Finzelberg s role in developing Successful herbal medicinal products

Transcription

1

2 Finzelberg s role in developing Successful herbal medicinal products From plants to modern herbals Active Phytopharmaceutical Ingredients Pharma Asia 2017, Dr. Rainer Kunz 1

3 Welcome to the nature network 2

4 Raw Material Extract as API Herbal Medicinal Product Regulatory Affairs Markets and Products Summary 3

5 Welcome to the nature network the nature network is the umbrella for the three business divisions Martin Bauer Group B2B Europlant Group B2C PhytoLab Employees More than 3,000 worldwide Headquarter of MB-Holding Germany TO > 500 Mio 4

6 Welcome to Finzelberg Finzelberg is a member of the Martin Bauer Group Founded 1875 by pharmacist Hermann Finzelberg Employees 2017 > 300 Product Portfolio Extracts from more than 100 different plants Turnover 2017 >70 Mio 5

7 Welcome to Finzelberg Active phytopharmaceutical ingredients paired with regulatory support Functional ingredients & concepts ready to use for food supplements 6

8 How can we guarantee Safety, Efficiency and Quality of herbal medicinal products? Value creation chain with highest traceability and sustainability 7

9 Raw Material Extract Herbal Medicinal Product Registration Process Marketing 8

10 Introduction The nature network Raw Material Extract as Active Ingredient Herbal Medicinal Product Regulatory Affairs Markets and Products Summary 9

11 Raw Material Quality right from the start 10

12 Quality of the raw material Challenges Matrix of a plant is a very complex multi-component system. Matrix of a plant itself differs from region, year of harvesting, period of harvesting, plant species, cultivation, wild collection As a consequence the material = drug differs in quality from season to season, from location to location,... Plants are exposed to external impurities (e.g. pesticides, heavy metals, microorganism, aflatoxins, etc.) 11

13 Quality of the raw material EMEA guidelines Guideline on Good Agriculture and Collecting Practice EMEA / HMPC / /2005 (GACP) covers the following: Quality assurance Personnel and education Building and facilities Equipment Documentation Cultivation Collection Harvest Primary processing Packaging Storage and distribution 12

14 Influence on a positive development Improvements of the drying process Traditional Drying areas Drying areas after upgrade 14

15 Influence on a positive development Improvements of the storage Raw Material without GMP Raw Material with GMP 15

16 the nature network the nature network is the umbrella for Martin Bauer Group, PhytoLab, Europlant Group. 99 % raw material supply to Finzelberg with 100 % traceability! the nature network 16 16

17 Introduction The nature network Raw Material Extract as Active Ingredient Herbal Medicinal Product Regulatory Affairs Markets and Products Summary 17

18 The production process The following production types are predominantly used at Finzelberg Maceration (tea-type) Percolation (espresso-type) perkolator 4 perkolator 3 perkolator C perkolator 1 herb / solvent ratio =1:6-1:35 More sophisticated production types are used at Finzelberg as well: Counter current extraction Liquid-liquid extraction 18

19 Extraction solvents The following solvents are commonly used at Finzelberg water ethanol methanol acetone ethyl acetate 19

20 Extract development - Influence of solvent on API TLC of Valerenic acids (DAB 1999) TLC of volatile oil (Finzelberg) VS = Valerenic acid OH-VS = Hydroxyvalerenic acid 20

21 Drying Process The right choice The following types of dryers are the most common in industry, all of them are available at Finzelberg. Spray tower dryer Vacuum belt dryer Spray belt dryer Shovel dryer. 21

22 Finzelberg was the first plant extracts producer to gain GMP certification in 2005 HACCP certification since 2009 Fulfils the premises both for the pharmaceutical and nutraceutical requirements 22

23 Quality standards within the nature network DIN EN ISO 9001: 2008 Permission to manufacture pharmaceutical goods according to German law: 13 AMG GMP Certificate Hygienic Certificate IFS (International Food Standard): Hygiene & HACCP Laboratory Admission according to ISO 17025, 93/99/EWG,GLP Biological products (EC) No. 834/2007, (EC) No. 889/2008 NOP (National Organic Program, USDA/NOP-Final Rule) Kosher/Halal FDA inspected the nature network

24 Introduction The nature network Raw Material Extract as Active Ingredient Herbal Medicinal Product Regulatory Affairs Markets and Products Summary 24

25 The Herbal Medicinal Product A. Selection of the herbal drug / extract / combination as the active pharmaceutical ingredient Finzelberg portfolio > 100 drugs, supplying worldwide Phyto Blockbusters since decades - Can be taken form standard portfolio - Can be developed to the needs of the client / market - tailor made 25

26 The Herbal Medicinal Product B. Definition of the formulation - Definition of the application for the finished product solid / liquid / thin film etc.etc.: Finzelberg has long tradition in searching for best dosage forms and can offer and develop appropriate extract formulas. - Galenics: partnership with CMO s in main markets leads to quick development of FDF s (Brasil, Germany, Pakistan) 26

27 The Herbal Medicinal Product C. Quality Management - Methods of analysis: Either already existing from Monographs, can be completely new developed by Finzelberg or partner s of the nature network - Dissolution tests, AMES tests, Contaminants! Etc., toxicological testing - Product stability both for API and finished product can be done by Finzeleberg or internal and external partners 27

28 the nature network the nature network is the umbrella for Martin Bauer Group, PhytoLab, Europlant Group. the nature network 28 28

29 Introduction The nature network Raw Material Extract as Active Ingredient Herbal Medicinal Product Regulatory Affairs Markets and Products Summary 29

30 The Phyto - Dossier in Europe Every registered medicinal herbal product in Europe needs a Dossier. In the early past a common format has been established also known as Common Technical Document (CTD) The CTD file is an agreement to assemble all aspects on quality, safety and efficacy in a common format The CTD file has led to a harmonized structure The structure of the CTD file is strictly defined 30

31 The Dossier CTD triangle Organized into five modules 1 st module is region specific Modules 2, 3, 4, 5 are common for all regions Monographs and clinical studies 31

32 Module 3 - Quality of active substance Table of content 3.2.S 3.2.S S S S S S S S S S S S S S.3.2 Raw Material General Information Nomenclature Structure General Properties Manufacture (Production) Manufacturer(s) Description of manufacturing process and process controls Control of materials Controls of critical steps and intermediates Process validation and/or evaluation Manufacturing process development Characterisation Elucidation of structure and other characteristics Impurities 32

33 Module 3 - Quality of active substance Table of content 3.2.S S S S S S S S S S S S.7.3 Control of drug substance Specification Analytical Procedures Validation of analytical procedures Batch analyses Justification of Specification Reference Standards or Materials -- from Phytolab Container Closure System Stability -- by Phytolab or Finzelberg Stability summary and conclusions Post-approval stability protocol and stability commitment Stability data 33

34 Module 3 - Quality of active substance 3.2.P 3.2.P P P P P P P P P P P P P P P P P P P P P P P P P.8 DRUG PRODUCT Description and composition of the drug product Pharmaceutical development Manufacture Manufacturer(s) Batch formula Description of manufacturing process and process controls Controls of critical steps and intermediates Process validation and / or evaluation Control of excipients Specifications Analytical procedures Validation of analytical procedures Justification of specifications Excipients of human or animal origin Novel excipients Control of drug product Specification(s) Analytical procedures Validation of analytical procedures Batch analyses Characterisation of impurities Justification of specifications Reference standards or materials Container closure system Stability Worldwide partnerships with CMO s and partners allow fast development and rapid market access! 34

35 Introduction The nature network Raw Material Extract as Active Ingredient Herbal Medicinal Product Regulatory Affairs Markets and Products Summary 35

36 Classification of finished herbal products a challenge for regulatory affairs departments! Medical Devices Food Novel Food Food supplements Dietary supplements Herbal Medicinal Products Pharma Cosmetics 36

37 Product focus Herbal Medicinal Products Legal regulations & defined rules for access to market & sales Transparent situation for the evaluation of necessary investment Long life-cycle of product 37

38 Estimated size of herbal markets worldwide in TO (2017) Total world market for herbals of all types estimated 100 Bilion USA??? Europe 4 Bilion Asia??? Germany 1,2 Bilion 38

39 German Herbal Pharmacie market facts % of TO in Germany are generated by 30 companies, the Top Ten alone 600 Mio! 75 % of german population is using herbal based products with increasing tendency! Number of people taking natural products more than doubled from 1970 to 2010 from 15 % to 35 %! Complemetary medication increasing > 60 % would use a natural product alone or in combination in case of illness As preventive medication 40 % of germans are taking natural products. 39

40 German Herbal Pharmacie market 2016 facts Main indications Mio. Euro Cough and cold 480 Urologica 60 Gastrointestinal 144 Calm and Sleep 72 Muscle and articulation problems 36 Percutane applications and inhalations 48 Others 252 In 2004 withdrawal of reembursement! Nevertheless after transition phase recovered stable OTC market Total 1,200 Source: IMS Health 40

41 Some famous registered herbal medicinal products in the german pharmacy market 41

42 Cough and Cold herbal Bestsellers Sinupret (Herbal mixture) > 50 Mio Umckaloabo (Pelargonium root) > 20 Mio Prospan (Ivy leaf) >> 10 Mio Silomat (Althaea Root) from Boehringer / Sanofi Bronchicum >> 10 Mio Plerus (Pelargonium root) Saudi Arabia 42

43 Cough and Cold drug Bestsellers and Trends Primrose Thyme Ivy Pelargonium Plantaginis Lanceolata Marshmallow 43

44 Calm and sleep bestsellers 2017 Baldriparan stark + Beruhigung (Pfizer): >> 10 Mio Valerian Melissa, Hops Laif (Bayer): >>10 Mio St. Johns Wort Kytta Sedativum (Merck): Valerian, Hops, Passionflower Neurapas (Pascoe): Valerian, SJW, Passionflower 44

45 Calm and sleep drug bestsellers 2017 Valerian Passion flower St. Johns Wort Hops Melissa 45

46 Selected other bestsellers 2017 Priorin (Bayer) / hair growth women Millet extract Granufink (Omega) / Urinary Saw Palmetto, Pumpkin seed Contractubex (Merz) / Scars treatment Onion extract 46

47 Others drug bestsellers Saw Palmetto Millet Still Ginseng, recovers after problems due to extreme high price level 47

48 Introduction The nature network Raw Material Extract as Active Ingredient Herbal Medicinal Product Regulatory Affairs Markets and Products Summary 48

49 Summary Prerequisites for high standard quality and succesful phytopahrmaceuticals Ensurement of traceability from the drug to the finished product Cultivation, controlled collection & documentation of the raw material are of highest importance Validated production process necessary to guarantee batch to batch consistent extract quality Herbal medicinal products need a registration under pharmaceutical guidelines 49

50 Summary and outlook Advantages of Phytomedicinical products Registered products are high margin products Registered products offer the advantage of a long life cycle Registered products are increasing the image of a health product company in the market 50

51 Summary and outlook General trends and perspectives Consolidation of the german and worldwide market for herbal products keeps going on Only Quality products with good science and safety records survive both for Pharma and dietary supplement products. Upgrade of Traditional Medicine to modern Phytotherapy More restrictions on health food claims move to more regulated or pharmaceutical legislation 51

52 Thank you! 52

53 Links Contact Dr. Rainer Kunz Finzelberg GmbH & Co. KG Koblenzer Str Andernach Germany Phone.: Fax.:

54 Copyright and liability We emphasise that the contents of this presentation constitute works subject to protection under the laws of copyright. Any reproduction, dissemination, further processing or other use of the presentation, of the information and contents thereof, or of corresponding excerpts thereof, shall be subject to our express consent. The presentation was drawn up to the best of its authors knowledge and belief and is offered for information purposes. Absent further agreement, any information or contents found therein shall serve as non-binding indications only and shall represent no promise or pledge. The authors of the presentation cannot accept liability for damage that may arise as a result of utilisation of the information and contents of which the presentation consists, unless information and contents of which the presentation consists have been made part of a concrete agreement as between our customer and us. 54