The origins of FDA’s CPG 400.400 go back to a series of meetings between industry and Agency enforcement personnel in the 1980s. The resulting CPG was unusual in that many of the provisions were simply a restatement of existing statutory or regulatory requirements, but their inclusion may have been due to FDA’s recognition that much of the industry had little understanding of FDA regulatory requirements. The CPG also provided some education about homeopathy for FDA personnel. Entitled “Conditions Under Which Homeopathic Drugs May be Marketed,” CPG 400.400 contained key definitions, including:
- A definition of “homeopathic,”;
- Reference resources for traditional uses of homeopathic drugs, such as A Dictionary of Practical Materia Medica by John Henry Clarke, M.D., (3 volumes; Health Science Press) and A Clinical Repertory to the Dictionary of Materia Medica by John Henry Clarke, M.D. (Health Science Press);
- How to handle instances in which the active ingredient was not included within the HPUS;
- Recognition of the different way in which the strength of homeopathic active ingredients are declared (e.g., 10X, 20X, 10C); and
- A recitation of statutory and regulatory labeling requirements.
CPG 400.400 led to major changes in the homeopathic industry. Prior to 1988, the only indication on the label of most homeopathic drugs was, “Use according to standard homeopathic indications.” While that fit well with the symptom-based approach at the core of homeopathy, FDA was unwilling to permit that approach to continue, insisting that the statute required a specific indication, and the CPG restates that position. The addition of indications familiar to consumers to homeopathic labels aided many consumers as they sought alternatives to other available medicines.
The policy legacy of the Drug Efficacy Amendments of 1962 caused FDA to consider the safety and efficacy of medicines in general but to accomplish it efficiently. The Compliance Policy Guide was FDA’s effort to address a market of modest size that included a large range of products. How did the CPG do?
Twenty-nine years of experience with CPG 400.400 is an adequate timeframe from which to evaluate its success from a health agency policy standpoint.
Potential policy objectives:
- Aid informed choice among consumers facilitating access to a safe and popular therapeutic modality.
- Reduction of products promoted for disease claims not amenable to self-treatment.
- Reduction of unapproved combinations of homeopathic and non-homeopathic ingredients.
- Accomplish these policy objectives with resources that are proportional to the risks to consumers and the market size.
Compliance Policy Guide 400.400 required that homeopathic medicines bear at least one major indication for use. At the publication of the CPG, most combination products were labeled with an indication for use. As mentioned above, single ingredient homeopathic products were often labeled with a statement like “For standard homeopathic indications.”
Complying with the major indication rule on single ingredient medications allowed retailers to move singles into self-service setting. Single ingredient medicines moved from behind the counter onto shelves accessible to consumers. Self-service merchandising inspired the development of promotional materials and activities among manufacturers leading to even more information available to consumers.
In short, the CPG achieved the policy goal of aiding informed choice among consumers.
Serious disease claims on homeopathic drug products
The CPG was published at a time that many labelers of homeopathic drug products had limited understanding of FDA’s regulatory requirements. Labelers interpreted the CPG to mean that the principle indication for use must be directly referenceable to the historic homeopathic medical literature mentioned within the CPG. Because of this understanding, many products came to market with indications written in 19th-century medical language which was difficult for consumers to understand.
AAHP conducted a survey of members in preparation for the FDA Part 15 hearing on homeopathic drug product regulation in April of 2015. That survey revealed that 64% of members use the wording of the OTC monographs when evaluating indications for use on their product labels.1 Similarly AAHP reported that on review of FDA’s drug listing database revealed that of the listing that were evaluable 53.5% of indications for use on listed products were either a monograph indication or otherwise amenable to self-medication. 2
Because we don’t have a starting point of comparison it is difficult to know how much progress in disease claims was made on homeopathic labels over the 29 years of the CPG’s existence. What can be said is, without the CPG, many fewer products would have indications at all.
Combinations of homeopathic and other ingredients
In the Compliance Policy Guide FDA said: “Drug products containing homeopathic ingredients in combination with non-homeopathic active ingredients are not homeopathic drug products.” FDA’s policy objective for including this statement was to avoid potentially unsafe combinations of homeopathic and other active ingredients or combinations of homeopathic active ingredients and dietary supplement ingredients.
AAHP has not conducted a detailed study of enforcement action against non-compliant combinations of homeopathic and other ingredients. However, it is safe to say however that combinations of these types do exist today in the market-place although at a level that is not stimulating enforcement action.
Resources proportional to the risks to consumers and the market size.
Over the 29-year life span of the Compliance Policy Guide 400.400 FDA has dedicated remarkably few resources to the surveillance and enforcement of homeopathic drug products. In the early days of the CPG, FDA made available a liaison to the homeopathic industry. CSO Ed Miracco was our Liaison. Ed was available to answer questions and he conducted several labeling seminars. In total over the roughly 10 years that he was active I would be hard to believe Ed dedicated more than a few weeks of his time to homeopathy. There were no subsequent liaisons.
The number and scope of surveillance inspections between 1988 and 2010 were limited to GMPs. Very few, if any, warning letters were written prior to 2008. Beginning in 2008 however FDA surveillance inspections, product inspections, warning letters and import alerts increased. In all however, enforcement actions against homeopathic products or manufacturers never exceeded 10 in any one year3.
FDA invested little resources in the surveillance and enforcement of homeopathic drug products. It was not before 2010 that FDA began to increase enforcement against the category. In short, The CPG was very successful at meeting the policy goal of Resources proportional to the risks to consumers and the market size.
FDA Compliance Policy Guide 400.400 was successful on all policy objectives.
Informed Consumer Choice The CPG requirement of Indications for use resulted in a manyfold increase in information available to consumers.
Serious disease claim reduction At the end of its life CPG 400.400 resulted in 64% of surveyed labelers referring to regulatory text when deciding on labeling claims.
Non-compliant combinations Although non-compliant combinations exist within the market, they are generating minimal enforcement activity at this time.
Resources proportional to risk FDA dedicated very limited resources to homeopathic drugs over its 29-year life span.