Saneca Pharmaceuticals API Business Presentation 2016

Saneca Pharmaceuticals: Perspective

Saneca: Excellent location in Europe

• Slovakia is an EU member state • Attractive geographical location close to Vienna, Budapest and Prague, with

excellent logistic links • Stable environment for business, EURO currency country • Located in a country with competitive cost of manufacture and low levels of

inflation

Saneca: Company Milestones Foundation of Slovak Alkaloids focused on production of

morphine

Creation of new national company Slovakofarma Hlohovec continuation of alkaloids production;

Establishment of pharmaceutical and API´s production

Privatisation of Slovakofarma Hlohovec

Merger with Czech Léčiva – Zentiva creation

Acquisition of Zentiva by Sanofi-Aventis

Acquisition by Wood Pharma Holding

Formation of new independent company Saneca Pharmaceuticals

1941

1950

1994

2003

2009

2012

2013

cGMP KILOLAB Investment 2016

API Key Facts: General Introduction

More than 70 year long tradition in API manufacturing

Wide extent of chemical and technological expertises from vegetal extraction to multi-step synthesis

cGMP certified production units

30 active products are in portfolio:

23 Active Pharmaceutical Ingredients

5 API intermediates

2 pharmaceutical excipients (with cGMP certificate)

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API Key Facts: General Introduction

API Sales level of approx. K € 19.000 (in 2015)

API Production output of approx. 90.500 Kg (in 2015)

API Export Sales to more than 35 countries

Key sales territories: Europe, South Korea, Japan, Canada

Others: India, Latin America, Ukraine, Middle East countries, CIS countries, North Africa etc.

... and of course the local market of Slovakia

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API Key Facts: Saneca Production Site

API Operation area: 20 900 m2

API Staff: 113 people

- Production 70

- Process Eng./IPC/R&D 26

- Technical Support 17

API Key Facts: Organization of Manufacturing Units

API Production

Synthesis Opiates

„VVZ“ Plant

Multipurpose Plant

Synthetic Opiates Unit

Codeine & Morphine salt Units

Morphine extraction Unit

Kilolab

API Key Facts: Processes & Equipment PROCESS DESCRIPTION OF PROCESS/EQUIPMENT

Reaction / reactors 141 batch reactors; total mixing capacity 190.000 liters; SS and GL; volume from 60 to 6 000 liters (non-GMP lab scale of glass 20 liters)

Catalytic processes Catalytic hydrogenation (low and high pressure) 4 pcs; max. 4 Mpa

Separation solid – liquid Filtration and centrifugation: 22 pcs

Separation liquid – liquid Extractions of water / organic solvent

Absorption Disposal of emissions, absorption of gases

Adsorption ion exchange, adsorption on solid surface

Distillation, rectification Distillations, rectifications, molecular distillation

Crystallization Under controlled conditions

Drying Vacuum drying under nitrogen flow, and fluid drying under controlled humidity conditions

Number of equipment for drying: 20 pcs

Particle size modification (final treatment) Sieving, milling, micronization: 13 pcs

Recycling of solvents Recovery of solvents from processes

Isolation from natural MT Isolation of morphine from poppy straw

REACTION Amidation Detritylation

Amination reductive Dieckmann condensation

Aminolysis Epimerization

Aminomethylation Epoxidation

Carbamate hydrolysis Esterification

C-alkylation Enolization

C-C bond coupling (ethynylation) Friedel Crafts acylation

Claisen condensation Grignard reaction

Clemmensen reduction (modified) Hydrogenation catalytic

Condensation Hydrolysis

Cyclization Chlorination

Crystallization of diastereomeric salts Chlorosulfonation

Debenzylation catalytic Isomerization

Deprotection Lactonization

Demethylation, N- Mannich reaction

Malonester synthesis Oxidation

N-acylation Silylation

N-alkylation Reduction with hydrides

N-arylation Resinate formation

O-alkylation Schiff reaction

S-alkylation Urethane synthesis

API Key Facts: Reaction Capabilities

API Key Facts: Core Competencies

1 • Development (screening, lab scale development)

2 • Analytical method development

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• Scale-up and industrialisation of the proposed technologies experience in a wide range of reaction capabilities

4 • Stability testing of intermediates and regenerated solvents

5 • Product transfer and manufacturing including relevant documentation

6 • Process and cleaning validation

7 • Continuous improvement of the technologies

8 • Risk analysis

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• Preparation of required data for DMF and CEP submission including solving of deficiency letters

API Key Facts: Open to CMO co-operations... Our Commitment:

To provide highest quality standards available.

To build long-term based cooperation and act in an ethical way.

To provide high level of customer service.

API´s Contract Manufacturing Offer:

• R&D support with Kilolab manufacturing facility.

• Scale-up capability from laboratory to commercial.

• Flexible range of batch size:

from 1 to 30 kg/batch for Kilolab.

from 30 to 700 kg/batch for commercial scale units.

• Full support with analytical method transfers, process improvements.

• Controlled Substance License available.

• Highly experienced team in regulatory & QA/QC processes.

Latest local authority´s GMP inspection for API´s performed by ŠÚKL (State Institute for Drug Control) in 06/2014.

No critical observations

-> EU GMP Certificate valid until 06/2017

PMDA – inspected in 09/2014

MFDS – inspected in 08/2010

US FDA – inspected in 12/2007

Customer Audits in 2015 – 17 audits at Saneca

All customer audits successful with no critical observations.

API Key Facts: Inspection & Audit Track Record

API Key Facts: Regulatory Affairs & QA/QC

Highly skilled team with long-term experience.

CEP´s / DMF´s (US & CTD) – capability in documentation preparation and management:

14 granted CEP´s,

4 CEP´s pending,

21 DMF´s available.

„State of the Art” QC laboratories:

In-house raw material, IPC and final product release testing,

Stability study testing (including Zone IV B),

Equipped to the level of internal needs (HPLC, GC, Laser Diffraction,

Xray, DSC, microbial purity… etc.).

Formulation Production Organization

Pharma Production

Solid Dosage Form Liquid Dosage Form Semisolid Dosage Form

Granulation Tabletting

Effervescent Coating

Pellets

Packaging

Liquid Production

Soft Gelatine Capsules

Ointments

Liquid Dosage Form

4 billion tablets

3 400 tons

25 mil. bottles, 220 mil. capsules

nonsterile liquids (solutions, drops, syrups)

uncoated, coated (sugar/film) Tablets

Liquids

vitamins Effervescent

registered vitamins, food supplements

Soft gel capsules

medical and cosmetic creams, ointments, gels, toothpastes Semisolids

filled by powders, granules, pellets

Hard gel capsules

coated (protection/masking/release – modification), mul- tiple unit systems, filled capsule or compressed in tablet Pellets

Formulation Capabilities – dosage forms

Drug Products Manufactured

ACETYLCYSTEINE

ACETYLSALICYLIC ACID

ALPHA-TOCOPHERYL

AMITRIPTYLINE

ATORVASTATIN

BETAXOLOL

BISOPROLOL

CAFFEINE

CELECOXIB

CIPROFLOXACIN

CITALOPRAM

CODEINE PHOSPHATE

DESLORATADINE

DIAZEPAM

DICLOFENAC

ESCITALOPRAM

FEXOFENADINE

ITOPRIDE

LOSARTAN

MELOXICAM

METFORMIN

METOPROLOL

OMEPRAZOLE

PARACETAMOL

PENTOXIFILLINE

PERINDOPRIL

PRAMIPEXOLE

QUETIAPINE

RAMIPRIL

RISEDRONATE

SILDENAFIL CITRATE

SODIUM FLUORIDE

SOLIFENACIN

SUMATRIPTAN

TAMSULOSIN

TERBINAFINE

TRAMADOL

VENLAFAXINE

ZOLPIDEM TARTRATE

In total more than 70 different API´s

Thank you very much for your attention