Herbal Medicines: Traditinal Herbal Registratin In the UK, cmpanies can nly sell herbal medicines with the apprpriate prduct licence, as fllws: A full marketing authrisatin based n the safety, quality and efficacy f the herbal prduct; r A traditinal herbal registratin based n the safety, quality and evidence f traditinal use f the herbal prduct. In this article, Dr Rsanna Cper explres traditinal herbal medicines and traditinal herbal registratins. Herbal Prducts Are they Medicines, Fd r Csmetics? Herbal prducts can be classified as medicines, fd r csmetics. The key is t assess yur herbal prducts t ensure that they are crrectly classified and therefre cmpliant under the law. Traditinal Herbal Medicinal Prducts Article 1 f Directive 2001/83/EC (as amended) defines a traditinal herbal medicinal prduct as a herbal medicinal prduct that fulfils the cnditins laid dwn in Article 16a(1). The cnditins laid dwn in Article 16a(1) are as fllws: 1. A simplified registratin prcedure (hereinafter traditinal- use registratin ) is hereby established fr herbal medicinal prducts which fulfil all f the fllwing criteria: (a) they have indicatins exclusively apprpriate t traditinal herbal medicinal prducts which, by virtue f their cmpsitin and purpse, are intended and designed fr use withut the supervisin f a medical practitiner fr diagnstic purpses r fr prescriptin r mnitring f treatment; (b) they are exclusively fr administratin in accrdance with a specified strength and pslgy; (c) they are an ral, external and/r inhalatin preparatin; (d) the perid f traditinal use as laid dwn in Article 16c(1)(c) has elapsed; (e) the data n the traditinal use f the medicinal prduct are sufficient; in particular the prduct prves nt t be harmful in the specified cnditins f 1 P a g e
use and the pharmaclgical effects r efficacy f the medicinal prduct are plausible n the basis f lng-standing use and experience. A herbal medicinal prduct is defined in Article 1 f Directive 2001/83/EC (as amended) as any medicinal prduct, exclusively cntaining as active ingredients ne r mre herbal substances r ne r mre herbal preparatins, r ne r mre such herbal substances in cmbinatin with ne r mre such herbal preparatins. Herbal substances are defined as all mainly whle, fragmented r cut plants, plant parts, algae, fungi, lichen in an unprcessed, usually dried, frm, but smetimes fresh. Certain exudates that have nt been subjected t a specific treatment are als cnsidered t be herbal substances. Herbal substances are precisely defined by the plant part used and the btanical name accrding t the binmial system (genus, species, variety and authr). Traditinal Herbal Registratin A Traditinal Herbal Registratin is available, rather than a Marketing Authrisatin, fr placing traditinal herbal medicinal prducts n the market r fr their distributin by way f whlesale dealing in the UK. Under Directive 2004/24/EC: Recital 4 - Having regard t the particular characteristics f these medicinal prducts, especially their lng traditin, it is desirable t prvide a special, simplified registratin prcedure fr certain traditinal medicinal prducts. Hwever, this simplified prcedure shuld be used nly where n marketing authrisatin can be btained pursuant t Directive 2001/83/EC, in particular because f a lack f sufficient scientific literature demnstrating a wellestablished medicinal use with recgnised efficacy and an acceptable level f safety. It shuld likewise nt apply t hmepathic medicinal prducts eligible fr marketing authrisatin r fr registratin under Directive 2001/83/EC. (5) The lng traditin f the medicinal prduct makes it pssible t reduce the need fr clinical trials, in s far as the efficacy f the medicinal prduct is plausible n the basis f lng-standing use and experience. Pre-clinical tests d nt seem necessary, where the medicinal prduct n the basis f the infrmatin n its traditinal use prves nt t be harmful in specified cnditins f use. Hwever, even a lng traditin des nt exclude the pssibility that there may be cncerns with regard t the prduct's safety, and therefre the cmpetent authrities shuld be entitled t ask fr all data necessary fr assessing the safety. The quality aspect f the medicinal prduct is independent f its traditinal use s that n dergatin shuld be made with regard t the necessary physic-chemical, bilgical and micrbilgical tests. Prducts shuld cmply with quality standards in relevant Eurpean Pharmacpeia mngraphs r thse in the pharmacpeia f a Member State. 2 P a g e
(6) The vast majrity f medicinal prducts with a sufficiently lng and cherent traditin are based n herbal substances. It therefre seems apprpriate t limit the scpe f the simplified registratin in a first step t traditinal herbal medicinal prducts. (7) The simplified registratin shuld be acceptable nly where the herbal medicinal prduct may rely n a sufficiently lng medicinal use in the Cmmunity. Medicinal use utside the Cmmunity shuld be taken int accunt nly if the medicinal prduct has been used within the Cmmunity fr a certain time. Where there is limited evidence f use within the Cmmunity, it is necessary t assess carefully the validity and relevance f use utside the Cmmunity. (8) With the bjective f further facilitating the registratin f certain traditinal herbal medicinal prducts and f further enhancing harmnisatin, there shuld be the pssibility f establishing a Cmmunity list f herbal substances that fulfill certain criteria, such as having been in medicinal use fr a sufficiently lng time, and hence are cnsidered nt t be harmful under nrmal cnditins f use. Recital 4 f Directive 2004/24/EC prvides that the simplified prcedure f Traditinal Herbal Registratin is nly available where n marketing authrisatin can be btained fr the prduct (pursuant t Directive 2001/83/EC) because f a lack f sufficient scientific literature demnstrating a well-established medicinal use with recgnised efficacy and an acceptable level f safety. Marketing Authrisatin There is a general requirement under Article 6(1) f Directive 2001/83/EC (as amended), that a medicinal prduct must have a Marketing Authrisatin befre it can be placed n the market f a Member State, r be distributed by way f whlesale dealing in the UK. N medicinal prduct may be placed n the market f a Member State unless a marketing authrizatin has been issued by the cmpetent authrities f that Member State in accrdance with this Directive Fr the purpses f this Directive, a medicinal prduct relates t substances (r cmbinatin f substances) which are presented as being capable f preventing disease in human beings r having an effect n the physilgical functins f human beings (Article 1 f Directive 2001/83/EC (as amended)). Medicinal prduct: (a) Any substance r cmbinatin f substances presented as having prperties fr treating r preventing disease in human beings; r (b) Any substance r cmbinatin f substances which may be used in r administered t human beings either with a view t restring, crrecting r 3 P a g e
mdifying physilgical functins by exerting a pharmaclgical, immunlgical r metablic actin, r t making a medical diagnsis. Applicatins fr marketing authrisatin f a herbal medicinal prduct must be accmpanied by extensive supprting data, including results f physic-chemical, bilgical r micrbilgical tests, pharmaclgical tests, txiclgical tests and clinical trials, in rder t prve its safety, quality and efficacy. Where yu can prve that there is sufficient scientific literature t demnstrate a wellestablished medicinal use with recgnised efficacy and an acceptable level f safety, then yu may nt be required t prvide the results f pre-clinical tests r clinical trials. The Directive 2004/24/EC states that where the cmpetent authrities judge that a medicine fulfils the criteria fr a Marketing Authrisatin, they shuld nt grant a Traditinal Herbal Registratin (Article 16a(3) Directive 2001/83). in cases where the cmpetent authrities judge that a traditinal herbal medicinal prduct fulfills the criteria fr authrisatin in accrdance with Article 6 the prvisins f this chapter shall nt apply. Use fr 15 years within the Cmmunity Evidence must be prduced t the Medicines and Healthcare Prducts Regulatry Agency ( MHRA ) t shw that a traditinal herbal medicinal prduct, r a crrespnding prduct, has been in medicinal use thrughut a 30 year perid preceding the date f applicatin, including at least 15 years within the Cmmunity (Article 16c(1)(c) f Directive 2001/83/EC (as amended)). (c) bibligraphical r expert evidence t the effect that the medicinal prduct in questin, r a crrespnding prduct has been in medicinal use thrughut a perid f at least 30 years preceding the date f the applicatin, including at least 15 years within the Cmmunity. At the request f the Member State where the applicatin fr traditinal-use registratin has been submitted, the Cmmittee fr Herbal Medicinal Prducts shall draw up an pinin n the adequacy f the evidence f the lng-standing use f the prduct, r f the crrespnding prduct. The Member State shall submit relevant dcumentatin supprting the referral; Article 16c(2) Directive 2001/83/EC (as amended) describes a crrespnding prduct as A crrespnding prduct, as referred t in paragraph 1(c), is characterised by having the same active ingredients, irrespective f the excipients used, the same r similar intended purpse, equivalent strength and pslgy and the same r similar rute f administratin as the medicinal prduct applied fr. Qualified Persn 4 P a g e
Any manufacturer hlding a traditinal herbal registratin and manufacturing a traditinal herbal medicinal prduct r a medicinal herbal prduct under a marketing authrisatin must hld a manufacturer s/imprter s authrisatin ( MIA ). Under Eurpean legislatin, the services f at least ne qualified persn must be permanently and cntinuusly at the dispsal f the hlder f a MIA, wh wuld take respnsibility fr the quality f the prducts manufactured at the site where manufactured. The qualified persn must be named n the MIA. The qualified persn des nt have t be a full time emplyee; he r she culd be a cntractr. The main pint is t have a technical agreement between the manufacturer and the qualified persn setting ut the cntractual respnsibilities f the qualified persn. The duties f a qualified persn include: Gd Manufacturing Practice ( GMP ) are fllwed; Adhering t the terms f the traditinal herbal registratin r the marketing authrisatin; Ensuring validatin f manufacturing and testing prcesses; All necessary quality cntrl checks and tests have been cnducted; Ensuring all imprted prducts meet the legal requirements; Ensuring the testing f all prducts imprted frm utside the Eurpean Ecnmic Area ( EEA ) are tested within the EEA t meet the requirements f traditinal herbal registratin r the marketing authrisatin; Each batch is certified/recrded that the requirements f traditinal herbal registratin r the marketing authrisatin are met; Maintaining recrd and ensuring entries are recrded as sn as practicable after each batch has been manufactured and befre the batch is released fr sale. A qualified persn must be resident within the UK. Respnsible Persn The hlder f a whlesale dealer s licence must have a respnsible persn in accrdance with Article 79(b) f Directive 2001/83/EC (as amended). The 5 P a g e
Respnsible persn is respnsible fr safeguarding prducts against ptential hazards arising frm pr distributin practice. The respnsible persn is respnsible fr the fllwing: T safeguard prduct users against ptential hazards arising frm pr distributin practices; T ensure that the cnditins f the whlesale dealer s licence are met; Cmpliance with the guidelines f Gd Distributin Practice. A respnsible persn must be resident within the UK. MHRA Guidelines Accrding t the MHRA Guidelines, fr sme herbal medicines there is sufficient evidence in the public dmain fr an applicant t be able t btain a Marketing Authrisatin under the prvisins fr prducts cntaining active substances with 'well established' use by referring t apprpriate scientific literature. Where this is the case the MHRA will nt grant a traditinal use applicatin but will instead ask the applicant t apply fr a Marketing Authrisatin. Based n the MHRA's experience it is likely that this wuld apply in nly a minrity f cases. The MHRA will nt take the view that a prduct ught t fllw the 'well established' rute t a Marketing Authrisatin simply because the medicine cntains a particular herbal ingredient. It may well be that there are sme herbal medicines that have several accepted indicatins, f which ne might be apprpriate fr a Marketing Authrisatin under the 'well established use' prvisins while anther is suitable fr traditinal use registratin. Likewise, it may be that the 'well established use' prvisins are applicable t a range f prducts that use a particular herbal ingredient. Hwever, traditinal use might be applicable where that ingredient is used in cmbinatin with ther active herbal ingredients, particularly fr ther therapeutic indicatins. Such cmbinatins wuld need t satisfy the requirements fr traditinal use registratin including that the efficacy is plausible - based n lng use and experience. There have been sme differences f interpretatin f the 'well established' prvisins between regulatry authrities in different EU Member States. Advice given in ther EU Member States will nt necessarily be applicable in the UK and vice versa. Ptential Grunds fr Revcatin f a Traditinal Herbal Registratin The fllwing are ptential grunds upn which Cmpany A may challenge the traditinal herbal registratin fr certain prducts f Cmpany B. Supprting evidence wuld be required t substantiate the assertins by Cmpany A. 6 P a g e
The prducts that have been granted a traditinal herbal registratin, are nt traditinal herbal medicinal prducts and the traditinal herbal registratin f Cmpany B ught t be revked n the fllwing grunds:- The prducts upn which Cmpany B has based its applicatin fr the traditinal herbal registratin, were develped as part f a pharmaceutical prcess using herbal ingredients; Only Cmpany A wns the rights t the prcess (knw-hw); The prduct wned by Cmpany A with identical/similar cmpsitin t the prducts wned by Cmpany B has been n sale in Eurpe fr less than 15 years; There is a questin mark ver the safety f the prducts wned by Cmpany B; The prducts wned by Cmpany B require a Marketing Authrisatin in rder fr Cmpany B t sell these prducts in the UK and the rest f the Eurpean Unin; Marketing Authrisatins already exist fr an identical (if nt, similar) prduct wned by Cmpany A. What is a brderline prduct? Article 1 f Directive 2001/83/EC (as amended) as amended defines a medicinal prduct as: Any substance r cmbinatin f substances presented as having prperties fr treating r preventing disease in human beings; Any substance r cmbinatin f substances which may be used in r administered t human beings either with a view t restring, crrecting r mdifying physilgical functins by exerting a pharmaclgical, immunlgical r metablic actin, r t making a medical diagnsis. There are sme prducts where it is nt s easy t distinguish a medicine frm, fr example, csmetics r fd supplements. These are knwn as brderline prducts. A prduct which is fr use nly as a tiletry, disinfectant, fd r beverage is nt nrmally regarded as a medicinal prduct, and wuld nt require a marketing authrisatin t be sld in the UK. Dietary supplements cntaining vitamins, amin acids r minerals, are generally subject t fd safety and fd labelling legislatin rather than medicines cntrl. 7 P a g e
In the event that a fd and/r csmetic cntain a pharmaclgically active substance r make medicinal claims (claims t treat r prevent disease, r t interfere with the nrmal peratin f a physilgical functin f the human bdy are regarded as medicinal). Cnclusin Cmpanies manufacturing and/r distributing herbal medicines must ensure cmpliance with the law. RT COOPERS, 2013. This Briefing Nte des nt prvide a cmprehensive r cmplete statement f the law relating t the issues discussed nr des it cnstitute legal advice. It is intended nly t highlight general issues. Specialist legal advice shuld always be sught in relatin t particular circumstances. The authr is Dr Rsanna Cper f RT Cpers Slicitrs. She is an expert in regulatry law, in particular, herbal medicines. Dr Cper is a chartered chemist and a fellw f the Ryal Sciety f Chemistry. She may be cntacted n +44 (0) 207 488 9947 r by email: enquiries@rtcpersslicitrs.cm. Fr mre infrmatin n the services prvided by RT Cpers n csmetic law, visit http://www.rtcpers.cm/practice_regulatry.php. 8 P a g e