In the past three weeks, three state pharmacy associations have issued licensee communications on semaglutide compounding that misread (and misstate) FDA guidance on when 503a pharmacies can compound “essentially a copy” of an FDA-approved drug that is on the FDA drug shortage list.
The guidance states that if a drug is listed as “currently in shortage”—that’s the exact language—it may be compounded. The state boards I mentioned apparently went to the FDA website, saw that some dosage strengths of Wegovy or Ozempic were listed as “available,” and took that to mean they were not in shortage and thus could not be compounded.
But availability is not mentioned in the FDA guidance. “Currently in shortage” is the determinative language, and as of this writing, semaglutide remains in that category.
11/18/2022 – FDA Issues Guidance for Compounding of Amoxicillin to Alleviate Shortages Effective Immediately
Docket Number: FDA-2022-D-2922
Issued by: Center for Drug Evaluation and Research
This guidance describes the Food and Drug Administration’s (FDA or the Agency) regulatory and enforcement priorities regarding preparation of beta-lactam oral antibiotic suspension products that appear on FDA’s drug shortage list by a licensed pharmacist in a State-licensed pharmacy or Federal facility. There is currently an acute shortage of amoxicillin oral antibiotic powder for suspension. Amoxicillin oral antibiotic powder for suspension products currently appear on FDA’s drug shortage list. Amoxicillin is widely used for the treatment of bacterial upper and lower respiratory infections in the pediatric population, among other uses. As a result of this shortage, there is an urgent need to increase the supply of these beta-lactam oral suspension products. FDA has received a number of reports related to increased demand for amoxicillin oral antibiotic suspension products in particular. FDA has also received requests for clarification about preparation of compounded versions of those products from FDA-approved tablets and capsules.
9/30/2022 – FDA has declared desiccated thyroid extract (DTE) to be a biologic drug and therefore ineligible for compounding
The threat to compounded hormones just got real…
In a September 16 letter to National Association of Boards of Pharmacy CEO Al Carter, 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.”
The letter encourages NABP to share the letter with its members, the state boards of pharmacy, which Carter did in a memo to boards of pharmacy on September 22.
“This is a baffling move by FDA, both the substance of their categorization of DTE as a biologic and the back-door path they’ve taken in declaring it so,” said APC CEO Scott Brunner. “The letter to NABP comes not from FDA CDER leadership but from a branch chief in that division, and no public communication or announcement by FDA has yet been issued.”
“Can state boards of pharmacy be expected to use the letter to cite or otherwise restrict 503A compounding pharmacies that compound with DTE?” Brunner asked.
“We are concerned that states may do just that, but at this time, with so little information, we do not know the approach boards may take on DTE, especially given the significant patient access issues to this important medication that such state action will create.”
“FDA says in the letter that it considers thyroid USP to be a biologic on the basis of a component in the product, thyroglobulin, that is not even an active ingredient of the medication,” said APC President Dave Miller. “Yet neither thyroid USP nor thyroglobulin are listed in FDA’s Purple Book. In addition, the commercially available thyroid USP drug products make no mention of thyroglobulin on their products’ inserts or labeling. If thyroglobulin may cause the patient harm FDA says it does, why is it not even mentioned on those inserts or labels?”
Brunner has reached out to FDA OCQC Director Gail Bormel to request an immediate meeting about the letter and apparent reclassification.
“If you’ve been looking for evidence that FDA aims to restrict hormone compounding, you have to view this as the first real shot fired,” said Brunner. “Now it’s all the more important that we get the funding we need to engage patients and members of Congress—and likely lawyers, too—to push back against this overreach by the agency.”
Want to help? Start by taking the A4PC four-question survey
You may also want to share the briefing document with your state board of pharmacy, so they’ll be aware of our concerns about patient access.
In addition, A4PC has created a very brief survey aimed at helping us quantify the effects of thyroid USP compounding. Please complete the survey at your first opportunity:
“After we know more from FDA about this action they’ve taken, APC will likely issue a call to action to our members and patients urging them to reach out to Congress and FDA,” said Miller. “Stay tuned, and be ready to respond.”
5/18/2022 – Meeting of the Pharmacy Compounding Advisory Committee Meeting Scheduled for June 8, 2022
The meeting presentations will be heard, viewed, captioned, and recorded through an online teleconferencing platform. The committee will discuss the following four bulk drug substances nominated for inclusion on the 503A Bulks List: Ammonium tetrathiomolybdate, enclomiphene citrate, ferric subsulfate, and glutathione. The chart below identifies the use(s) FDA reviewed for each of the four bulk drug substances being discussed at this advisory committee meeting. The nominators of these substances or another interested party will be invited to make a short presentation supporting the nomination.
|Bulk Drug Substance||Uses Evaluated|
|Ammonium Tetrathiomolybdate||Wilson disease, use as copper (Cu) chelation therapy for the treatment of breast cancer, kidney cancer, prostate cancer, colorectal cancer, esophageal cancer, and malignant pleural mesothelioma.|
|Enclomiphene Citrate||To increase serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) to normal levels in the treatment of secondary hypogonadism.|
|Ferric Subsulfate||For use as an astringent and hemostatic agent during minor
|Glutathione||Skin lightening, cystic fibrosis, asthma, chronic obstructive pulmonary disease, chronic lung disease, oxidative stress, reduction of the side effects of chemotherapy, inhibition of chemical induced carcinogenesis, prevention of radiation injury, treatment of heavy metal poisoning (cadmium and mercury), acetaminophen toxicity, autism spectrum disorder, Alzheimer’s disease, Parkinson’s disease, major depressive disorder, schizophrenia, helicobacter pylori infection, human immunodeficiency virus infection, tuberculosis, otitis media, peripheral obstructive arterial disease, anemia, diabetes, and septic shock.|
The committee will also discuss revisions FDA is considering to the Withdrawn or Removed List. FDA now is considering whether to amend the rule to add one more entry to the list: Lorcaserin Hydrochloride: All drug products containing lorcaserin hydrochloride. As previously explained in the Federal Register of July 2, 2014 (79 FR 37687 at 37689 through 37690), the list may specify that a drug may not be compounded in any form, or, alternatively, may expressly exclude a particular formulation, indication, dosage form, or route of administration from an entry on the list. Moreover, a drug may be listed only with regard to certain formulations, indications, routes of administration, or dosage forms because it has been found to be unsafe or not effective in those particular formulations, indications, routes of administration, or dosage forms. FDA plans to seek the committee’s advice concerning the inclusion of this drug on the list.
FDA intends to make background material available to the public no later than two (2) business days before the meeting. If FDA is unable to post the background material on its website prior to the meeting, the background material will be made publicly available on FDA’s website at the time of the advisory committee meeting. Background material and the link to the live webcast will be available at 2022 Meeting Materials, Pharmacy Compounding Advisory Committee. Scroll down to the appropriate advisory committee meeting link. The meeting will include slide presentations with audio components to allow the presentation of materials in a manner that most closely resembles an in-person advisory committee meeting.
Public Participation Information
Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee.
FDA is establishing a docket for public comment on this meeting. The docket number is FDA-2021-N-0357. The docket will close on June 7, 2022. Submit either electronic or written comments on this public meeting by June 7, 2022. Please note that late, untimely filed comments will not be considered. Electronic comments must be submitted on or before June 7, 2022. The https://www.regulations.gov electronic filing system will accept comments until 11:59 p.m. Eastern Time at the end of June 7, 2022. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are postmarked or the delivery service acceptance receipt is on or before that date.
Comments received on or before May 24, 2022, will be provided to the committee. Comments received after that date but by June 7, 2022 will be taken into consideration by FDA. In the event that the meeting is cancelled, FDA will continue to evaluate any relevant applications or information, and consider any comments … READ MORE
Today, the U.S. Food and Drug Administration issued a final guidance, entitled “Compounding Animal Drugs from Bulk Drug Substances,” that will help protect animal health by recognizing the need for access to certain compounded animal drugs. The guidance describes the agency’s approach to situations where veterinarians use unapproved compounded drugs to provide appropriate care for the medical needs of the diverse species they treat. The FDA recognizes that this final guidance covers a wide range of stakeholders and plans to focus on education and stakeholder engagement before shifting resources toward inspectional activities in Fiscal Year 2023. We will take appropriate actions, as we currently do, when compounding practices threaten human or animal health.
Animal drug compounding is the process of combining, mixing or altering ingredients to create a medication tailored to the needs of an individual animal or a small group of animals. Animal drug compounding using an FDA-approved drug as the starting point is already allowed under existing law and regulations. Animal drugs compounded from bulk drug substances are not FDA-approved and the agency has not evaluated them to ensure that they are safe, effective, properly manufactured to ensure consistent quality, and the labeling is complete and accurate.
“We are taking this step because we recognize the need for veterinarians to have access to compounded animal drugs that aren’t available as approved products and that would make a clinical difference in patient care,” said Steven M. Solomon, D.V.M., M.P.H., director of the FDA’s Center for Veterinary Medicine. “We believe this policy strikes the right balance between maintaining access to drugs veterinarians need to treat diverse animal populations, while ensuring human and animal health is protected from poorly-compounded products, or ones that attempt to copy existing FDA-approved drugs.”
There are more than 1,600 drugs that are FDA-approved, conditionally approved or indexed for use in animals, as well as approximately another 20,000 FDA-approved human drugs that could be prescribed for animal use. At the same time, there are many different species of animals, each with various diseases and conditions for which no suitable FDA-approved or indexed drugs are available… READ MORE
ALEXANDRIA, Va. — In a significant legal victory for pharmacy compounders, the U.S. Food & Drug Administration has conceded that it must conduct formal notice-and-comment rulemaking to implement its memorandum of understanding with states regarding interstate shipments of compounded medications. The agency concession is related to a lawsuit, Wellness Pharmacy v. Azar, brought in federal court against the agency in 2020 by seven compounding pharmacies. The Alliance for Pharmacy Compounding was party to an amicus filing in the case.
In a status report filed yesterday with the U.S. District Court for D.C., FDA said it would suspend implementation of the MOU and engage in a formal rulemaking process. The agency indicated in its filing that the process may take “several years” to complete.
FDA’s concession follows a ruling by federal judge Chris Cooper last autumn that FDA had failed to meet the requirements of the Regulatory Flexibility Act in promulgating the MOU. The judge had ordered the agency to report back to the court its plans for addressing the matter.
“We’re pleased that compounders’ concerns and arguments have prevailed in this case,” said APC President Dave Miller, managing owner of Keystone Pharmacy in Grand Rapids, Mich. “While this litigation resulted from what we view as FDA overreach, we do support the agency’s desire for reporting by compounded pharmacies that ship the majority of the medications they compound to patients in other states. Now, with this case settled, we’re committed to work with FDA and Congress to enact an effective reporting framework that meets FDA’s need for information and doesn’t threaten patients’ access to compounded medications. And I would add: We think there are ways to bring about that result that won’t take years and years to effect.”
The MOU in question was mandated by Congress a quarter century ago, in a 1997 update of the Food, Drug & Cosmetic Act. In the intervening years, three draft versions of the MOU were issued and rescinded by FDA based on stakeholder feedback. It was finalized by the agency in 2020, with an October 2021 deadline for states to sign it. In signing the MOU, states would agree to share with FDA information on compounding pharmacies based in the state that ship more than 50 percent of compounded medications out of state. In states that fail to sign the MOU, the statute would allow a compounding pharmacy to ship ... READ MORE
2/16/2022 – FDA alerts health care professionals of potential risks associated with compounded ketamine nasal spray
FDA has become aware of safety reports involving compounded intranasal ketamine to treat psychiatric disorders which may be putting patients at risk. Compounded drugs are not FDA-approved, which means FDA has not evaluated their safety, effectiveness, or quality prior to marketing.
Ketamine hydrochloride[a] (tradename: Ketalar) is a Schedule III controlled substance that is FDA-approved as an intravenous or intramuscular injection solution for induction and maintenance of general anesthesia. Ketamine is a racemic mixture consisting of two mirror image molecules, R- and S-ketamine. FDA-approved labeling for ketamine contains warnings and precautions on hemodynamic instability, emergence reactions (vivid dreams, hallucinations, or delirium), respiratory depression, and drug-induced liver injury, among others.
Ketamine is not FDA-approved for the treatment of any psychiatric disorder. However, the “S” form of ketamine, which is derived from ketamine and known as Spravato (esketamine), is a Schedule III controlled substance that was approved by FDA in 2019 as a nasal spray for treatment-resistant depression in adults and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior, in conjunction with an oral antidepressant. Because of the potential risks associated with Spravato (esketamine), including sedation, dissociation, and abuse or misuse, its label contains Boxed Warnings, and Spravato is subject to strict safety controls on dispensing and administration under a safety program called a Risk Evaluation and Mitigation Strategy (REMS). The Spravato REMSprogram requires Spravato (esketamine) to be dispensed and administered in health care settings that are certified in the REMS. Spravato (esketamine) cannot be dispensed for use outside the certified healthcare setting. Patients must be monitored inside the healthcare setting after administration for a minimum of two hours until patients are safe to leave.
Though esketamine is derived from racemic ketamine, they are not the same drug. Animal studies have shown that racemic ketamine can cause lesions in the brains of rodents; the relevance of this finding to humans is unknown. Animal studies with esketamine do not… READ MORE
FDA is working to provide guidance to states and compounders on issues associated with compounding drugs during the COVID-19 pandemic. The agency’s guidance aims to protect patients from unsafe, ineffective and poor-quality compounded drugs, while preserving access for patients.
Outsourcing Facility Product Reports for Hospitalized Patients with COVID-19:
The agency issued a guidance for temporary compounding of certain drugs by outsourcing facilities during the COVID-19 public health emergency. Hospitals that cannot obtain FDA-approved drugs covered by the guidance and seek to use compounded drugs for their patients should first contact outsourcing facilities, which produce compounded drugs under more robust quality standards than those made by state-licensed pharmacies or federal facilities not registered as outsourcing facilities. Hospitals can use the product report to help determine which outsourcing facilities are compounding drugs used for hospitalized patients with COVID-19.
• The agency’s draft hospital and health systems guidance, which includes the “one mile radius” provision, is still in draft and we are planning to issue a revision. This draft guidance was issued for public comment and has not been implemented.
• Although federal law specifies a 5 percent limit on distribution out of state of drugs compounded by pharmacies and physicians regulated under section 503A of the Federal Food, Drug and Cosmetic Act, the agency does not intend to enforce the 5 percent limit until after the agency has finalized a Memorandum of Understanding (MOU) and given states an opportunity to sign it.
• The agency does not consider drugs that are on FDA’s shortage list or that have been discontinued and are no longer marketed to be “commercially available” under the “essentially a copy” provision for pharmacy and physician compounders... READ MORE
10/6/2021 – FDA Revises Hospital and Health System Compounding Guidance to Help Preserve Patient Access to Compounded Drugs
Compounded drugs can serve an important role for patients whose medical needs cannot be met by an FDA-approved drug. The FDA is continuing our efforts to help preserve access to compounded drugs for patients who have a medical need for them.
We understand that compounded drugs can serve an important role for patients in hospitals and other healthcare settings whose medical needs cannot be met by an FDA-approved product, and that hospital care raises unique considerations and needs. Recognizing this, in 2016 the agency proposed a policy in draft guidance, that described certain flexibilities for hospital and health system pharmacies that distribute compounded drugs within their health system before receiving patient-specific prescriptions.
Since that time, the agency has received many comments on this proposed policy, including regarding a provision about FDA’s intent not to take action if a hospital or health system pharmacy distributes compounded drugs to healthcare facilities within a one-mile radius, that are owned and controlled by the same entity that owns and controls the pharmacy. Stakeholders commented that the proposed one-mile policy was not reflective of the structure of health systems, many of which operate under a centralized compounding model and may service facilities at other sites located outside a one-mile radius without similar compounding capabilities.
After considering these comments, to help preserve access to compounded drugs, today, the FDA is revising our draft guidance to, among other things, remove the one-mile radius provision. We are proposing a two-part compliance policy. The policy describes circumstances under which the agency generally does not intend to take action against a hospital or health system pharmacy, that is not an outsourcing facility, that compounds and distributes a drug without first receiving a valid prescription or order for an individual patient. These circumstances include that compounded drugs be administered only to patients within the hospital or health system and the drugs are used or discarded within 24 hours of leaving the pharmacy.
With respect to hospital and health system pharmacies that deviate from these circumstances, the revised draft guidance outlines the FDA’s intention to take a risk-based approach to enforcement. Hospital and health system pharmacies can measure their operations against certain factors to assess whether their practices are likely to be an enforcement priority. At this time and based on the agency’s current understanding of the risks, the FDA generally intends to consider the following factors… READ MORE
7/2/2019 – NASEM Study on the Clinical Utility of Treating Patients with Compounded “Bioidentical” Hormone Therapy
NASEM provided FDA with its analysis of compounded bioidentical hormone therapy (cBHT), such as estradiol, estrone, dehydroepiandrosterone and testosterone, on July 1, 2020. They are often advertised as having certain advantages over FDA-approved products, such as being derived from natural sources, being effective and safer than FDA-approved drugs that are synthetic or chemically modified, or not having the risks or side-effects associated with FDA-approved hormone therapies.
Based on its research and analysis, NASEM determined there was a lack of rigorous evidence of safety and effectiveness from well-designed or properly controlled clinical studies. NASEM found information about the safety and effectiveness of cBHT came mostly from low quality data, such as anecdotal claims, patient reports, and prescriber testimonies. Further, there is limited federal and state-level oversight of the quality and use of cBHT preparations. Given the lack of high-quality clinical evidence and minimal oversight of cBHT, NASEM concluded that their wide-spread use poses a public… READ MORE