Scientific and Regulatory Basis for Development, Quality Assurance and Marketing Authorisation

Transcription

1 Scientific and Regulatory Basis for Development, Quality Assurance and Marketing Authorisation Dr. Frauke Gaedcke, Waidesch Dr. Barbara Steinhoff, Konigswinter In collaboration with Dr. Helga Blasius, Remagen With 11 colour photographs, 37 black-and-white figures and 30 tables Scientific Publishers StUttgart 2003 CRC PRESS Boca Raton London New York Washington, DC.

2 Preface V Abbreviations.. XIII 1 Definitions Phytotherapy Herbal medicinal products Herbal drugs Herbal drug preparations Herbal extracts Classification of extracts in terms of their physical state Native and not-native extracts (extract preparations) Adjusted (standardised), quantified and "other" extracts Preparations of fresh plants Ratio of the herbal drug to the extraction solvent Ratio of the herbal drug to the native herbal drug preparation (native extract) (DER native ) Definition of the DER native Calculation of the DER native Calculation of the daily dose (DD) of the herbal drug preparation via the DER native Ratio of the herbal drug to the herbal extract preparation Factors influencing the quantity of native herbal drug preparation (native extract) and the DER native What is meant by standardisation? Measures designed to ensure consistency of a herbal extract Adjustment of a herbal drug preparation to a defined range of therapeutically active constituent(s) Adjustment of a herbal drug preparation to a fixed content of more than one therapeutically active constituent (so-called "double-adjustment").. 19

3 1.12 Classification of plant constituents and extracts Constituents with known therapeutic activity (therapeutically active constituents) Constituents which contribute to therapeutic efficacy (active constituents) Marker substances Standardised extracts Quantified extracts Other extracts Refined ("purified", "enriched") extracts Mixed extracts (extracts of mixtures of herbal drugs, one-pot extracts) Mixtures of herbal extracts (multiple-pot extracts) 28 2 Labelling of herbal drug preparations (extracts) Adjusted (standardised) extracts (siccum extracts) Quantified extracts (siccum extracts) Other extracts Liquid extracts (fluida) Tinctures Soft extracts 34 3 Quality assurance of herbal medicinal products General aspects Quality assurance of the herbal starting material Identification test Assay Purity tests Reference substances Quality assurance of the herbal extract Extraction solvent Extraction procedure Evaporation Microbial decontamination Drying Filing of the specification Quality assurance of the finished herbal medicinal product Development pharmaceutics 59

4 3.4.2 Disintegration time Release of herbal medicinal products 63 4 Can herbal extracts and herbal medicinal products be "essentially similar"? Different approaches for the definition of phytoequivalence Phytoequivalence and pharmaceutical equivalence Criteria for pharmaceutical equivalence Herbal starting material Type and concentration of extraction solvent Manufacturing procedure Conformity of batches and extracts Dosage form and dosage How to establish therapeutical equivalence 76 5 The European marketing authorisation system si 5.1 Directives relating to medicinal products The centralised, decentralised and national procedure The option of bibliographic applications Application of the decentralised procedure to herbal medicinal products The Herbal Medicinal Products Working Party (HMPWP) The future of marketing authorisation in the EU 88 6 Legal provisions relating to the quality of herbal drugs, herbal drug preparations and herbal medicinal products Quality, efficacy and safety as prerequisites for marketing authorisation The European Pharmacopoeia Annex of Directive 2001/83/EC Qualitative and quantitative particulars of the constituents Development pharmaceutics Description of the method of preparation Control of starting materials Control tests in intermediate stages 98 IX

5 6.3.6 Control tests for the finished product Stability tests The European Guidelines "Quality of herbal medicinal products" and "Specifications" Other European and international guidelines Tests for special impurities Microbiological testing Heavy metals Aflatoxins Plant protection products Ethylene oxide Ill Radioactivity Residual solvents Filing of the documentation: Notice to Applicants Bioavailability Legal provisions relating to efficacy and safety of herbal medicinal products 7.1 Evidence of efficacy and safety required for herbal medicinal products including the well-established medicinal use Attempts to harmonise the assessment criteria Special requirements for fixed combinations Marketing authorisation of "traditionally used" herbal medicinal products: the national ways and future European options Research in phytotherapy 129 in 8 Herbal Medicinal Products Worldwide The WHO Traditional Medicine Programme WHO Guidelines for the assessment of herbal medicines Model monographs of widely used medicinal plants Further WHO activities 132

6 Annex I II CPMP/CVMP Note for Guidance on Quality of Herbal Medicinal Products 135 General monographs on herbal drugs, herbal drug preparations and herbal teas (Ph. Eur., Suppl. 2000) 142 III General monograph on extracts (Ph. Eur. 2002, Suppl. 4.3) 145 IV V Monographs on herbal drugs and herbal drug preparations published in the Ph. Eur. 2002, including Suppl. 4.1 to Monographs and component characteristics published by the German Commission E 151 VI Monographs published by ESCOP (fascicules 1-6) 166 VII WHO Model Monographs of Widely used Medicinal Plants (including Vol. I, II and III). 170 VIII WHO Publications relating to herbal medicines 171 Index 173 XI