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Homeopathic medicinal products: medicinal aspects
Overview
Proof of the specific homeopathic efficacy
• Proof of the specific homeopathic efficacy
• Background: - Dir. 2001/83 EC as amended: Marketing authorizations for medicinal products only when clinical efficacy is proven - National exemptions for homeopathic medicinal products in AT:
• Justification of homeopathic use • Safety assessment • Homeopathic drug proving
Arzneimittelgesetz (current version) §9b: no clinical data necessary, but data on specific homeopathic efficacy Bibliographic proof Correlation homeopathic active substance – indication o No exemptions regarding safety Assessment according to current scientific knowledge
• Special aspects for SmPC, PIL
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Reinhard Länger Expert Group Herbal Medicinal Products & Homeopathics Department Quality Assessment of Medicinal Products AGES-Gespräch „Homeopathics: an Update“ Vienna, 12.5.2015 www.basg.gv.at
Österreichische Agentur für Gesundheit und Ernährungssicherheit GmbH
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Proof of the specific homeopathic efficacy
Justification of homeopathic use
Justification of homeopathic use
• Standard references:
• Necessary for registrations according to AMG §11
• Justification for stocks which are not included:
- Monographs German commission D o
- References needed
• HMA-HMPWG:
Comments in: Keller-Greiner-Stockebrand: Homöopathische Arzneimittel, Materialien zur Bewertung
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• Additional references? - No official list of acceptable references - Case-by-case decision
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01About_HMA/Working_Groups/HMPWG/2012_06_HMPWGPointsConsiderJustificationUs e.pdf
- List entries of stocks for which hompeopathic use is justified (2 lists)
Coherence of the information in several references o Number of references containing identical information o ….
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http://www.hma.eu/fileadmin/dateien/Human_Medicines/01About_HMA/Working_Groups/HMPWG/2013_09_HMPWG_First_list_entries.pdf http://www.hma.eu/fileadmin/dateien/Human_Medicines/01About_HMA/Working_Groups/HMPWG/2015_03_HMPWG_Second_list_entries.pdf
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• Registration for new stocks? - Registration not possible, only marketing authorization! - Homeopathic drug proving necessary - Clear link to new established indication necessary
• Information from websites, popular books or
journals, single references not sufficient 4
Also references acceptable which do not include an indication, e.g. monographs in pharmacopoeias Materiae medicae, publications of homeopathic drug provings o Classical homeopathic texts and documented homeopathic traditions, recent publications, … o Quality of references: Information from websites, popular books or journals, single references not sufficient o
- Points to consider on the justification of homeopathic use of the stock
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Safety assessment
Safety assessment
Homeopathic drug proving
• HMA-HMPWG:
• Safety assessment follows the general principles for
• For all homeopathic drug provings:
medicinal products
- Points to consider on the non-clinical safety of homeopathic medicinal products of botanical, mineral and chemical origin o
Calculations starting with TTC (threshold of toxicological concern), PDE (permitted daily exposure) or LHRD (lowest human recommended dose) o Historical lists no longer state of the art o Currently on HMPWG website only comments from public consultation on a first trial of assessment published o
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01About_HMA/Working_Groups/HMPWG/2007_07_biological_safety_ bmco.pdf
- Points to consider on the safety of homeopathic medicinal products of biological origin o
- Sufficient number of subjects - Statistical evaluation - Trials follow GCP, principles of ICH-E6
- First safe dilution:
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01About_HMA/Working_Groups/HMPWG/2007_07_safety_MP_BO.pdf
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• Proving to enlarge or to specify more precisely the
proving symptoms of an already known homeopathic substance - 1 trial could be sufficient
- Safety in case of stocks from biological origin Viral safety, microbiological risk o Risk of transmission of TSE o General guidelines for medicinal products apply (e.g. use of bovine serum, human somatic cell therapy, use of genetically modified organisms) o
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• Proving to introduce a new substance into the
homeopathic materia medica - At least 2 trials necessary in order to confirm results 9
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Homeopathic drug proving
Homeopathic drug proving
SmPC, PIL: Nomenclature
• Guidance documents
• Homeopathic drug proving = clinical trial
• Nomenclature following Pharmacopoeia
- BfArM o
- In case of questions:
Recommendations of the commission D regarding planning and realization of drug provings (1998)
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http://www.bfarm.de/SharedDocs/Bekanntmachungen/DE/Arzneimitt el/besTherap/bm-besTherap-19981118-zul-hompdf.pdf?__blob=publicationFile&v=3
- + synonyms (old homeopathic names)
Check BASG website: medicines – prior to authorization – clinical trials
- Old names can be mentioned in the product information (in brackets)
http://www.basg.gv.at/en/medicines/prior-to-authorisation/clinicaltrials/ o
Contact:
[email protected]
- European Committee for Homeopathy o
Homeopathic drug proving guidelines (2011) http://www.homeopathyeurope.org/publications/guidelines/homeopat hic-provings-archive/ECH_Proving_Guidelines_2004_v1.pdf/view
- European Council for Classical Homeopathy o
- All other parts of the dossier, application form: official name
ECCH Guidelines for homeopathic provings (2009) http://www.homeopathyecch.org/images/stories/pdf/ecch%20guidelines%20for%20provings. pdf
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SmPC, PIL: Excipients with known effects
SmPC, PIL: Excipients with known effects
SmPC, PIL: Standard sentences
• Relevant guideline:
• Lactose:
• Indication: - PIL only:
- Notice to applicants, Vol. 3B, Excipients in the label and package leaflet of medicinal products for human use
(selected parts)
- Special wording AT: o
• Ethanol:
Daily dose