cannot be guaranteed safe or effective, nor can hormone levels be guaranteed from batch to batch. However, compounding pharmacies point out that natural thyroid has been compounded for years safely, without issues.
APC’s Update on the FDA’s September Letter
After FDA submitted the letter in September, they met with APC representatives in October 2022. Shortly after in November, FDA issued two additional letters to clarify their initial declaration regarding DTE. In the November 16 letters, FDA stated that DTE products would continue to be available, and they intend to make additional information open to the public. The FDA noted they would address complaints related to DTE products prepared by state-licensed pharmacists. To date, they have yet to take steps to remove products prepared by drug compounders or limit compounder access to DTE.
In an update letter that addressed the FDA’s November letters, Scott Brunner, CAE of APC said, “Based on our conversations with FDA officials, we interpret those statements to mean that FDA intends, at least for the foreseeable future, to take no action against compounders of DTE unless they receive a complaint about adverse events or product quality—in which case, the agency would commence an investigation of the pharmacy that prepared the DTE drug that is the source of the complaint.”
What To Do and What’s Next?
The APC has been heavily involved with this matter, and held an October 13th town hall meeting for their members. Since then, the APC met with members of the FDA in an online meeting in November which helped clarify some questions, however many questions still go unanswered.
FDA is currently asking people who are concerned or wish to provide information to email them at compounding@fda.hhs.gov.
APC is asking concerned pharmacists and community members to reach out to state’s Board of Pharmacy members and director and urge them to attend to the memos. Representatives of APC will speak to the Board about these issues if invited. Should you want to share any feedback with the APC please email them at info@a4pc.org. You can also reach out to APC members David Pore at dpore@hslawmail.com or Scott Brunner at scott@a4pc.org.
WHERE DOES YOUR FACILITY STAND?
If you’re looking to become compliant with the new USP 797 and USP 795 requirements or if you wonder how you measure up against the desiccated thyroid topic, let consultants at Restore Health Consulting LLC perform a gap analysis to assess your pharmacy or hospital compliance status against the new minimum standards and lead remediation planning if needed.
Resources
FDA Letter Regarding Desiccated Thyroid Extract Preparations
FDA uses back door to restrict DTE compounding
Frequently Asked Questions About Therapeutic Biological Products
Here’s how to help preserve access to desiccated thyroid extract
ISSUE BRIEF: FDA restricts thyroid compounding options
The threat to compounded hormones just got real
(APC Scott Brenner Letter) Update on compounded desiccated thyroid extract (DTE)
What’s Happening With Natural Desiccated Thyroid Drugs?
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