European Union regulation of elderberry
European Union regulation of elderberry

By Nnenna Udensi, MD

Considered on its medicinal merits, elderberry is currently viewed as a herbal supplement by much of the world. Different countries have varying regulations for vitamins and supplements and governments are interested in how companies market health products to the public. Most governments regulate the types of claims that companies make to the public about a supplements’ effects based on the quantity and quality of the data that back those claims.  In the United States, this role is fulfilled by the Food and Drug Administration (FDA). But in this article I will focus on the European Medicines Agency (EMA) which is the European Union agency responsible for the regulation of elderberry and other medicinal products in the EU.

This article will touch on the herbal medicine branch of the EMA, elderberry’s classification as a medicine in the EU and supporting documents such as the assessment report (EPAR) and EU Monograph for elderberry that are produced by the agency..

Overview of herbal medicine regulatory designations in the EU

The European Medicines Agency (EMA) is the organization responsible for the evaluation of medicinal products in the European Union. When drug companies or researchers want to sell their medications in EU countries, they must submit an application and seek approval from the EMA. There is a branch of the EMA that deals specifically with the approval and classification of herbal medicinal products, such as elderberry, called the Committee for Herbal Medicinal Products (HMPC). Herbal Medicine (medicinal preparations derived entirely from plant sources) is generally considered lower risk and is not subject to the same stringent testing and guidelines that more modern therapies are. Accordingly, this separate EMA branch for herbal products uses a simplified registration procedure.  Herbal medicines are classified under either ‘traditional use’ or ‘well-established use’ as follows:

Traditional use registration

  • Intended for herbal products with a long (30+ years) history of medicinal use that falls short of requirements for “well-established use.”
  • Safety data is sufficient and “plausible” and efficacy is demonstrated. No clinical tests or trials are required for this classification.
  • Medical products in this category are intended for use without medical supervision and are not injectable.
  • Must have been in use for at least 30 years including 15 years in the EU.

Well – established use marketing authorization

  • Assessment of safety and efficacy data
  • At least ten years of scientific literature confirming the product’s active ingredients have been in well-established medicinal use.

Stand-alone/ mixed application

–    Safety and efficacy data from the company’s product development.

The last classification, Stand-alone/ mixed seems to apply when new uses or formulations are found for previously registered generic products. It allows for the product to be marketed for the new use. It does not appear that elderberry can be classified under this category yet.

Elderberry approved as a medicinal product under “traditional use”

Elderberry is currently approved under the ‘traditional use’ registration which makes sense for several reasons including 1) it has been around as a treatment in numerous cultures for centuries, 2) there are clinical trials and a wealth of data establishing its safety, and 3) the efficacy for colds and other viral ailments has been studied repeatedly.

I believe elderberry might be a good candidate for a ‘well-established’ use marketing authorization if it was more widely used. Classification of elderberry under well-established use would bring it into the doctor’s office as potential treatments for approved conditions. Companies that make elderberry products would be able to market them to doctors and patients.  And similar to the way a patent with a cold may be advised to take vitamin c, or someone with a wound might be prescribed zinc supplements; elderberry products would potentially be recommended by doctors with greater frequency, increasing both awareness and data available to be studied.

Unfortunately, while the data clearly establishes that elderberry has some benefit in various conditions, particularly in fighting colds, the magnitude of those benefits is still debatable8,9. Consequently, I believe the medical community tends to proceed with products that have stronger supporting data. That said, the current classification of ‘traditional use registration’ acknowledges elderberry’s potential benefits and allows for it to be consumed as a supplement without medical supervision and to be marketed in the EU as such.

Monographs and assessment reports are helpful to researchers

Apart from its role in classifying medicines, the EMA also maintains a monograph of each drug, and publishes an assessment report. A monograph is a detailed study of a specialized subject and serves as a central source of information on the topic. The EMA Monograph offers a list of herbal substances, preparations, and combinations that can be used as reference material when applying for drug registration. The EMA writes a European Public Assessment Report (EPAR) for every medicine, including elderberry, that is granted marketing by the EU. It serves as a “public-friendly” overview on the medicine10 and is made available to the public.

The HMPC considers the need for review and revision of herbal medications every five years from the date of latest publication of the EPAR. This ensures that all the research and data is up to date. However, even when the information is updated, I am unclear if, absent another application, the classification is automatically upgraded to ‘well-established use’ marketing due to new studies. The last assessment report for elderberry was published in 2013. So perhaps an update is in the works this year, although I could not find any evidence of one. The EU Monograph for elderberry was updated in March 2018.

An updated assessment report (EPAR) or even just the updated European Union Monograph for elderberry is valuable to all the stakeholders who are interested in elderberry’s use in medicine. Worldwide, there have been 100+ studies on elderberry in the past five years on a range of topics. While not all of the new data is conclusive, quick and easy access to quality, timely information allows medical providers who recommend supplements to their patients, or lay people looking for useful information on medicinal products, to make more educated decisions. And for individuals or companies who may choose to develop medications further, the monograph information can facilitate their research.

Questions about quality, non-clinical, clinical, and safety concerns are addressed in the EPAR.  The EPAR (assessment report) includes:

Quality guidelines

–    Description of herbal substance, preparation, and characteristics.

–    Quality starting materials, good agricultural and collection practices

–    Quality of product combinations

–    Testing procedures and acceptance criteria for medicinal products

Non-clinical

–    Assessment of toxicity of preparations

–    Medical applications

–    Chemistry data

–    Historical data

Clinical

–    Safety and efficacy (does it work?)

–    Clinical evaluation of fixed combinations

–    Dosage

Safety

–    Available information on toxicology

–    Serious adverse events

–    Special populations (children, pregnancy, etc.)

As part of the application process, the HMPC also issues a report that reviews statements about the product that are given by the public (public comments). Absent rigorous studies about the particular herbal medicine being evaluated, it seems that the HMPC considers public consultation a valuable resource and uses it to bring to light potential benefits, or issues not addressed in the original application documents. Any concerns can then be further vetted. The comments during the 2013 application process for elderberry addressed dosing, preparation, the 30+ years of medicinal use, conditions, and also allowed for application authors to answer comments.

Conclusions

The EMA and FDA and similar governmental organizations around the world seek to protect consumers in many ways, including, requiring good clinical data for claims made about products, reviewing that data, making the data accessible to the medical and scientific communities, and regulating drugs and products marketed to the public. The strictest regulations are usually applied to newly developed drugs and tend to be less stringent for herbal substances like elderberry.

Elderberry is an active area of medical research in the EU and worldwide, and the Committee for Herbal Medicinal Products (HMPC) updated its Monograph earlier this year. But given that elderberry remains in limited use by medical professionals in the EU, I doubt elderberry will be upgraded to well-established use for marketing purposes in the EU anytime soon. Perhaps data from new studies or more ambitious studies concerning elderberry’s efficacy will spur such a change in the future. For now, elderberry will continue to be used as an over the counter supplement to remedy various ailments.