Homeopathic Drug 
Products  
Guidance for FDA Staff 
and Industry
  
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
 
 
 
December 2022 
Compliance
   
 
Homeopathic Drug 
Products  
Guidance for FDA Staff 
 and Industry 
 
 
Additional copies are available from: 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs  
 
and/or 
 
Office of Communication, Outreach and Development  
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993-0002 
Phone: 800-835-4709 or 240-402-8010 
Email: ocod@fda.hhs.gov 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
December 2022 
Compliance 
   
TABLE OF CONTENTS 
 
I.  INTRODUCTION ........................................................................................................................... 1 
II.  BACKGROUND ............................................................................................................................. 1 
A.  Compliance Policy Guide 400.400 ..................................................................................... 3 
B.  FDAs Reexamination of its Enforcement Policies ............................................................ 3 
C.  FDAs Risk-based Approach .............................................................................................. 4 
III.  FDAs ENFORCEMENT POLICY ................................................................................................. 4 
   
  Contains Nonbinding Recommendations 
Homeopathic Drug Products  
Guidance for FDA Staff and Industry1 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the 
title page. 
 
 
 
I.  INTRODUCTION 
 
This guidance describes how we intend to prioritize enforcement and regulatory actions for 
homeopathic drug products2 marketed in the United States without the required FDA approval.  
As discussed below, FDA has developed a risk-based approach under which the Agency intends 
to prioritize enforcement and regulatory actions involving certain categories of such products 
that potentially pose a higher risk to public health.  
 
The Agency anticipates that many homeopathic drug products will fall outside the categories of 
drug products that FDA intends to prioritize for enforcement and regulatory action as described 
in Section III below. 
 
For the purposes of this guidance, we define a homeopathic drug product as a drug product 
that is labeled as homeopathic, and is labeled as containing only active ingredients and 
dilutions (e.g., 10X, 20X) listed for those active ingredients in the Homeopathic Pharmacopeia of 
the United States (HPUS).3 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required.  
 
II.  BACKGROUND 
 
Homeopathy is an alternative medical practice that has a historical basis in theory and practice 
first systematized in the late 1700s.  Homeopathy is generally based on two main principles: (1) 
 
1 This guidance has been prepared by the Center for Drug Evaluation and Research in cooperation with the Center 
for Biologics Evaluation and Research at the Food and Drug Administration. 
2 For the purposes of this guidance, references to drugs and drug products (including homeopathic drug products) 
include biological products as defined in section 351 of the Public Health Service Act (42 U.S.C.  262). 
3 A product that conforms to the HPUS dilution standards may still fall under the enforcement priorities described in 
section III below.  
1 
  Contains Nonbinding Recommendations 
that a substance that causes symptoms in a healthy person can be used in diluted form to treat 
symptoms and illnesses (known as like-cures-like); and (2) the more diluted the substance, the 
more potent it is (known as the law of infinitesimals).  Proponents claim that a significantly 
diluted aqueous solution, consisting mainly of water molecules, retains therapeutic properties 
due to a memory of the substance diluted in it.  Historically, homeopathic drugs have been 
identified through provings, in which substances are administered to healthy volunteers in 
concentrations that provoke overt symptoms.  Symptoms experienced by volunteers are recorded 
to indicate possible therapeutic uses for the substances.  In other words, if a substance elicits a 
particular symptom, individuals experiencing that symptom would be treated with a diluted 
solution made from that substance. 
 
In 1938, when the Federal Food, Drug, and Cosmetic Act (FD&C Act) was enacted, the bills 
senatorial sponsor, Dr. Royal Copeland, himself a homeopathic practitioner, added a provision to 
the law recognizing the HPUS alongside its counterparts, the U.S. Pharmacopeia (USP) and the 
National Formulary (NF).4  Recent years have seen an increase in the sale of homeopathic drug 
products.  In the past, these products were mostly prepared by homeopathic physicians for 
individual patients.  Today they are frequently mass manufactured and widely marketed as over-
the-counter (OTC) products.  
 
The definition of drug in section 201(g)(1) of the FD&C Act (21 U.S.C. 321(g)) includes, 
among other articles, articles recognized in the HPUS or any of its supplements.  As such, 
homeopathic drugs are subject to the same statutory requirements as other drugs; nothing in the 
FD&C Act exempts homeopathic drug products from any of the requirements related to 
approval, adulteration, or misbranding, including labeling requirements.  Generally, a drug, 
including a homeopathic drug, is considered a new drug if it is not generally recognized as safe 
and effective (GRAS/E) by qualified experts for use under the conditions prescribed, 
recommended, or suggested in the labeling.5   
 
Under section 505(a) of the FD&C Act (21 U.S.C. 355(a)), before any new drug is marketed, it 
must be the subject of an approved application filed pursuant to section 505(b) or section 505(j) 
of the FD&C Act.  The requirements in section 505 of the FD&C Act apply to biological 
products regulated under section 351 of the Public Health Service Act (PHS Act) (42 U.S.C. 
262); however, as stated in section 351(j) of the PHS Act (42 U.S.C.  262(j)), a biological 
product with an approved license under section 351(a) of the PHS Act (42 U.S.C.  262(a)) is not 
required to have an approved application under section 505 of the FD&C Act.  Accordingly, 
absent a determination that a homeopathic drug product is not a new drug under section 
201(p), such a homeopathic drug product is subject to the premarket approval requirements in 
section 505 of the FD&C Act or section 351 of the PHS Act.  There are currently no 
homeopathic drug products that are approved by FDA.  
 
Under section 505G of the FD&C Act (as added by the CARES Act6)which reforms and 
modernizes the OTC drug review process established in 1972FDA now issues administrative 
orders to make GRAS/E determinations for certain nonprescription drugs marketed without an 
 
4 Section 201(g)(1)(A) of the FD&C Act. 
5 Section 201(p) of the FD&C Act.  
6 Public Law 116-136 (March 27, 2020). 
2 
  Contains Nonbinding Recommendations 
approved application.7  Prior to enactment of CARES, FDA had not reviewed any homeopathic 
drug products under the OTC Drug Review, because the Agency had placed homeopathic drug 
products in a separate category and deferred consideration of them.8 Subsequent to enactment of 
CARES, no GRAS/E determinations will be made for homeopathic drug products under section 
505G, because section 505G does not apply to homeopathic drug products.9  Because at this time 
no homeopathic drug products have been determined by FDA to be GRAS/E, all homeopathic 
drug products remain subject to the premarket approval requirements. 
A.  Compliance Policy Guide 400.400 
 
In May 1988, the Center for Drug Evaluation and Research (CDER) issued Compliance Policy 
Guide (CPG) 400.400 entitled Conditions Under Which Homeopathic Drugs May be 
Marketed.  CPG 400.400 described the Agencys enforcement priorities for homeopathic drugs. 
 
B.  FDAs Reexamination of its Enforcement Policies 
 
In light of the growth of the industry and passage of more than 2 decades since the issuance of 
CPG 400.400, FDA announced on March 27, 2015, that it was evaluating its regulatory 
framework for homeopathic drug products.10  In April 2015, FDA held a public hearing to obtain 
information and comments from stakeholders about the current use of homeopathic drug 
products, as well as the Agencys regulatory framework for such products.11  FDA sought broad 
public input on its enforcement policies related to homeopathic drug products in an effort to 
better promote and protect the public health.   
 
Since the issuance of CPG 400.400, the Agency has encountered multiple situations in which 
homeopathic drug products posed a significant risk to patients.  Such products either caused or 
could have caused significant harm, even though the product labeling and ingredient formulation 
appeared to meet the conditions of CPG 400.400.12  FDA has also documented many serious 
violations of Current Good Manufacturing Practice (CGMP) requirements by some 
 
7 In addition, under section 505G(a) of the FD&C Act, certain nonprescription drugs marketed without an approved 
application are deemed GRAS/E and not new drugs if applicable conditions are met. 
8 See 37 FR 9464, 9466 (May 11, 1972). 
9 See section 3853 of the CARES Act, Public Law 116-136. 
10 80 FR 16327, Homeopathic Product Regulation: Evaluating the Food and Drug Administrations Regulatory 
Framework After a Quarter-Century. 
11 Docket No. FDA-2015-N-0540; available at https://www.regulations.gov/docket?D=FDA-2015-N-0540.  
12 For example, in 2016, FDAs search of the FDA Adverse Event Reporting System (FAERS) database identified 
99 cases of adverse events consistent with belladonna toxicity, including reports of infant deaths and seizures, 
possibly related to teething products.  Multiple homeopathic drug products were identified as associated with this 
safety concern.  Further investigation revealed that the poisonous belladonna alkaloids in some of the homeopathic 
teething tablet products far exceeded the labeled amounts, raising a serious safety concern.  As another example, by 
2009, FDA had received more than 130 reports of anosmia (loss of the sense of smell) associated with the use of 
Zicam homeopathic intranasal zinc products.  FDA determined that if the products were used as labeled, a user 
would receive significant daily exposure to intranasal zinc, raising a serious safety concern.  These are only two 
examples among many.   
3 
  Contains Nonbinding Recommendations 
manufacturers of homeopathic drug products, raising significant concerns about the safety of 
products made with inadequate process controls.13  
 
As a result of the Agencys evaluation of its regulatory framework, including consideration of 
the information obtained as a result of the public hearing and the recent growth of safety 
concerns associated with some homeopathic drug products, FDA believes that it is in the best 
interest of public health to issue a new guidance that applies a risk-based enforcement approach 
to homeopathic drug products marketed without the required FDA approval, consistent with 
FDAs risk-based regulatory approaches generally. 
 
C.  FDAs Risk-based Approach 
 
Regardless of the product area, FDA generally applies a risk-based enforcement strategy.  For 
example, FDA has generally employed a risk-based enforcement approach with respect to 
marketed unapproved new drugs.14  The Agency historically has prioritized compliance actions 
involving unapproved new drug products that have potential safety risks, lack evidence of 
effectiveness, are health fraud products, present challenges to the new drug approval process or 
the OTC Drug Review, are violative of the FD&C Act in other ways, or are reformulated to 
evade an FDA enforcement action.  
 
The Agency generally intends to apply a risk-based enforcement approach to the manufacturing, 
distribution and marketing of homeopathic drug products, as described below.   
 
 
III.  FDAs ENFORCEMENT POLICY 
 
FDA is not required, and generally does not expect, to give special notice that a drug product 
may be subject to enforcement action.  In the listing that follows, we clarify our general approach 
to prioritizing our enforcement and regulatory actions with regard to homeopathic drug products 
marketed in the United States without the required FDA approval.  However, this guidance is 
intended to provide notice that any homeopathic drug product that is being marketed illegally is 
subject to FDA enforcement action at any time.   
 
Enforcement and Regulatory Priorities 
 
In developing a risk-based approach, FDA has identified certain categories of homeopathic drug 
products marketed without the required FDA approval as potentially posing higher risks to 
public health.  FDA generally intends to prioritize enforcement and regulatory actions with 
 
13 For example, in 2019, FDA issued Warning Letters to four companies that jointly manufacture and package 
Puriton Eye Relief Drops. The warning letters describe failures to conform to CGMP requirements due to improper 
methods, facilities or controls for manufacturing, processing and packing drugs. For example, multi-dose, 
preservative-free, homeopathic ophthalmic drug products were manufactured without any attempt to render them 
sterile. FDA tested multiple samples of these homeopathic ophthalmic drug products and found that they (1) were 
non-sterile (samples were found to be contaminated with Bacillus spp., high levels of particulate matter, or both), 
which could lead to eye infection; and (2) had a dangerously high pH level, which could lead to eye injury such as 
glaucoma, corneal scarring, and loss of vision. 
14 See 85 FR 28605, 28606 (May 27, 2021). 
4 
  Contains Nonbinding Recommendations 
respect to premarket approval requirements involving homeopathic drug products that are 
marketed without the required FDA approval  that fall within the following categories: 
 
  Products with reports of injury that, after evaluation, raise potential safety concerns.    
For example, MedWatch reports or other information submitted to the Agency can 
indicate or signal a potential association between the product and an adverse event, 
medication errors, or other safety issues.  
 
  Products that contain or purport to contain ingredients associated with potentially 
significant safety concerns. For example, potentially significant safety concerns are 
raised by products that contain or purport to contain: 
  An infectious agent with the potential to be pathogenic; 
o
  A controlled substance, as defined in the Controlled Substances Act, 21 U.S.C. 
o
802; 
  Multiple ingredients that, when used in combination, could result in possible 
o
interactions, synergistic effects, or additive effects of the various ingredients; or, 
  Ingredients that pose a risk of toxic, or other adverse effects, particularly when the 
o
ingredients are concentrated or in low dilution presentations (e.g., 1X, 2X, or 1C), 
or are not adequately controlled in the manufacturing process.  
 
  Products for routes of administration other than oral and topical.  For example, 
injectable drug products and ophthalmic drug products in general pose a greater risk of 
harm to users because the routes of administration for these products bypass some of the 
bodys natural defenses.  In particular, contaminated injectable and ophthalmic products 
can pose serious risks to the patient.   
 
  Products intended to be used for the prevention or treatment of serious and/or life-
threatening diseases or conditions.  Unapproved products for serious and/or life-
threatening diseases or conditions raise public health concerns, in part, because they may 
cause users to delay or discontinue medical treatments that have been found safe and 
effective through the new drug application (NDA) or biologics license application (BLA) 
approval processes. 
 
  Products for vulnerable populations.  For example, patient populations such as 
immunocompromised individuals, infants and children, the elderly, and pregnant women 
may be at greater risk for adverse reactions associated with a drug product, even if it 
contains only small amounts of an ingredient, due to the varying ability of individuals in 
these populations to absorb, metabolize, distribute, or excrete the product or its 
metabolites.  These populations may also be at greater risk of harm as a result of 
foregoing the use of medical treatments that have been found safe and effective through 
the NDA or BLA approval processes or under the OTC Drug Review. 
 
  Products with significant quality issues.  For example, products that are contaminated 
with foreign materials or objectionable micro-organisms, and/or are made in facilities 
with significant deviations from CGMP, pose a significant safety risk to patients. 
5