In this system, the EMA and the EDQM play core roles in the medicinal registrations and quality managements (Fig. 2). Mei Wang or Xiao-Jia Chen. The use of CHMs should be under the guidance of traditional Chinese medicine (TCM) theories. Chem Pharm Bull. The establishment of the EU quality standards and official registration for CHMs will be the first step into the EU market. 2013;28:25860. This study is partially supported by Dutch Provincie Noord_Holland MIT grant with the title and project number Oost West Telers Best (OWTB) en het projectnummer/kenmerk is: 1275358/1326082. Key steps in monitoring the quality of herbal medicinal products. The European medicinal regulatory system is based on a network of the regulatory authorities from the European Economic Area countries: the European Commission, the European Medicines Agency (EMA) and the European Directorate for the Quality of Medicines and Health Care (EDQM), making the EU regulatory system unique in the world. and other quality related issues which are under the EDQM responsibilities, such as certification of suitability to the monographs of the Ph. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Through its scientific guidelines, scientific advice programme and incentives, it facilitates research into new medicines and encourages development, thereby translating progress in medical science into medicines with real health benefits for patients. Sun MM, Wu HW, He M, Jia YS, Wang LX, Liu T, et al. Chinese medicines prevention and treatment strategy is multi-target and non-linear approach. https://www.ema.europa.eu/en/human-regulatory/herbal-medicinal-products. (2) A complex mixture of constituents extracted from plant material is present in the preparation. If you want to ask a question or request information from EMA, please Send a question to the European Medicines Agency. Therefore, in this review, the differences have been elaborated in detail by comparing the quality standards of CHMs in the EU and China. The different terms are used: Herbal drug (Ph. Therefore, their medicinal use is based on their designation or presentation. It also contains numerous monographs of medicinal drugs. Pharmacol Res. Oral toxicity of arjunolic acid on hematological, biochemical and histopathological investigations in female Sprague Dawley rats. 1). But in the ChP, different situations could be found that the two stages are normally in one continuous workflow, which integrates the two stages into one entire manufacturing process from herbal substances to finished products. MW, PFY and PYS drafted the manuscript and prepared the tables. WL prepared the figures and contributed to the critical revisions of the manuscript. .,NPUaa=G[o^ TQHFN( gNwx'xg3nkt?5ohp6 w0NZr0lM`c3o p+5SPXC5 { European Medicines Agency. Key quality factors for Chinese herbal medicines entering the EU market under management of the EQDM is a legally binding document for quality standards for medicinal products. 2013;149:45362. 2008;31(5):416-8. doi: 10.2165/00002018-200831050-00006. MIT: Mkb-innovatiestimulering Regio en Topsectoren (MIT). Their required items are generally the same, but the specific markers and limits may be different. A brief description of the procedure is available on the European Commission's website under point 3.4 of the Notice to Applicants Volume 2A - Procedures for marketing authorisation, Chapter 1 - Marketing Authorisation. 3). Eur., the Japanese Pharmacopoeia (JP), and the United States Pharmacopeia (USP)-National Formula (NF). The EDQM develops the Ph. (10th edition). Guideline | European Medicines Agency Before Thus, the DAC closes the gap in the quality and is an important source of auditing standards for drug manufacturers. With the manufacturing process of herbal medicinal products, general principles for herbal preparation e.g., water or ethanol extract, and dosage forms e.g., tablet or capsule, are rather similar in the EMA and the ChP. Careers. 2018;13:4. In existing quality standards of CHMs, quality marker usually is just one or two components or a class of substances, such as volatile oil, which is often impossible to accurately assess the quality of CHMs. Patient exposure to PAs from medicinal products should be as low as possible and must not exceed the maximum daily intake agreed by the competent authority, which is 1.0g or 0.35g according to the EMA/HMPC/328782/2016 [32]. Curr Drug Metab. Meanwhile, general quality matters are also addressed in scientific guidelines issued by the EMA such as the declaration of herbal substances (in the Ph. 2021 Jun 10;6(24):15804-15815. doi: 10.1021/acsomega.1c01201. Eur. PDF Annex 1 - World Health Organization 2). Key quality factors for Chinese herbal medicines entering the EU market. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. TCM granules are granules manufactured based on single Chinese herbal drug via extraction with heating water, separation, concentration, dry, and granulation. By using this website, you agree to our 2015;1:515. European Medicines AgencyDomenico Scarlattilaan61083 HS AmsterdamThe Netherlands. f-E.^BpMb/JxAHJ3{ Ff bDD` 5(e@ 2` $P6XTf/>I5v~@~A Ak!*S1RGGz;t*>SQ!vZFZ'Q3gMQ^ 3 Another group of toxic components is known as aristolochic acids isolated from plants of Aristolochia genus (family Aristolochiaceae) with severely nephrotoxic, mutagenic, and carcinogenic effects. Herbal medicinal products are defined as any medicinal product, exclusively containing as active ingredients one or more herbal substances, one or more herbal preparations, or a combination of the two. PMC This review mainly focuses on the key factors of quality evaluation of CHMs and explores the pathways for CHMs to enter the EU market via in-depth interpretation of the relevant requirements of laws and regulations in the EU. Eur. The following aspects should be considered in designating the extract as a herbal preparation: (1) Definition is in accordance with Directive 2001/83/EC as amended and the Ph. (4) The preparation is a mixture of related constituents reflecting the natural variability during the extraction process, but the mixture may be standardized or quantified [27]. In different pharmacopoeias, there is a huge variation in the numbers of recorded Chinese materia medica. Meanwhile, their scientific evidence, safety issues/possible toxicities and quality issues have also gained a lot of attention [16]. In the EU, there are three main regulatory pathways for bringing an herbal medicinal product to market, including traditional use registration, well-established use MA, and stand-alone full MA or mixed application for MA. The group of PAs with 1,2-unsaturated structural feature are known to have hepatotoxicity, genotoxicity, carcinogenic potential, etc. But, when placing CHMs in the EU market, the concept of DER or DER genuine needs to be used in labeling, summary of product characteristics, EU herbal monograph, etc. However, due to the lack of evidence for effective substance in many CHMs and the limitations of existing technologies, there is still no set of matching standards available. Accessed 4 Aug 2021. Chang WT, Choi YH, Van der Heijden R, Lee MS, Lin MK, Kong H, et al. The safety and efficacy of herbal medicines remain major issues of concern especially in the developing world where the use is high. Target PAs required to be tested in herbal medicinal products. European Medicines AgencyDomenico Scarlattilaan61083 HS AmsterdamThe Netherlands. Liu ZY, Li SY, Zhao WJ, Zhou G. A systematic review and meta-analysis of effect evaluation of traditional Chinese medicine in treating acute respiratory distress syndrome. (2) Extracts enriched with isolated compounds. For more information can be found underScientific guidelines. In the ChP, the limitation of aflatoxins is gradually being improved. With the development of modern sciences and technologies, the dosage forms have been greatly enriched, encompassing tablets, capsules, granules, dripping pills, inhalants and so on [5, 6]. In Europe, since 2009, Chinese herbal drug quality monographs have been gradually established and elaborated by the TCM working party in the European pharmacopoeia (Ph. In addition, TCM granules, as a special case, are elaborated separately in this review. and more will surely follow [22]. Risks associated with furocoumarins contained in preparations of Angelica archangelica L. Committee on Herbal Medicinal Products (HMPC), Send a question to the European Medicines Agency. Understanding traditional Chinese medicine therapeutics: an overview of the basics and clinical applications. For this category, it is very likely that most of CMHs are not suitable. Expert Rev Clin Pharmacol. For the mutual recognition procedure, the registration application is based on the recognition of a pre-existing national registration by the Reference Member State (RMS), and then submitted to another or more EU countries. This is a big hurdle for application for registration of Chinese herbal medicinal products in the EU when the original Chinese pharmaceutical manufacture procedure is directly used in technique dossier. Both the Ph. Yang L, Liao JB, Liu AQ, Chen X, Qu F, Cui HT, et al. 329 0 obj <>/Filter/FlateDecode/ID[<05985DACE675CB6E332094B71562C654>]/Index[313 97]/Info 312 0 R/Length 103/Prev 552712/Root 314 0 R/Size 410/Type/XRef/W[1 3 1]>>stream The site is secure. Such evaluations will add value to herbal medicines as doctors and patients will be better informed on which drugs and herbal medicines to take or not take together. Correspondence to Within the EU, the Ph. European Medicines Agency. Chin Tradit Herb Drugs. European Medicines Agency. Both pharmacopoeias also apply similar concepts for quality control or analytical methods such as macroscopic and microscopic description and thin layer chromatography (TLC) for identification, foreign matter, loss on drying, total ash, etc. Provided by the Springer Nature SharedIt content-sharing initiative. 2019 Nov 22;7:e8045. Eur., the JP and the USP-NF. Google Scholar. The authors declare that they have no competing interests. Effects of growth conditions and processing on Rehmannia glutinosa using fingerprint strategy. published scientific literature on recognised efficacy and safety. Both Chinese and European regulations and quality controls are compared. PLoS ONE. Moreover, the numbers and requirements of CHMs recorded in pharmacopoeias of other countries are significantly different from those in the ChP. Eur.) So, quality is the key point when CHMs enter the EU market. 2021 Oct 8;10(10):2691. doi: 10.3390/cells10102691. The Chinese herbal drugs required test of aflatoxins in the ChP (2020 edition). 2019;33:240920. Part 2. For improving therapeutic effects and reducing toxicity, many Chinese herbal drugs need to be processed before clinical applications [2]. Therefore, the production process of ethanol used in herbal preparations should be taken into account when considering the need for tests in the specification to control the benzene content and the frequency of testing due to benzene classified as class I solvent in the Ph. There are three main regulatory pathways for bringing a herbal medicinal product to market in EU Member States: Well-established use marketing authorisation. It is worth stating that systems biology and network pharmacology, which focuses on complex interactions in biological systems and studies drug actions and interactions with multiple targets, have the potential to be useful and important tools for systematic research of effective substances of CHMs [37, 38]. Chin Med. Herbal medicinal products. EU legislation on pharmaceutical products for human use also applies to traditional herbal medicines. Herbal drugs are the starting materials in manufacturing chain of herbal medicinal products, including Chinese herbal medicinal products.