Hyland’s “4 Kids Complete Allergy” homeopathic preparation (not for use with food allergies), one of many unregulated, unproven over-the-counter preparations sold in the United States
The FDA announced recently that it is holding a public hearing on April 21 and 22,
to obtain information and comments from stakeholders about the current use of human drug and biological products labeled as homeopathic, as well as the Agency’s regulatory framework for such products. These products include prescription drugs and biological products labeled as homeopathic and over-the-counter (OTC) drugs labeled as homeopathic. FDA is seeking participants for the public hearing and written comments from all interested parties, including, but not limited to, consumers, patients, caregivers, health care professionals, patient groups, and industry.
It’s about time. We know that homeopathic remedies are not, and cannot be, effective. I will not plough that ground again here. Unfortunately, the FDA does not have any authority to bar these fraudulent products from sale altogether. Only Congress can do that.
In this post, I review the current regulatory framework for homeopathic products. I then explore the possibilities, given the opportunities for regulatory change presented by the FDA at this time. In doing so, I answer some of the questions posed by the FDA in its formal notice of the hearing, printed in the Federal Register.
I argue that the FDA has no statutory authority for the manner in which it currently regulates (or, actually, doesn’t regulate) homeopathic drugs. I further argue this system, largely controlled by the homeopathic industry, must be abandoned, and that there is no reason why homeopathic drugs should not be regulated just like any other OTC or prescription drug.
(Note to those wanting to submit written comments or attend the hearing: there are deadlines and other requirements for participation. You can read those in the Federal Register.)
History
The original Food, Drug and Cosmetics Act (FD&C Act), passed in 1938, authorized the FDA to demand evidence of safety for new drugs, issue standards for food, and conduct factory inspections. Significant to our purposes here, the Act was directed in part at quacks selling adulterated and misbranded remedies throughout the U.S., with little fear of reprisal.
The Kefauver-Harris Amendments of 1962 strengthened the rules for drug safety and, for the first time, required manufacturers to prove their drugs’ effectiveness. In 1992, the FD&C Act was amended again to require the drug industry to bear part of the considerable expense of the drug approval process.
Under the FD&C Act, the definition of “drug” includes:
- Articles recognized in the official United States Pharmacopoeia (USP), official Homoeopathic Pharmacopoeia of the United States (HPUS);
- articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and
- articles (other than food) intended to affect the structure or any function of the body of man or other animals.
A homeopathic drug can fall within any of these categories. It can also fall within the definition of a “biologic” under a different federal statute making these products subject to FDA regulation. However, we’ll stick to drugs here.
In the FDA’s own estimation,
the FDA . . . ensures the safety and effectiveness of all drugs [and] biological products . . .
That statement is not entirely true. By its own admission, the FDA does not ensure the safety and effectiveness of homeopathic remedies.
Yet, the FDA’s position is now, and always has been, that nothing in the FD&C Act exempts homeopathic drugs from any approval, adulteration, and misbranding provisions (including labeling requirements) of federal law.
Why, then, does the FDA not require that homeopathic drugs be proven safe and effective prior to marketing? Why has the FDA, in the words of one federal district judge,
largely abdicated any role it might have had in creating standards for homeopathic OTC [over-the-counter] drugs, and has instead attempted to delegate this authority to the non-governmental organization that determines whether homeopathic substances should be included in the HPUS. In addition, the FDA explicitly states that it makes no guarantee about the safety or efficacy of homeopathic OTC drugs even if they meet the unknown standards for inclusion in the HPUS.
(Although the judge was talking about OTC homeopathic drugs, the same is true for the tiny percentage [about 5%] of homeopathic drugs that are prescription only.)
The FDA, like any federal agency, must act only within the authority granted it by Congress. The FDA does not cite any statutory authority for these decisions, and my research didn’t disclose any. It may well be that the FDA, in fact, has no legal authority for its neglect of homeopathic drug regulation.
There are apparently historical reasons for this neglect. For many years, most homeopathic products required a prescription and there were few homeopathic practitioners to write them. There were only a handful of established firms making homeopathic remedies. The FDA had limited resources and did not consider homeopathic products much of a safety risk. Yet, when it did finally act, what it created was, in the view of some, a recipe for a booming OTC homeopathic remedy market.
(For a more complete review of the history of homeopathic drug regulation, or the lack thereof, see Junod SJ. “An Alternative Perspective: Homeopathic Drugs, Royal Copeland, and Federal Drug Regulation,” 55 (1) Food Drug L.J. 161-83 (2000), PMID 12375600, from which I learned the historical reasons for the FDA’s forbearance.)
Since 1988, both prescription and OTC homeopathic drugs have been manufactured and sold without FDA approval under enforcement policies set out in the FDA’s Compliance Policy Guide (CPG) 400.400, “Conditions Under Which Homeopathic Drugs May be Marketed.” This 7-page document pales in comparison to the FDA pre- and post-market regulation of all other drugs and biologics. It basically covers only labeling.
CPGs are not are not regulations or laws and are not enforceable. They merely represent FDA thinking on a particular subject. Most importantly, they do not create or confer any rights for or on any person and do not bind the FDA or the public.
The FDA has now come to question whether this bare-bones guidance is sufficient. The agency cites several reasons for this.
- The explosive growth in the OTC homeopathic remedy market. In 2007, Americans spent about $2.9 billion on the purchase of homeopathic medicine. They are being marketed as “natural, safe, and effective alternatives to other prescription and non-prescription products.”
- Homeopathic drugs can contain a wide range of substances, including ingredients derived from plants, healthy or disease animals or human sources, minerals and chemicals. These can cause, and have caused, side effects. In 2012, there were over 10,000 reported “poison exposure cases” related to homeopathic agents, the vast majority of those attributed to children 5 and under, some of which required medical treatment.
Q & A
FDA has a list of questions in the Federal Register and encourages comments on these and other matters related to homeopathic remedies. We’ll address several of the questions here.
What are consumer and health care provider attitudes towards human drug and biological products labeled as homeopathic?
Consumers are obviously buying homeopathic remedies because they think they are safe and effective. Otherwise, why would they spend the money and ingest these substances or give them to their families? Yet, they have no reliable, objective information on which to make these decisions. (The internet is rife with unproven claims for homeopathic products.) The only source of label information is from those who are financially interested in the sale of homeopathic products.
Although I do not have statistics, naturopaths are likely the most common prescribers of homeopathic products. There are too few professional homeopaths in practice to account for much of the market and conventional medical providers widely disparage homeopathic remedies. Naturopaths, along with chiropractors and acupuncturists, regularly sell homeopathic products to their patients, giving them a financial interest that is in conflict with their ability to objectively evaluate these remedies.
The opinion of health care practitioners and scientists in general, other than the CAM practitioners just mentioned, is near-universally negative and long-standing. In fact, there are humorous videos widely available on the internet making fun of homeopathy. I will not attempt to catalog the massive amount of evidence that homeopathic remedies are no more effective than placebo, the most recent compilation of which can be found in the Australian National Health and Medical Research Council’s Statement and Advice on Homeopathy. No responsible scientist claims otherwise. The FDA is no doubt aware of the research. I do note, however, that the American Pharmacists Association is also calling for adequate regulation in their policy on homeopathy:
APhA supports the demonstration of safety and efficacy of homeopathic products from adequate, well-designed scientific studies before pharmacists advocate or sell homeopathic products. . .
APhA supports the modification of the Food, Drug and Cosmetic Act to require that homeopathic manufacturers provide evidence of efficacy and safety for all products, including products currently in the marketplace.
(Actually, no such modification is necessary as the authority is, and always has been, contained in the FD&C Act and amendments thereto.)
I expect many other voices to join the call for adequate regulation during this process.
Are the current enforcement policies under the CPG appropriate to protect and promote public health in light of the tremendous growth in the homeopathic drug market? Are there alternatives to the current enforcement policies?
No, the CPG is not appropriate. It is wholly inadequate. Yes, there are alternatives.
Actually, the answer to this question is fairly simple. There is no statutory authority in the FD&C or subsequent Acts to carve out an exception for homeopathic drugs, which is essentially what the FDA has done with CPG 400.400. The CPG basically addresses only labeling. It does not require demonstration of safety or efficacy, despite being clearly required by federal law.
In fact, the FDA has abdicated its authority to the Homeopathic Pharmacopoeia Convention of the United States, a private organization answerable to no one, to decide what homeopathic drugs are on the market. The HPCUS is rife with conflicts of interest. Decisions on the content of the HPUS are made by either practicing homeopaths, homeopathic pharmacists, or current or former officials or owners of homeopathic products manufacturing companies. It is totally controlled by industry insiders. One can only imagine the outcry if a similar organization of Big Pharma companies were calling the shots in deciding which drugs made it to market.
Apparently, the HPCUS believes it is a lawful substitute for the Agency in the drug approval process. An industry representative active in the HPCUS claims that:
Instead of the [FDA’s] new-drug-approval process [for all other drugs], premarket approval for homeopathic drugs is by way of monograph approval by HPCUS. While homeopathic drugs are subject to the FDA’s nonprescription drug review, FDA has not yet used this authority . . .
In fact, Congress has most certainly not given the HPCUS authority to grant pre-market approval. Nor is the FDA’s authority limited to “nonprescription drug review.”
The only solution is to employ the same regulatory scheme for homeopathic drugs as the FDA uses for other prescription and non-prescription drugs. Federal law requires no less.
A large majority of human drug products labeled as homeopathic are marketed as OTC drugs. These products are available for a wide variety of indications, and many of these indications have never been considered for OTC use under a formal regulatory process. What would be an appropriate regulatory process for evaluating such indications for OTC use?
There is no reason the FDA’s formal regulatory process applicable to other OTC drugs should not be employed for homeopathic drugs. Fortunately, there is precedent for a post-market review to bring homeopathic OTC drugs in line with federal law. In fact, this very process is outlined in the FDA’s announcement in the Federal Register.
In 1972, the FDA undertook a massive review of all OTC drugs (and an estimated 100,000 to 500,000 separate ingredients) to determine which could be classified as safe and effective and not misbranded. In accordance with amendments to the FD&C, the FDA was to determine which OTC drugs are generally recognized among qualified experts as safe and effective and not misbranded under prescribed, recommended, or suggested conditions.
However, at the request of homeopathic trade groups, homeopathic remedies were deferred from review. The FDA never returned to the task and OTC homeopathic drugs have never been reviewed by the FDA for safety and efficacy.
There is no reason the FDA should not take up where it left off. A caveat is in order here. While the FDA may feel obligated to include homeopathic proponents among the reviewers, the FDA should not let the proponents have the final say. Nothing in federal law suggests that Congress intended to incorporate the homeopathic industry’s pseudoscientific notions or its low quality studies into law. If the FDA feels otherwise – that it is somehow beholden to prescientific ideas and widely discredited treatments because of Congress’s reference to the HPUS – it can simply proceed under the authority granted it pursuant to the second and third definition of “drug” in the FD&C Act.
Do consumers and health care providers have adequate information to make informed decisions about drug products labeled as homeopathic? If not, what information, including, for example information in labeling, would allow consumers and health care providers to be better informed about products labeled as homeopathic?
No, they do not have adequate information. For one thing, unlike the vast amount of drug information available free to the public on the FDA’s website, there is no objective, substantive, publicly-available homeopathic drug information. The HPUS can be accessed only through an expensive paywall, the proceeds of which go to the HPCUS. Simply following the rules for other OTC drugs, including the transparency legally required in this process, would go a long way toward helping the consumer become better informed.
As a thought exercise, let’s examine the information available on the website of Hyland’s, a homeopathic remedy manufacturer, about one of its homeopathic remedies versus what an OTC label would require if it were not a homeopathic remedy. I am using the website information on the assumption that it is the same as that given on the label. (Actually, in using Latin terms, Hyland’s appears to be violating even the minimal requirements of CPG 400.400.)
According to Hyland’s, its “4 Kids Complete Allergy” is a “safe, effective formula for children 2-12 years old.” The only warning is that it should not be used to treat food allergies. The product, according to the website,
temporarily relieves the symptoms of hay fever, indoor and outdoor allergens including itchy nose and throat, itchy watery eyes, runny nose, sneezing and sinus pain.
There is no statement that these claims have not been evaluated by the FDA, which is not required for OTC drugs, because any other OTC product would, in fact, have been evaluated by the FDA.
Active ingredients, their homeopathic dilution and their purposes are listed as:
- Acontium Napellus 6X HPUS: itchy throat, sneezing
- Allium Cepa 6X HPUS: hay fever, runny nose, watery, itchy eyes
- Euphrasia 6X HPUS: irritated eys, nasal discharge
- Galphimia Glauca 12X HPUS: sneezing, runny nose
- Histaminum Hydrochloricum 12X HPUS: ear and nose discomfort
- Luffa Operculata 12X HPUS: sinus pain, headache
- Natrum Muriaticum 6X HPUS: runny nose, itchy irritated eyes
- Nux Vomica 6X HPUS: stuffy nose
- Pulsatilla 6X HPUS: sinus pressure
- Sabadilla 6X HPUS: hay fever, sneezing
I could not find information about what these substances are, or what 6X or 12X HPUS means, anywhere on the Hyland’s website. In fact, it took a good deal of searching to find this information on the internet. Anyone who did not have prior knowledge of homeopathic dilutions, like I do, would presumably encounter even more difficulty.
If this remedy were regulated like other OTC drugs, Hyland’s could never make the claim that its “4 Kids Complete Allergy Relief” is safe and effective without having gone through the FDA approval process. Nor could it make the “uses” claims. However, putting those substantial barriers to the sale of this product aside, what would an OTC label otherwise require if homeopathic products weren’t exempted by the FDA?
Here’s my interpretation of what the Active Ingredients list would look like, based on my internet search. Of course, the FDA requires standardized label information for all OTC products and the end result would likely be far more informative than my attempt at revision, but we’ll give it a go.
- Aconite (a poisonous plant)
- Onion
- Eupharsia (a genus of about 450 species of herbaceous flowering plants in the family Orobanchaceae)
- Galphimia glauca (a plant)
- Histaminum Hydrochloricum (a chemical made from histamine dihydrochloride, trade name Ceplene, a salt of histamine which is used as a drug)
- Luffa (a plant, most commonly used, in dried form, as a skin exfoliator)
- Table salt (sodium chloride)
- “Strychnine tree” (a major source of the highly poisonous, intensely bitter alkaloids strychnine and brucine)
- Pulsatilla (a plant)
- Sabadilla (Schoenocaulon officinale, a plant, parts of which are used as an insecticidal dust; toxic to honeybees.)
Homeopathic dilutions used in this product:
6X = one part of ingredient to 1,000,000 parts of water
12X= one part of ingredient to 1,000,000,000,000 parts water
I could not find any indication that many of these ingredients have been proven safe and effective for anything in any amount, and none at these dilutions. Some are downright dangerous.
It would be ludicrous to argue that a parent choosing an allergy symptom remedy for his child would not think this information is important. Yet such is the current regulatory framework for homeopathic remedies.
In sum, the FDA already has in place a well-established regulatory system for prescription and OTC drugs. There is no reason to exclude homeopathic drugs from this process any longer.
