Ir. Theo van Rooijwww.rivendell.eu

Regulatory aspects of Herbal Medicinal Products

and Supplements in EU / the Netherlands

Definitions 1 Medicinal

Categories of Herbal Medicinal Products:- Traditional Herbal Medicinal Products –

traditionele kruidengeneesmiddelen (Article 16a(1) of Directive 2001/83/EC)

2002/24/EU - Well Established Use (Article 10a of Directive 2001/83/EC )- Full registration – own data

(Article 8(3) of Directive 2001/83/EC )- Medical devices (topical + physical action)

Definitions 2 - Food Law Categories of Herbal products within Food Law:- Herbal or botanical supplements /

botanicals (in Dutch kruidenpreparaat) –Category food supplement

- Herbal teas (food) - Spices- Cosmetic products with herbal

extracts

Traditional Herbal Medicinal Products – THMP - 1

- 2004/24- Sufficient safety data and plausible

efficacy- Involves assessment of mostly

bibliographic safety and efficacy data- At least 30 years on the market, including

at least 15 years within the EU- Use without the supervision of a medical

practitioner; not administered by injection- Quality as medicinal products /

Pharmaceutical - GMP

Traditional Herbal Medicinal Products–THMP- 2

- EMA community monographs (if available) basis for registration file

- UK, Germany, Poland, Austria, Spain, have a lot of THMP registrations

- Netherlands: submission dossier to CBG (43 approvals untill end 2015)

- National - not harmonised

Well Estbalished Use – WEU- Scientific literature- well-established medicinal use within

the EU for at least ten years- with recognised efficacy and an

acceptable level of safety- Submission to: National competent

authority of a Member State for national, mutual recognition and decentralised procedures”. (CBG)

- EMA if centralised procedure applies

Granted registrations by EU member states 2004-2015

Granted registrations per EU member state until end 2015

Traditional Use: none in DK, LI, LU, MT

Well Established Use:none in CY, IT, LI, LU, MT

Germany 263 278

UK 344 1

Austria 195 51

Poland 197 24

France 23 22

Italy 10 0

Spain 90 27

Sweden 69 41

Netherlands 43 18

Amount of registrations in the EU 2004-2015

All over EU Traditonal Use Well Established Use

Registrations since 2004

1577 768

Mono preparations ± 70 % ± 80 %

Combination products

± 30 % ± 20 %

Per year average 140 90

Community Herbal monographs

- EU community herbal monographs can be found on the EMA website

- Monographs are divided into two sections:Well-established use (marketing authorisation)Traditional use (simplified registration)

Process of community monographs by HMPC / EMA

Herbal medicinal Products Committee- 1. Rapporteur: 0- 2. On going call for scientific data: 0- 3. Draft under discussion: 6- 4. Draft published:6- 5. Assessment close to finalisation =

pre-final: 6- 6. Assessment finalised: 167

Structure Community monograph - 1

- 1 NAME- 2 QUALITATIVE AND QUANTITATIVE

COMPOSITION- 3 PHARMACEUTICAL FORM - 4. CLINICAL PARTICULARS- 4.1. Therapeutic indications- 4.2. Posology and method of administration- 4.3. Contraindications- 4.4. Special warnings and precautions for use- 4.5. Interactions with other medicinal products

and other forms of interaction

Structure Community monograph - 2

- 4.6. Pregnancy and lactation- 4.7. Effects on ability to drive and use machines- 4.8. Undesirable effects- 4.9. Overdose- 5. PHARMACOLOGICAL PROPERTIES- 5.1. Pharmacodynamic properties- 5.2. Pharmacokinetic properties- 5.3. Preclinical safety data- 6. PHARMACEUTICAL PARTICULARS- 7. DATE OF COMPILATION/LAST REVISION

Approved registrations per herb in EU until end 2015 (top 10)

Traditional use Well Established

Harpagophytum 60 Ginkgo biloba 104

Pelargonium sidoides 59 Hedera helix 81

Valeriana officinalis 52 Hypericum perforatum 49

Hypericum perforatum 44 Valeriana officinalis 41

Thymus 39 Silybum marianum 31

Passiflora 37 Echinacea herba 27

Echinacea radix 25 Cimicifuga 25

Panax ginseng 25 Glycine max (lecithin) 19

Salvia officinalis 25 Pelargonium sidoides 18

Crataegus 23 Vitis vinifera 18

No harmonisation for several herbs in EU

Country Ginkgo St-Johns wort

Belgium Medicinal product + Food supplement: max 21,6 mg flavonolglycosid + 5,4 mg terpeenlacton + warning statements

Medicinal prodduct + Food supplement: max 700 μg hypericin + warning statements

Germany Only medicinal law Only medicinal law

Netherlands Medicinal + Food supplement: some warning statements indicated but not mandatory; no maximum

Medicinal + Food supplement no restrictions; warning statements by self-regulation, no maximum

Food Law- Responsibility for compliance with all

regulations regarding safety, quality, efficacy (health claims) completely by the producer / importer

- In a lot of EU countries there is an obligation to notify or authorise the product before bringing on the market

- Netherlands, UK, Austria, Sweden do not require notification / authorisation

Important aspects for herbal preparations as food supplements

1. Is the herb allowed within Food Law: mainly national situations + Novel Food Catalogue?

2. Are health claims possible?

3. Quality issues: HACCPpurity, identity, contamination

Is the herbal ingredient allowed in EU in a food supplement?

- Novel Food directives (258/97+ 2015/2283)

- EU Novel Food Catalogue: beware: not complete!

- BELFRIT list, legal value outside of Belgium low(incorporated in latest Royal Decree for plants 24-01-2017), France, Italy, but very good information

- Practice: in some EU member states a herb is a Medicinal product, in others within Food Law, with certain restrictions

Herbal ingredients food supplements – Netherlands - 1

1. NL Warenwetregeling kruidenpreparaten 2001 + additions: a. List of forbidden, unsafe herbsb. Max. toxic Pyrrolizidine Alkaloids: 1 μg per kg /liter.c. No Aristolochia acids

Herbal ingredients food supplements – Netherlands - 2

2. Proof of history of use before May 1997 (Novel Food – 258/07) in at least one EU member state – significant ?- Equivalence : extracts – bio-technology- BELFRIT – Belgian KB Plant list- practice: is it already in the market as a food supplement (a website is no proof!) and is it safe?

Is a health claim allowed?

- 1924/2006: nutrition & health claims- For botanical ingredients > 1000 dossiers

were submitted to EC/EFSA- Just a few are evaluted by EFSA: all

negative: dossier too weak, trials with patients + medical claims were rejected

- Result: all botanical claims are ON HOLD untill EC takes a final decision (end 2017?) how the evaluation by EFSA should be done: based on tradition or on science???

Requirements ON HOLD claims

- National practice per EU country can be different

- In general: Health claim is possible if:1. the claim has the same meaning as in the dossier2. Is an allowed health claim3. If the daily amount and specifications of the herb is in line with the condition of use as in the dossier(s)

Quality aspects

- Identity – Purity- ABC Adulteration program – website

ABC-Herbalgram- HACCP obligation -Import outside EU- Daily dosage, extract.- Contamination with PA (max 1 ppb:

EFSA/BfR) and PAH / 4 PAH (2015/1933: 10 / 50 ppb)

- Safety – interactions – warning statements.

Useful websites

- EFSA PA: http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/859e.pdf

- EU Novel Food Catalogue: http://ec.europa.eu/food/safety/novel_food/catalogue/search/public/index.cfm

- EMA - herbal community monographs - http://www.ema.europa.eu/ema

- ESCOP http://escop.com- ABC - American Botanical Council + magazine Herbalgram –

Adulterants program – www.herbalgram.org- AHPA – American Herbal Products Association – www.ahpa.org- Medlineplus https://medlineplus.gov/druginfo/herb_All.html

Thanks for your attention!

Questions?

Voor informatie: Ir. Theo van Rooijtheovanrooij@rivendell.eu

www.rivendell.eu