Progress and an Opportunity
As many of you know, this past September, 25 bipartisan members of Congress sent a letter to the FDA questioning their actions on homeopathic medicines. If you missed that, here is a copy of that letter. Interestingly, FDA recently sent a response, and it continues on the overall trajectory of concern. The FDA’s letter revealed that the Agency still has many misunderstandings regarding homeopathic medicines. We believe that–in part–these misunderstandings are due to the Agency not having a homeopathic subject matter expert involved as they make policy decisions around homeopathic medicine. Our role is to help the FDA so that its actions include the consumer voice and support continued consumer access to quality homeopathic medicines. FDA’s response letter to Congress posed a very strong opportunity to present to Congress the facts about homeopathic medicines and our concerns with the FDA’s new direction. With that in mind, below is our response to the FDA’s letter.
Background
Americans for Homeopathy Choice (AFHC) is an advocacy group that was formed to foster inclusion of the consumer voice in policy decisions on homeopathic medicine—a complete system of medicine used by nearly 250,000 physicians and over 500 million people worldwide. [1] The medicines are formulated using commonly available and unpatentable substances such as onion, aloe, elderberry, black tea, and coffee. Considering the benefits of homeopathic medicines when used based on an individual’s unique collection of symptoms, [2] the Food, Drug, and Cosmetic Act (FD&C Act) included the Homeopathic Pharmacopoeia of the United States (HPUS) and its supplements in the Act to give the FDA the tools to regulate homeopathic medicines as a unique and separate category of drugs to ensure both consumer access and safety. [3]
Our members, who are mostly parents and other consumers, are concerned about the FDA’s recent substantial policy change regarding homeopathic medicines in its 2017 draft guidance (slightly revised in 2019)—a change that has begun to harm the American economy and our access to health care options that work for us.
Twenty-five bipartisan members of Congress recently wrote a letter to the FDA inquiring how the FDA intends to utilize and adhere to the legal framework that protects consumers and ensures access to quality homeopathic medicines. FDA Acting Associate Commissioner for Legislative Affairs, Mr. Andrew Tantillo, responded to the inquiry in November 2021. We greatly appreciate the FDA’s attention to this issue. However, the response left a number of issues unresolved that we seek to address—most importantly, the response does not answer how homeopathic medicines will remain available to the growing number of Americans who consider them an essential component of health care.
American Small Businesses and the Health of Americans at Stake
As an illustration of our concerns with the FDA’s draft guidance, there is an American small business which manufactures homeopathic medicines in the US and also imported some of their products from Europe. The FDA, citing the guidance, blocked the importation of the company’s homeopathic medicines without any evidence of harm or failure to meet standards (hereinafter referred to as “Import Case”). The products, which are administered only by physicians for relief of pain and other symptoms, have been used 325 million times over the last 20 years without a single report of death and only one report of an adverse drug reaction (ADR). [4] Compare that to more than 86,000 ADRs and more than 14,000 deaths from corticosteroids, which are used for pain relief, in the last 18 years. [5] The company has been in business for over 40 years, has passed every FDA inspection, and now has spent almost $1 million challenging the FDA’s action and paying severance to employees. Sadly, Americans who relied on the company’s products for years, even decades, no longer have access to them. It’s important to note that these homeopathic medicines helped many avoid opioids for chronic pain conditions. While the FDA states, without any formal process, that its actions are within the ambit of its enforcement discretion, the direct result punishes compliant homeopathic manufacturers and reduces consumer access in such a way that is inconsistent with the intent of the FD&C Act and its application to homeopathic medicines.
Regulation-by-Guidance and a Pending Citizen Petition
The Import Case is a devastating example of how manufacturers, practitioners, and most importantly, the health of individuals, are being directly impacted by decisions made outside of the rulemaking process. Mr. Tantillo’s letter makes abundantly clear that the FDA intends to move forward with a substantial change to the regulation of homeopathic medicines using a “guidance.” [6] We believe that the application of pharmaceutical-specific premarket approval (referencing the 1962 Kefauver-Harris Amendments) to homeopathic medicines is actually a change in the “legal norm” by the FDA. [7] For the past 83 years, the FDA has supported the intent of Congress by not applying premarket approval to homeopathic medicines (see further discussion below). Regulating by guidance is a practice of which members of Congress, as well as the courts, have been increasingly critical. An agency must not circumvent its rulemaking obligation to the public under the Administrative Procedure Act (APA) through guidance—a change in policy that has generated over 115,000 public comments in total. [8]
In addition, Mr. Tantillo’s letter fails to report that AFHC has a pending Citizen Petition, dated June 5, 2020, in accordance with the APA which addresses in detail each of the issues he raised. [9] AFHC has earnestly sought to resolve these issues by working with the FDA including multiple meetings with senior Agency officials. However, we have been limited by the ambiguous guidance process and the lack of response to numerous FOIA requests [10] and to our Citizen Petition. In addition, the loss of FDA experts with knowledge of the regulatory and legislative history of homeopathic medicines since the passage of the FD&C Act is an ongoing problem and is evident in the Agency’s new policy.
FOIA Requests Reveal No Safety Issues with Homeopathic Medicines
We are in full support of the FDA’s vital role in the enforcement of manufacturing and labeling requirements; however, the Agency has painted an unwarranted picture regarding the risks of homeopathic medicines and has diverted limited enforcement resources to non-issues as exhibited in the Import Case. AFHC has repeatedly asked the FDA for evidence of harm using multiple Freedom of Information Act (FOIA) requests. The information the FDA has provided to AFHC actually demonstrates substantial evidence of the safety of homeopathic medicines. The only two examples that the FDA has specifically cited in the guidance to assert safety concerns are related to manufacturing and labeling issues, for which the FDA has an extensive and aggressive inspection program for all homeopathic manufacturers. These issues would not have been corrected by any premarket approval process. The products in question did NOT meet HPUS standards as the FDA claims, and in fact the product accounting for the overwhelming majority of ADRs was mislabeled as homeopathic. [11] FDA traced its concern regarding the other product to a manufacturing issue. [12] Neither product is reflective of the safety record of genuine homeopathic medicines which, when made in accordance with Current Good Manufacturing Practice (CGMP) and homeopathic standards for strength, quality, and purity, have a unique and unchanging safety profile without concerns for toxicity. While Mr. Tantillo’s letter asserts otherwise, the HPUS does, in fact, stipulate a minimum dilution for each individual substance as part of a rigorous process to evaluate the safety and homeopathic indications of each medicine. [13]
Guidance Results in Misapplication of Enforcement Actions
The manufacturing and labeling issues the FDA flagged with products improperly labeled as homeopathic are completely unrelated to the safety and benefits of genuine homeopathic medicines. Furthermore, these issues would not have been prevented or identified by any premarket approval process which is the solution the FDA is proposing in the guidance to address these issues. As Dr. Janet Woodcock stated in 2017, “It’s important that homeopathic products can stay within those guardrails of what makes them safe even if they’re not tested in the way that prescription or OTC products might be. They’re safe because they don’t have pharmacological activity in their product … and we’re more or less willing to concede that for many, many years.” [14] We agree with Dr. Woodcock and fully support ensuring homeopathic manufacturers stay within the guardrails in the law.
However, as illustrated in the Import Case, staying within the guardrails is not a factor in the FDA’s undefined risk-based approach which is resulting, perhaps inadvertently, in a misapplication of enforcement actions against genuine homeopathic medicines. While the homeopathy community doesn’t use or define the term “traditional homeopathy,” senior FDA officials have used the term in our discussions, and we understand it to mean products that meet manufacturing and labeling requirements and therefore can be easily distinguished using the standards in the law. [15] With regards to any vaccine products, vaccines are regulated as biologics and are therefore not included in the HPUS. Any product labeled as homeopathic marketed as a vaccination falls under misbranding, another issue not prevented by any premarket approval process.
No FDA Document Outlining General Risk-Based Approach
Central to the guidance is the new policy’s basis in the Agency’s general risk-based approach to regulatory and enforcement action. AFHC has repeatedly requested through various channels any documentation that outlines the agency’s general principles and overall standards for constructing a risk-based enforcement approach for the many categories of products the agency regulates. The FDA liaison specifically assigned by the FDA to work with AFHC stated that she is “not aware” of any such document. [16] We also requested this information through Congressional offices and a FOIA request and have not received any information that defines what constitutes a risk to consumers both across and within the many categories of products the FDA regulates.
The Import Case exemplifies how a risk-based policy sounds reasonable on its face but requires a comprehensive framework to identify and manage risk within a given product category such as homeopathic medicines. All of the evidence provided by the FDA supports the conclusion that ONLY those products that violate CGMP and homeopathic standards for strength, quality, and purity and which thus cannot legitimately be labeled as homeopathic pose a potential risk to public health. [17] In other words, we would expect the risk-based priorities in a guidance on homeopathic medicines to be centered around improper labeling and/or manufacturing. Yet, as seen in the Import Case, the misapplication of enforcement actions based on generic risk-based categories in the guidance is now leading to the arbitrary removal of genuine homeopathic medicines from the market with no recourse available to the manufacturer for correction and reintroduction.
Guidance Permanently Removes Homeopathic Medicines from the Market
Despite no safety issues with genuine homeopathic medicines, the guidance seeks to permanently remove these medicines from the market by reclassifying them as “unapproved new drugs” requiring pharmaceutical-specific premarket approval. This means the medicines are considered illegally marketed and subject to withdrawal at any time without notice. Such a determination, based on FDA’s new interpretation of the law via guidance, creates a regulatory blind alley for homeopathic manufacturers and is contrary to the intent of the FD&C Act and the 83-year history of how that law has been applied.
As the FDA has correctly stated, the inclusion of the HPUS in the FD&C Act “exempted homeopathic products from safety review” taking into account the diluted nature of such medicines and “the law gives the FDA no pre-market review of true homeopathic dilutions.” [18] The Agency further notes that, “the 1962 drug amendments left the homeopathic exemption intact.” [19] Additionally, the premarket approval process, designed to regulate novel, potentially dangerous drugs containing pharmacologically active chemicals, is not appropriate for homeopathic products due to the unique safety profile and individualized use of the medicines. The expanded premarket approval requirements of the 1962 amendments, Congress’ response to a dangerous pharmaceutical drug tragedy, set forth an expensive process of controlled safety and efficacy studies for pharmaceutical drugs. [20]
No Conditions Provided Under Which Homeopathic Medicines May Be Marketed
Based on the text of the guidance and the FDA’s recent enforcement actions, the “unapproved new drug” designation has the sole effect of removing homeopathic products from the market— products that meet FDA manufacturing and labeling requirements, benefit the health of individuals, [21] and pose no risk as revealed by the materials provided to AFHC by the FDA. If the FDA’s concern is the premarket approval process for homeopathic medicines, we would expect a regulation promulgated in accordance with the law’s recognition of the separate provisions and uniqueness of homeopathic medicines. Instead, as shown in the Import Case above, the guidance results in the removal from the market of safe products used by millions of Americans, limits consumer choice in health care, and fails to outline conditions under which homeopathic medicines may be legally manufactured and marketed. This contravenes the law and raises serious concerns about the future stability of the market and the quality and availability of homeopathic medicines.
AFHC Seeks a Sound Regulatory Framework Ensuring Consumer Access and Safety
Our goal is to work with Congress and the FDA to ensure both consumer access and safety of homeopathic medicines. To achieve these goals we seek to reaffirm the longstanding, clear distinction in the law between homeopathic medicines and pharmaceutical drugs and to reprioritize FDA enforcement actions to distinguish between products in compliance with CGMP and homeopathic standards for strength, quality, and purity (genuine homeopathic medicines with no reasonable possibility of risk) and those that may be adulterated, misbranded, or improperly labeled as homeopathic (and therefore pose a potential risk to public health). Congress and the FDA have considered the unique nature of homeopathic medicines throughout the history of drug regulation under the FD&C Act. We seek to preserve this understanding to ensure continued access to genuine homeopathic medicines.
[1] Goldberg, Burton, Larry Trivieri, and John W. Anderson. “Homeopathy.” Alternative Medicine: The Definitive Guide. Berkeley: Celestial Arts, 2002. Print.
[2] The following illustrate homeopathy’s eminence and distinction across the world as affordable health care: In 2011, the Swiss Government performed a comprehensive review of homeopathy, finding that “it can be said that there is sufficient evidence for the preclinical effectiveness and the clinical efficacy of homeopathy and for its safety and economy compared to conventional treatment.” (Matthiessen, B., Homeopathy in Healthcare. Effectiveness, Appropriateness, Safety, Costs. Springer. 2011). In 2020, German health insurance analysts found that the primary health effectiveness outcomes for patients after six months of homeopathic care were statistically significant in favor of homeopathy over conventional care for: migraine or headache, asthma, dermatitis, and depression. (https://bmchealthservres.biomedcentral.com/articles/10.1186/s12913-020-05706-4). In 2020, the Swiss health insurer SECURVITA released data on 15,700 patients treated homeopathically, comparing this group to an equally large number receiving conventional care. They found that those receiving homeopathic care fared significantly better and needed fewer conventional drugs than those not receiving homeopathic care.This fact was true for children and adults suffering from a wide range of ailments. (https://www.securvita.de/fileadmin/inhalt/dokumente/auszuege_SECURVITAL/202004/securvital_0420_6-11.pdf).
[3] Junod, Suzanne White, An Alternate Perspective: Homeopathic Drugs, Royal Copeland, and Federal Drug Regulation, 55 Food and Drug L.J. 161 (2000).
[4] Medinatura, Inc. v. FDA, 496 F.Supp.3d 416, 431 (D.D.C. 2020).
[5] Id.
[6] In 2015, FDA initiated rulemaking procedures for addressing the regulatory framework for homeopathic medicines but never completed it and instead issued guidance in 2017.
[7] See Syncor Int’l Corp. v. Shalala, 127 F.3d 90, 94 (D.C. Cir. 1997); Food and Drug Admin., Talk Paper No. T-88-68 (Sept. 15, 1988).
[8] This includes comments on dockets FDA-2015-N-0540, FDA-2017-D-6580, FDA-2018-P-2962, and FDA-2020-P-1510.
[9] Docket No. FDA-2020-P-1510; available at https://www.regulations.gov/document/FDA-2020-P-1510-0002.
[10] Between December 2019 and July 2021, AFHC has submitted 4 FOIA inquiries containing 31 specific requests, and the FDA has responded fully to two and only partially to two more of the 31. Evidence to support the FDA’s claims of harm by genuine homeopathic medicines remain unsubstantiated.
[11] FDA Adverse Event Reporting System
[12] https://www.fda.gov/drugs/information-drug-class/laboratory-analysis-homeopathic-teething-tablets.
[13] Homeopathic medicines are diluted to levels that are nontoxic by a very large margin of safety. As part of the evaluation process for inclusion in the HPUS, a First Safe Dilution (FSD) is determined for each substance considering the following categories of information: Single Dose (Acute) Toxicity, Repeat Dose (Chronic) Toxicity, Genotoxicity, Carcinogenicity, Reproductive and Developmental Toxicity, Local Tolerance, Antigenicity, Immunotoxicity, and Addiction Potential. Upon calculation, the resulting FSD is at least 100 times less concentrated than the calculated lowest quantity that might cause an adverse event in a 10 kg child who ingested an entire consumer package. In practice, this means that a child would have to swallow 100 bottles of a homeopathic medicine all at once to approach a level that might cause an adverse reaction.
[14] Wang, Beth. “Drug Center Chief Calls Out Homeopathic Industry.” InsideHealthPolicy.Com’s FDA Week 23, no. 20 (2017): 4–5.
[15] The Food, Drug, and Cosmetic Act (FD&C Act) recognizes as official the drugs and standards in the Homeopathic Pharmacopeia of the United States (HPUS) and its supplements. With the passage of the FD&C Act, the FDA supported including the HPUS and its supplements in the Act to give it the tools to regulate homeopathic medicines as a unique and separate category of drugs. The Act provides the FDA with the authority to enforce standards that separate and safeguard legitimate homeopathic products while permitting swift action against products that are adulterated, misbranded, or improperly labeled as homeopathic. Within this framework the FDA is able to ensure both consumer access and safety.
[16] The FDA liaison responded to AFHC on November 22, 2019 with the following: “I am not aware of another document, aside from the unapproved drugs guidance which you cite below, that explicitly describes our general risk-based approach to enforcement. It is implicit in the enforcement actions we take, and of course described in the unapproved drug guidance.”
[17] In 1983, the FDA finalized an amendment to a proposed regulation, applying certain good manufacturing practice rules to drugs, saying that: “…the Agency believes that the quality controls required by the other portions of the CGMP regulations and the requirements of “The Homeopathic Pharmacopoeia of the United States” are sufficient to ensure the quality of homeopathic drug products.” 48 FR 14004 (April 1, 1983).
[18] Food and Drug Admin., Talk Paper No. T-88-68 (Sept. 15, 1988).
[19] Id.
[20] As of 2018, drug trial costs for FDA approval have an estimated median cost of $19 million—just less than 1% of the estimated $2 to $3 billion average total cost of developing a new drug. (Johns Hopkins, Bloomberg School of Public Health, News Release, September 24, 2018).
[21] The distinguished Swedish medical researcher, Robert Hahn MD, Ph.D., (not connected to homeopathy and not a homeopathic doctor) sought to objectively examine all the available evidence on the topic, and found that, “To conclude that homeopathy lacks clinical effect (as some special interests claim), more than 90% of the available clinical trials would have to be disregarded.” (Hahn, R.Homeopathy: Meta-Analyses of Pooled Clinical Data. Forsch Komplementmed 2013;20:376–381).