EMA Publishes Final Guidelines on Quality and Specifications for HMPs

As previously announced, the European Medicines Agency (EMA) published the final guidelines (Revision 3) on quality and specifications for herbal medicinal products (HMPs). Amongst others, a written GACP confirmation for the herbal substance should be provided. In addition, EMA´s HMPC recently published a concept paper on the revision of the GACP guideline. The deadline for comments is 1 June 2022.

Written GACP confirmation for the Herbal Substance

The Quality Guideline contains under section 5.1.1. Control of herbal substances the following provisions (amongst others):

• A comprehensive specification for each herbal substance must be submitted.
• Information on the site of cultivation / collection, the time of harvesting and stages of growth, treatment during growth with pesticides etc., and drying and storage conditions should be included.
• The origin should be stated at least on country level.
• An adequate quality assurance (QA) system for the collection and / or cultivation, harvest and primary processing according to GACP.
• A written GACP confirmation (the draft version for Revision 3 used the wording "written GACP declaration") should be provided by the herbal substance supplier, the manufacturer of the active substance or the HMP, as appropriate.
• If a monograph for a herbal substance exists in the European Pharmacopoeia (Ph. Eur.) the herbal substance should be in accordance with this monograph.

In general, herbal substances must be tested, unless otherwise justified, for microbiological quality, mycotoxins (aflatoxins, ochratoxin A), pesticide residues and fumigation agents, heavy metals and likely contaminants (including heavy metals not mentioned in the  Ph. Eur. monograph “Herbal drugs” and contaminants present in the specific environment), foreign matter and adulterants, etc.

Herbal Medicinal Products (HMPs)

The tests on the final medicinal product should include (amongst others):

• The qualitative and quantitative determination of active substances.
• The characteristic properties of the dosage form and the entire finished product, including packaging, and medical devices used for the application of the product (e.g. vaporizers).
• Chromatographic fingerprinting.
• The criteria provided in the Ph. Eur. chapters 5.1.4 / 5.1.8 (depending on the dosage form / route of administration) for microbiological quality (unless otherwise justified).

Interestingly, for elemental impurities, the principles of ICH Q3D should be applied for the final HMP (HMPs are usually out of scope of ICH Q3D). It is the responsibility of the applicant to justify at which stage testing of impurities takes place (i.e. herbal drug, herbal drug preparation (e.g. extract), final HMP). In any case, the chosen acceptance criteria should be justified and the controls to be applied should take into account current intake limits and dosage of the HMP.

More detailed information is provided in the EMA Guidelines on quality of herbal medicinal products/traditional herbal medicinal products and on specifications: test procedures and acceptance criteria for herbal substances, herbal preparations and herbal medicinal products/traditional herbal medicinal products.