Active Phytopharmaceutical Ingredients

Pharma Asia 2017, 22.08.2017

Finzelberg’s role in developing

Successful herbal medicinal products –

From plants to modern herbals

1

Dr. Rainer Kunz

Welcome to the nature network®

2

Raw Material Extract as APIHerbal

MedicinalProduct

RegulatoryAffairs

Markets andProducts

Summary

3

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-HoldingGermany

• TO > 500 Mio €

4

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

Welcome to Finzelberg

Active phytopharmaceutical ingredients paired with regulatory support

Functional ingredients & concepts ready to use for food supplements

6

How can we guarantee Safety, Efficiency and

Quality of herbal medicinal products?

Value creation chain with highest traceability

and sustainability

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8

• Raw Material

• Extract

• Herbal Medicinal Product

• Registration Process

• Marketing

9

Introduction

The nature network

Raw Material Extract as

ActiveIngredient

HerbalMedicinalProduct

RegulatoryAffairs

Markets andProducts

Summary

Raw Material

Quality right from the start

10

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.)

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Quality of the raw material

EMEA guidelines

Guideline on Good Agriculture and Collecting Practice

EMEA / HMPC / 246806/2005 (GACP) covers the

following:

• Quality assurance

• Personnel and education

• Building and facilities

• Equipment

• Documentation

• Cultivation

• Collection

• Harvest

• Primary processing

• Packaging

• Storage and distribution12

Influence on a positive development

Improvements of the drying process

14

Traditional Drying areas Drying areas after upgrade

Influence on a positive development

Improvements of the storage

15

Raw Material without GMP Raw Material with GMP

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the nature network®

the nature network® 16

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

99 % raw material supply to Finzelberg with

100 % traceability !

17

Introduction

The naturenetwork

Raw Material Extract as

ActiveIngredient

HerbalMedicinalProduct

RegulatoryAffairs

Markets andProducts

Summary

The production process

The following production types are predominantly used at

Finzelberg

• Maceration (tea-type)

• Percolation (espresso-type)

More sophisticated production types are used at Finzelberg as well:

• Counter current extraction

• Liquid-liquid extraction

perkolator

4

perkolator

3

perkolator

2

perkolator

1

25-90°C

herb

/ s

olv

ent ra

tio =

1:6

- 1

:35

18

Extraction solvents

The following solvents are commonly used at Finzelberg

• water

• ethanol

• methanol

__________

• acetone

• ethyl acetate

19

TLC of Valerenic acids (DAB 1999) TLC of volatile oil (Finzelberg)

VS = Valerenic acid OH-VS = Hydroxyvalerenic acid

Extract development -

Influence of solvent on API

20

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

….

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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

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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

Quality standards within the nature network®

the nature network® 232015

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Introduction

The naturenetwork

Raw Material Extract as

ActiveIngredient

HerbalMedicinalProduct

RegulatoryAffairs

Markets andProducts

Summary

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

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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)

The Herbal Medicinal Product

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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

The Herbal Medicinal Product

2828

the nature network®

the nature network® 28

the nature network® is the umbrella for Martin Bauer Group, PhytoLab,

Europlant Group.

29

Introduction

The naturenetwork

Raw Material Extract as

ActiveIngredient

HerbalMedicinalProduct

RegulatoryAffairs

Markets andProducts

Summary

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

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The Dossier

CTD triangle

• Organized into five modules

• 1st module is region

specific

• Modules 2, 3, 4, 5 are

common for all regions

• Monographs and clinical

studies

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3.2.S Raw Material3.2.S.1 General Information

3.2.S.1.1 Nomenclature

3.2.S.1.2 Structure

3.2.S.1.3 General Properties

3.2.S.2 Manufacture (Production)3.2.S.2.1 Manufacturer(s)

3.2.S.2.2 Description of manufacturing process and process controls

3.2.S.2.3 Control of materials

3.2.S.2.4 Controls of critical steps and intermediates

3.2.S.2.5 Process validation and/or evaluation

3.2.S.2.6 Manufacturing process development

3.2.S.3 Characterisation3.2.S.3.1 Elucidation of structure and other characteristics

3.2.S.3.2 Impurities

Module 3 - Quality of active substance

Table of content

32

3.2.S.4 Control of drug substance3.2.S.4.1 Specification

3.2.S.4.2 Analytical Procedures

3.2.S.4.3 Validation of analytical procedures

3.2.S.4.4 Batch analyses

3.2.S.4.5 Justification of Specification

3.2.S.5 Reference Standards or Materials -- from Phytolab

3.2.S.6 Container Closure System

3.2.S.7 Stability -- by Phytolab or Finzelberg3.2.S.7.1 Stability summary and conclusions

3.2.S.7.2 Post-approval stability protocol and stability commitment

3.2.S.7.3 Stability data

Module 3 - Quality of active substance

Table of content

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3.2.P DRUG PRODUCT

3.2.P.1 Description and composition of the drug product

3.2.P.2 Pharmaceutical development

3.2.P.3 Manufacture

3.2.P.3.1 Manufacturer(s)

3.2.P.3.2 Batch formula

3.2.P.3.3 Description of manufacturing process and process controls

3.2.P.3.4 Controls of critical steps and intermediates

3.2.P.3.5 Process validation and / or evaluation

3.2.P.4 Control of excipients3.2.P.4.1 Specifications

3.2.P.4.2 Analytical procedures

3.2.P.4.3 Validation of analytical procedures

3.2.P.4.4 Justification of specifications

3.2.P.4.5 Excipients of human or animal origin

3.2.P.4.6 Novel excipients

3.2.P.5 Control of drug product

3.2.P.5.1 Specification(s)

3.2.P.5.2 Analytical procedures

3.2.P.5.3 Validation of analytical procedures

3.2.P.5.4 Batch analyses

3.2.P.5.5 Characterisation of impurities

3.2.P.5.6 Justification of specifications

3.2.P.6 Reference standards or materials3.2.P.7 Container closure system

3.2.P.8 Stability

Module 3 - Quality of active substance

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Worldwide partnerships

with CMO‘s and partners

allow fast development

and rapid market access!

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Introduction

The naturenetwork

Raw Material Extract as

ActiveIngredient

HerbalMedicinalProduct

RegulatoryAffairs

Markets andProducts

Summary

Classification of finished herbal products – a

challenge for regulatory affairs departments!

Food

Herbal

Medicinal

Products

Cosmetics

Medical

Devices

Novel

FoodFood

supplements

Dietarysupplements

Pharma

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Product focus

• Legal regulations & defined rulesfor access to market & sales

• Transparent situation for the evaluation of necessary investment

• Long life-cycle of product

Herbal

Medicinal

Products

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38

Estimated size of herbal markets worldwide in

€ TO (2017)

Total world market

for herbals of all

types

estimated 100

BilionUSA

???

Germany

1,2 Bilion

Asia

???

Europe

4 Bilion

German Herbal Pharmacie market facts 2016

• 80 % 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

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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

Total 1,200

In 2004

withdrawal of

reembursement!

Nevertheless after

transition phase

recovered stable

OTC market

Source: IMS Health

Some „famous“ registered herbal medicinal

products in the german pharmacy market

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Cough and Cold herbal „Bestsellers“

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• Sinupret (Herbal mixture)

> 50 Mio €

• Umckaloabo (Pelargonium root)

> 20 Mio €

• Prospan (Ivy leaf)

>> 10 Mio €

Bronchicum

>> 10 Mio €

• Silomat (Althaea Root)

from Boehringer / Sanofi

Plerus (Pelargonium root)

Saudi Arabia

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Cough and Cold drug „Bestsellers“ and Trends

• Primrose

• Thyme

• Ivy

• Pelargonium

• Plantaginis Lanceolata

• Marshmallow

Calm and sleep„bestsellers“ 2017

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• Baldriparan stark + Beruhigung (Pfizer): >> 10 Mio €

• Laif (Bayer): >>10 Mio €

• Kytta Sedativum (Merck):

• Neurapas (Pascoe):

Valerian Melissa, Hops

St. Johns Wort

Valerian, Hops, Passionflower

Valerian, SJW, Passionflower

45

Calm and sleep drug „bestsellers“ 2017

• Valerian

• Passion flower

• St. Johns Wort

• Hops

• Melissa

46

Selected other „bestsellers“ 2017

• Priorin (Bayer) / hair growth women

• Granufink (Omega) / Urinary

• Contractubex (Merz) / Scars treatment

Millet extract

Saw Palmetto, Pumpkin seed

Onion extract

47

„Others“ drug „bestsellers“

• Saw Palmetto

• Millet

• Still Ginseng, recovers after problems due to extreme high price

level

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Introduction

The naturenetwork

Raw Material Extract as

ActiveIngredient

HerbalMedicinalProduct

RegulatoryAffairs

Markets andProducts

Summary

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

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Summary and outlookAdvantages 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

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Summary and outlookGeneral 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

Thank you!

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Links

Contact

Dr. Rainer Kunz

Finzelberg GmbH & Co. KGKoblenzer Str. 48 - 5656626 Andernach Germany

Phone.: +49 2632 924 – 171Fax.: +49 2631 924 – 49 – 171

rainer.kunz@finzelberg.de

http://www.the-nature-network.com

http://www.martin-bauer-group.com

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