Świat Przemysłu Farmaceutycznego 3/2009 EN

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Comprehensive Cleaning and Disinfecting Solutions for the Pharmaceutical Industry.

We supply: • cleaning and disinfecting products - ClearKlens and Titan brand products for the pharmaceutical industry - full documentation, approvals, certificates - validation methods - products for sterile areas *

• technical solutions - construction and modernisation of CIP stations - chemical dosage systems - scrubers and manual cleaning equipment

• personal hygiene solutions • technical service, procedures, training, support, consultancy

* preparations for sterile areas – available from 2010

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JohnsonDiversey Polska Sp. z o.o. ul. Fabryczna 5, 00-446 Warszawa Tel. +48 22 328 10 00 Mobile phone +48 601 86 90 33 Fax +48 22 328 10 01 www.johnsondiversey.com

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R.BOSCH GmbH – Pharma Solid www.pa.bosch.com • capsule fillig machines, checkweighers, blister lines, cartoning machines

R.BOSCH GmbH – Pharma Liquid www.pa.bosch.com • washing machines, sterilizing tunnels, filling lines, isolator technology, leak control of ampoules and vial

R.BOSCH GmbH - SBM www.sbm-a.at • sterilizers, stoppers washing and sterilization

R.BOSCH GmbH - Moeller & Devicon www.m-d.dk • inspection lines, assembly lines

R.BOSCH GmbH - Pharmatec www.pharmatec.de • high purity media systems, process and bio systems

GLATT GmbH, www.glatt.com • wet granulators, fluid bed dryers and granulators, coaters, material handling systems, sieves for wet and dry products

MUELLER GmbH www.mueller-gmbh.com • stainless steel containers and dosing systems, material handling and mixers

PESTER www.pester.com • packaging, robots and palletizers

PCE Pharmacontrol www.en.pharmacontrol.de • camera image processing, code scanning, track and trace systems

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42 production

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Polish industry

Strategic Implications of Packaging Choice in the Generic Sector

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Tablets Coatings – a historical review

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The design of a BMS

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PAT – how to achieve a good process?

28 Qualifi cation Of Thermostatic Equipment In Pharmacy 30

The Principle of Diversity

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Recirculation: Stop without any consequences

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A new subsidiary in Spain

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Pharmaceutical label – an example of product label evolution

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The privatization of Polfa Pabianice

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Patent protection of pharmaceutical inventions

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Euroregional Pharmacy Centrum

40 ONCO - 3CLA 41

Bioton i Bayer Schering Pharma in China

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Organized by the Farmacom publishing house and the quarterly Świat Przemysłu Farmaceutycznego (“World of the Pharmaceuticals Industry”), the Congress took place on 25–26 June 2009 at Andel’s Hotel, Łódź.

The honorary host of the Congress was the pharmaceuticals manufacturing company Polfa Łódź SA.

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48 Polish industry

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Celon Pharma joins the best

47 Extend the company’s factory in Ksawerów 48

Avena

conferencess, fairs, training

50 BioForum 2009

reports, projects, plans

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Pharmaceutical biotechnology in Poland

54

Report on the situation in the pharmaceuticals industry

download *.pdf version: www.farmacom.com.pl

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From the editors: I am pleased to present you with another bilingual edition of the “World of the Pharmaceutical Industry” quarterly, describing this year’s numerous industry events taking place in Poland and abroad.

FARMACOM Publishing Company proudly informs that our NEW QUARTERLY – “WORLD OF THE COSMETIC INDUSTRY” – will appear on the market soon. It will reach all cosmetic industry manufacturers in Poland and institutions, organizations and companies related to the industry.

List of advertisers: Adamus HT Sp. z o.o.

Bio-Chic Sp. z o. o.

BOCCARD POLSKA Sp. z o.o.

In the coming issue of the „World of the Cosmetic Industry”: - packaging in the cosmetic industry - production control and quality assurance - report on the safety of cosmetics - hygiene in the production process - GMP in the cosmetic industry - logistics - reports from conferences and many more Enjoy the reading.

DRUK-PAK S.A. ECOLAB Sp. z o.o.

FM LOGISTIC GAL I.E.S. International Polska Sp. z o.o.

- MARCHESINI GROUP S.p.A. I.E.S. International Polska Sp. z o.o.

Editor-in-chief „Świat Przemysłu Farmaceutycznego”

Programme Board: Leszek Borkowski DPharm Andrzej Szamański President of ISPE Poland, Quality Director at Polpharma SA Pharmaceuticals Irena Rej President of the Polish Pharmaceuticals Chamber of Commerce

Zbigniew E. Fijałek director of the National Institute of Medicines Marcin Kołakowski head of the Supervision Department of the Central Pharmaceutical Inspectorate.

- PADANA CLEANROOM IKA-TECHNIK Sp. z o.o. i ZMR S.C. INFODRUK JohnsonDiversey Polska Sp. z o.o.

Natoli Engineering Company O’HARA TECHNOLOGIES OPTIMA GROUP pharma GmbH Patpol Sp. z o.o.

PHZ i ITH INTREX POL-EKO-APARATURA sp.j.

PPU „COMEX” Sp. z .o.o.

PROBIT TRADE&CONSULT Sp. z o.o.

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Quarterly, published by FARMACOM Wodzisław Śląski 44-300 ul. 26 Marca 31/11 farmacom@farmacom.com.pl www.farmacom.com.pl Editor-in-chief Robert Miller tel./fax +48 032 455 31 61 tel. kom. +48 502 084 101 robert.miller@farmacom.com.pl Subscription and distribution Publisher FARMACOM Wodzisław Śląski 44-300 ul. 26 Marca 31/11 tel./fax +48 032 455 31 61 prenumerata@farmacom.com.pl Issue price „ŚPF” – 10 zł Annual subscription price – 35 zł

Payments may be made to the account: ING Bank Śląski O/Wodzisław Śląski 56 1050 1403 1000 0023 2091 8119 Editors Maria Kubsz, Tomasz Butyński, Teresa Kubsz-Miller tel./fax +48 032 456 60 79 redakcja@farmacom.com.pl Proofreading: Maria Gniłka DTP: Wiktor Adamiec wiktor.adamiec@farmacom.com.pl Printing: Drukarnia BIMART. Number of copies printed: 2 500 Partner:

www.ispe.org.pl

The magazine is addressed to process and production engineers, automatic systems specialists, heads of production, control and quality assurance divisions, heads of logistics and procurement divisions and product development divisions at pharmaceutical companies. The magazine is also purchased by organizers of trade fairs, conferences and industry training courses, government offi ces, ministries, institutes, higher educational institutions offering pharmaceuticals-related courses, and design fi rms. The editors reserve the right to shorten and edit material.

The editors are not responsible for the content of advertisements. The use of materials and publication of advertisements produced by the publisher is permitted only with the editors’ consent.

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www.farmacom.com.pl

2009-09-11 22:15:08

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congress Organized by the Farmacom publishing house and the quarterly Świat Przemysłu Farmaceutycznego (“World of the Pharmaceuticals Industry”), the Congress took place on 25–26 June 2009 at Andel’s Hotel, Łódź.

The honorary host of the Congress was the pharmaceuticals manufacturing company Polfa Łódź SA.

T

he Congress was attended by pharmaceutical companies’ CEOs, R&D directors, process maintenance specialists, technology specialists, automatic systems experts, heads of production, control and quality assurance, and heads of logistics and procurement – a total of more than 140 people representing the leading pharmaceuticals plants and fi rms.

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The high standard of the material presented at the Congress was assured by experts from Łódź Medical University, the Central Sanitary Inspectorate, the Pharmaceutical Institute, the Central Pharmaceutical Inspectorate, the National Institute of Medicines, and the Institute of Logistics and Warehousing. Speakers also included experts from pharmaceuticals manufacturers download *.pdf version:

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congress

and other fi rms with operations linked to the pharmaceuticals industry.

The Congress programme was organized so that successive thematic blocks corresponded to the successive stages of production at pharmaceutical plants.

Next to the lecture theatre were exhibition stands, where a large number of fi rms displayed what they had to offer to the pharmaceuticals industry.

Honorary patrons of the Congress included the Office for Registration of Medicinal Products, Medical Devices

download *.pdf version: www.farmacom.com.pl

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Design Argento e China

congress and Biocidal Products, the Institute of Logistics and Warehousing, the National Medicines Institute, the “Pharmacy Poland” Chamber of Commerce, the Polish Pharmaceutical Association, the chief executive of Łódź Province (Włodzimierz Fisiak) and the Mayor of Łódź (Jerzy Kropiwnicki).

Patrons of the programme of the Congress were ISPE Poland and the Rector of Łódź Medical University, Professor Paweł Górski MD.

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The Congress ended with a tour of the production sections of the Polfa Łódź pharmaceuticals manufacturing plant.

WE ARE ALREADY PLEASED TO INVITE YOU TO THE NEXT CONGRESS IN A YEAR’S TIME.

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www.farmacom.com.pl

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M

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CM

MY

CY CMY

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Everything you may need for syringe packaging

Design Argento e China

Marchesini Group is your unique partner for filling, handling, labelling and packaging syringes. Everything under one roof.

- Automatic machine for loading and positioning products in single-line from bulk - Feeding syringes from hypak nest - Feeding syringes or safety device from rondo flat tray traditional or robotized systems - Retrayer: handling equipment to collect syringes into rondo flat - Traybuffer “FIFO�: handling equipment to buffer syringes into tray - Renester: handling equipment to collect syringes into nest - Safety device assembling machine - Backstop assembling machine

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Plungering, labelling and assembling machines combi Filling and stoppering machines High speed labelling machines Deep draw thermoformers Cartoner with Robotized automatic syringes loading systems Robocombi Robovision Robomaster End of line equipment

MARCHESINI GROUP S.p.A. via Nazionale, 100 - 40065 Pianoro - Bologna - Italy sales@marchesini.com - www.marchesini.com

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www.ies.pl

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Fette Die Segments Manufactured by Natoli …the only licensed manufacturer.

Natoli is proud to be the only licensed manufacturer of Fette die table segments.

Natoli’s advanced system of micro-precision engineering, manufactures Fette die segments of exceptional quality that are delivered quickly, worldwide at competitive prices. Natoli manufactures standard round, special shape, multi-tip and carbide lined die segments.

Natoli Engineering Company, Inc. P: +1 636.926.8900  sales@natoli.com  natoli.com

Local Natoli Representatives Contact Information: Natoli Europe, a division of Casburt TMS UK/Ireland/Europe P: +44 1782 332511 F: +44 1782 501501 info@casburt.com

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Natoli Scandinavia Denmark/Norway/Sweden P: +45 5819 0941 F: +45 5819 0741 jens@natoli.dk

MAQFA Spain/Germany P: +34 93 212 4034 F: +34 93 212 4594 jms@maqfa.com

ACM France P: +33 34 462 1111 F: +33 34 457 2208 stephane.delarue@acm-outil.com

2009-09-11 22:16:15 8/25/09 12:52:08 PM

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Strategic Implications of Packaging Choice in the Generic Sector

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he Honeywell Generics Forum, held in January 2009 in Brussels, brought together over 20 senior management attendees from 15 companies in 11 countries for a topical debate on the current issues facing the industry as well as to examine new packaging strategies.

Highlighted at the Honeywell Generics Forum The generics sector has been experiencing an unprecedented period of growth and generic fi rms are set to further capitalise on the opportunities offered by patent expiry on an estimated $150 bn worth of revenues by 2015. Generics contribute to the long-term affordability of healthcare systems. Drivers such as aging populations, increasing medical consumption, cost containment and restrictions in government healthcare budgets have all brought about increasing focus on the cost savings offered by the generic drug industry. On closer examination; however, this is an industry in transition as

the implications of existing trends work their way through the sector: • Increasing pressure to lower drug costs as healthcare cost containment gains greater impetus driven by the Economic Crisis • Globalisation of the industry increasing pressure for companies to develop both regional and global strategies • Fewer launches by innovators in recent years will translate into fewer opportunities for generic companies down the line • Increasing number of originator evergreening strategies to stop generics coming to market The result will be intense competition and to survive generic companies need to seriously improve product profi tability while avoiding commoditisation through innovative competitive strategies … e.g. packaging.

download *.pdf version:

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production

This paper reports on the issues highlighted at the recent Honeywell Generics Forum and examines the strategic implications of packaging choice in the generics industry. It looks at how companies are leveraging ultra high barrier thermoform solutions like Aclar ® to create new value propositions. Meeting regulatory and quality needs are a basic standard and a given requirement for any primary packaging solution. However, in order to meet the challenges of today’s generics marketplace, innovative generic companies are now looking beyond these basic technical needs and are optimising packaging platform choice to realise market advantage and profi tability gains. It is now recognised that pack differentiation offers an ideal opportunity to create a sustainable competitive market advantage.

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production

Generic companies need to fi nd cost savings and effi ciencies to maintain profi t margins. One approach is to standardise primary packaging as much as possible on effi cient high barrier thermoforming solutions such as Aclar ®.

Alu/Alu Pipeline Recent market research conducted by Honeywell with generic manufacturers highlighted some major concerns: • Large numbers of pipeline products packed in Alu/ Alu even when not necessary for barrier reasons • Increasing Capex required to accommodate latest Alu/Alu pipeline • The need to increase OEE and plant utilisation • Internal strategic marketing teams demanding differentiated packaging to exploit profi t pools • Wholesalers and pharmacies both demanding smaller pack sizes Not all products packed in Alu/Alu actually need to be in Alu/Alu – many can be moved to high barrier thermoform materials. But why does the generics sector continue to use so much Alu/Alu? The answer often results from 2 simple reasons … fi rstly generic companies are copying originator choices, and secondly they are not fully considering all packaging options in the development phase. Generic companies can be too restrictive in material choices with only 2-3 materials on stability.

At the time of patent expiry the originator’s packaging decision may be 16 years old. It was probably taken in a hurry with little regard to pack size and prior to the launch and common use of ultra high barrier thermoform materials. Therefore the major question for generic developers is: “Do we really want to copy an old product or should we develop something better?”

Generics Can Be Different Generic drugs are pharmaceutical preparations that contain the same active ingredients in the same concentration as the originator product. On one hand they must be therapeutically equivalent to the originator drug; but on the other, the generic product’s shape, size, colour ... and packaging material can be different and better!

The old maxim: “originators innovate while generics differentiate,” is often forgotten in the race to get a new product to market. Pack differentiation is an ideal opportunity to create a sustainable competitive market advantage. Increased marketing considerations during the generic development phase are already tipping the balance in favour of high barrier thermoforming - a process which enables a broader selection of design possibilities for a differentiated pack solution.

Packaging Decisions Pharmaceutical packaging is no longer purely functional. It can deliver value both internally (improved operational effi ciency, reduced complexity, reduced total costs) and to the end-user (wholesalers, patient, care-giver); but to leverage this value, packaging decisions should result from informed, cross-functional, collaborative processes. Primary packaging decisions that may have been correct for R&D during development may not be correct, or may even hamper, manufacturing operations and marketing post launch and for years to come. The strategic impact of packaging choice on crucial factors such as pack size, total costs and machine utilisation is often not fully considered.

Increasingly generic companies are choosing to revisit packaging choices. Many have already initiated a switch-OUT strategy1 and are turning existing “ineffi cient packs” into “effi cient packs.” Others are initiating switch-IN strategies2 and building packaging material fl exibility into their development process by adding a high barrier thermoform material such as Aclar ® to their stability protocols.

Thermoforming Advantages One of the greatest challenges for generic companies is managing very large drug portfolios often consisting of 200+ drugs in multiple pack variants for different countries. This vast array of products and packs creates massive complexity in packaging and operations and drives up costs. The situation has been further complicated by industry consolidation with some companies struggling to maximise site and machine utilisation across multiple sites, multiple geographies and multiple, non-uniform capabilities.

Initial packaging material choices have far-reaching and long-lasting impact. The choice affects total packaging costs beyond the cost of material per square meter due to factors such as: cost of secondary materials, material usage, scrap rate, maintenance and

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Aluminium Cold Form Versus Aclar Thermoform For Capsule Size 0

production rates, etc. In addition, choice of packaging platform has major supply chain implications. Industry feedback strongly indicates that pack size can be the main differentiator after price for major wholesalers and pharmacies.

Figure 1 demonstrates that by choosing an ultra high barrier thermoform material such as Aclar ® instead of Aluminium Cold Form Foil can result in a 55% reduction in pack size.

Thermoform packaging can dramatically increase tablet density providing cost savings across the board.

The increase in tablets packaged per machine stroke increases the effective capacity and speed of each packaging line compared to Aluminium Cold Form Foil.

Faster production rates and the ability to use machines interchangeably can be translated into fewer packaging lines required, lower maintenance labour costs, and lower capital equipment expenditures. Thermoforming offers increased production capacity and fl exibility which impacts on the bottom-line and a major reason why many generic fi rms are now developing robust Switch-IN and Switch-OUT strategies - see Figure 2.

Switch-IN Adding a high barrier thermoform material to a stability protocol can have a relatively low impact on development time, resources and costs while increasing the potential for launch in the most advantageous material.

This in turn can potentially offer substantial benefi ts in downstream costs and effi ciencies as well as increased sales. Generic companies are greatly increasing their product advantage by simply adding Aclar ® to stability studies.

Switch-OUT Switch-OUT is a process to change an existing launched product from Alu/Alu to an ultra-high thermoform pack e.g. Aclar ®. The resultant reduction in pack size and increased effi ciencies offer many advantages to Generic fi rms.

There are cost and resource implications in making this variation but increasingly generic companies are fi nding that resources spent maximising the profi tability of existing packs can offer greater returns than launching new products alone. Smart companies are now choosing to piggyback material switch-OUT on top of existing scheduled variations.

Conclusion Ever strengthening competition in the generics sector is placing more importance on creating and exploiting a competitive advantage through packaging choice.

A marketing advantage can be achieved by offering wholesaler and pharmacy advantages through an improved pack format. Equally a competitive advantage can be obtained by cost reduction and/or effi ciency gains thus improving product margins and overall portfolio profi tability.

Choice of packaging platform has strategic implications for generic fi rms because it can have profound implications on overall company profi tability. Standardising where possible on high barrier thermoforming materials such as Aclar ® can enable generic companies to reduce complexity costs, improve operational fl exibility and overall profi tability. While Cold Form Foil has a vital part to play in blistering in the future, when total barrier is not required generic fi rms have much to gain by moving to a high barrier thermoform solution.

1

Migrating a product already launched in Alu/Alu into an ultra high barrier thermoform pack

2

Migrating a product out of Alu/Alu and into an ultra high barrier thermoform material prior to launch download *.pdf version: www.farmacom.com.pl

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Tablets Coatings – a historical review

Dariusz Lipiak, PhD Branch Coordination Pharmaceutical Industry Brenntag Polska Sp. z o.o. ul. Migdałowa 4/52, 02-796 Warszawa

1. Why coating is used in pharmaceutical formulations?

The coating is the process to cover a surface permanently or temporarily using a suitable material.

We can group the coating process into three main category: • Sugar coating • Film coating – Tablet – Particulate/pellet coating • Compression coating The coating in formulation process used: • To protect the tablet from its environment (air, light) – Active ingredient unstable in light or in the presence of humidity – For hygroscopic formulation – Oxidable active ingredient (atmospheric oxygen) • To mask bitter taste, unpleasant odour and inelegance color of the core (complete sealing of the particle surface).

• To facilitate tablet ingestion • To facilitate packing (blister) • To modify bio availability (controlled release, enteric-coated) • To separate incompatible substance by using the coat to contain one of them or to coat a pellet which was previously compressed into a core.

• To color: Tablet identification/Marketing Influence on the psychological component of treatment compliance • To complete sealing of the particle surface.

• To improve physical properties (hardness, friability reduction)

2. Sugar coating First coated tablets were obtained in the Year 1891.

Coating process was introduced as pharmaceutical technology process based on older techniques in food - fruit involucre’s by sugar which had old French name dregée. This process was largely borrowed from confectionery industry. This process was accelerated in formulations when pharmaceutical industry largely replaced open, copper, bowl-shaped pans by stainless steel. Until 1960s sugar coating were main method of masking bad taste of core and allow to obtained elegant glossy fi nish of tablets in pharmaceutical industry. The sugar coating is time-consuming process and highly skilled and jealously guarded artful knowledge of the operator. This process cannot be a fully automated and fi nal products aesthetic remains in operator hands. High coating mass in comparison with the initial product to be coated (tablet mass). Coating thickness are generally between approx. 0.5 m m and 2 m m.In sugar coating minimum weight gain over the tablets is around 40 – 50%. Sugar coating is an effective process for the application of thick coating layers, primarily for masking taste. The syrup is sprayed onto the particles, next step is in the process air evaporates the fl uid and dries the sugar coating.

When the sugar coating solution is added discontinuously, the particles remain in the process until the required coating thickness is achieved.

This list is not an exhaustive but suggest several reasons for coating tablets.

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The fi rst reference in pharmaceutical literature to fi lm tablet coating appeared in 1930 but it was until 1954 that company Abbott Laboratories produced the fi rst commercially available fi lm coated tablets.

This process using organic solvents and coating formulations based on cellulose ether polymers like methylcellulose, Ethylcellulose, Hydroxypropyl cellulose, Hydroxypropyl methylcellulose. Film coating has several advantages over the age-old process of sugar coating some of them are as follow: • Short process: Film Coating is as much a shorter process as compared to sugar coating. Normally, a 60 –70% reduction in time can be achieved.

• Weight Gain: In fi lm coating the weight gain over the tablets is around 2 - 3% and reaches only up to 10-12% for controlled release systems whereas in Sugar Coating a minimum weight gain of 40 - 50% is a normal phenomenon.

• Engravings: Film Coatings achieve the purpose of taste masking and product identification with a weight gain of 2 – 3%. Therefore, the resultant coat thickness is very thin and hence tablet engravings / break lines are defi ned very clearly without obliteration. This is an added advantages.

• Skilled operation: Sugar Coating is a highly skilled operation with practically little scope of full automation and validation. As against this the process of fi lm coating can easily be adopted and automated. Training and validation are also done with relative ease.

• Specific properties: Like light resistance, moisture resistance and selective permeability can be built into fi lm coating as per the formulation needs.

• Packing: Film Coatings gives sufficient protection against abrasion and normal humidity hence fi lm coated tablets can be blister packed with better stability profi le as compared to sugar coated tablets / drugs.

• Single stage: Sugar Coating involves multistage operation extending over 24 –32 hour Operation while film coating is a single step process normally completed in 3 – 4 hours.

• Drug release: Film Coating gives better stability to the drug formulation with thin layer of fi lm and thus better disintegration time as compared to sugar coated formulations.

Gastro soluble HPMC HPC HEC Modified starch Methylcellulose MC NaCMC PVP PVA Methacrylic acid copolymers

With these process benefits, fi lm coated tablets becomes more common.

3a. Materials used in fi lm coating and their properties

In the process of film coating a thin layer of polymer-based film is applied to a solid dosage form such as a tablet, granule or other particle. The thickness of such a coating is usually between 20 and 100 mm. Coating processes rely on a single tablet or granule passing through a spray zone, after which the adherent material is dried before the next portion of coating is received. This activity will of course be repeated many times until the coating is complete.

production

3. Film coating

a. Component of fi lm coating Film coatings are applied as a clear, white or colored systems and typically consists multiplicity of components depending on the type of system being applied. Usually Film Coating contains the following components in conventional composition: • polymer – fi lm forming agent (HPMC, other…)

– for conventional fi lm coating – for enteric fi lm coating – for modified release application • fi ller (Cellulose, other…)

• plasticizer (Macrogol stearate, esters, fatty acids…)

• dyes/opacifier (Pigments, lakes…)

• vehicle / solvent system • detackifiers ( Talc ) a1. Film-forming agents (wetting agents) Film-forming agents (wetting agents) make ability to cover a solid with a liquid fi lm. The liquid has low affi nity for the solid. The liquid forms a droplet at the surface of the solid. Addition of a wetting agent reduces the interfacial tension between the solid and the liquid. The liquid displaces the air at the surface of the solid and forms a fi lm which will cover the solid. (Table 1.)

Gastro resistant (enteric)* CAP CAT PVAP HPMCP HPMCAS Methacrylic acid copolymers Schellac

Modifi ed release Ethylcellulose EC Polyvinyl acetate HPMCAS Methacrylic acid copolymers

Table. 1.

* enteric polymers are designed to resist the acidic nature of the stomach content, yet dissolve in the duodenum download *.pdf version: www.farmacom.com.pl

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a2. Plasticizers Are simply relatively low molecular weight organic molecule, capable of modifying the physical properties of a polymer. It is generally considered that the mechanism of action for a plasticizer is for the plasticizer molecules to interpose themselves between the individual polymer strands thus breaking down to large extent polymer-polymer interactions. This action is facilitated as the polymerplasticizer interaction is considered to be stronger than the polymer-polymer interaction. Hence the polymer strands now have a greater opportunity to move past each other.

Infl uence of plasticizers: • Decreasing cohesion forces – Reduction of chain-chain interactions between polymer – Increased mobility of macromolecular chains of polymer • Physical consequences • action of plasticizers is to lower glass transition temperature (it is temperature at which a polymer “melts” – to be able to form a fi lm on tablet) • Film plasticity • Better mechanical properties • Resistance to deformation • Flexible, elastic fi lms (high modulus of elasticity) • Continuous fi lm • Allows coalescence of pseudo latexes

Common plasticizers Hydrophilic Propylene gycol Glycerin PEG Macrogol Stearate Esters , Triacetin

Hydrophobic Acetyl Monoglycerides Castor Oil DBS Phthalic esters

a3. Pigments – Dyes This group of materials are commonly used as ingredients in fi lm-coating formulae. They obviously contribute to the aesthetic appeal of the product, but they also enhance the product in other ways: • Identification of the product by the manufacturer and therefore act as an aid (not a replacement) for existing cGMP procedures.

• Colorants also aid in the identification of individual products by patients, particularly those taking multiple medication.

• They reinforce brand imaging by a manufacturer and thereby decrease the risk of counterfeiting.

• Colorants for film-coated tablets have to a greater or lesser extent opacifying properties, which are useful when it is desired to optimize the ability of the coating to protect the active ingredient against the action of light.

Dyes: water-soluble • Organic dyes which might migrate from the surface to the core. Risk of non-uniform color. Bright colors.

Lakes: insoluble • Soluble dyes adsorbed on a solid substrate (aluminum lake). No migration.

• Covering power

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Pigments: insoluble • TiO2 (is often mixed with other dyes/pigments to provide covering power play a role as a (opacifier) • Iron oxide (red, yellow, black) • Covering power a4. Fillers Increase the dry matter concentration: • To shorten the process time • To reduce the cost of the formula Examples: Lactose, MCC, pregelatinized starch (addition of MCC also significantly improves fi lm adhesion to the tablet), pregelatinized starch, talc (is also used as an antitack agent). a5. Other ingredients used sometimes • Foam inhibitors (silicones) • Brightening agents • Sweeteners • Surfactants • Water repellent agents (stearic acid) • Opacifiers ( silicates) 3c. Water Film Coating At the beginning of 1970s in pharmaceutical formulation industry introduced aqueous fi lm-coating processes.

At this time new environmental regulations came in to existence thus putting more restriction on the usage of solvent in fi lm coating processes. As a result, the pharma industry moved from organic solvent-based coatings to aqueous coatings.

A trend towards aqueous fi lm coating started gathering importance for the following reasons: • The cost of organic solvents has escalated.

• A number of regulatory authorities have banned chlorinated hydrocarbons altogether because of environment pollution.

• The development of improved coating pans and spraying systems has enabled these more difficult coating materials to be applied.

• Flameproof equipment is not required (more expensive), which reduces capital outlay and a less hazardous.

Meantime two new processing technologies, Wurster fl uid-bed process and the Accela-Cota side – vented pan was improved and developed to use water base coatings.

These technologies thus have helped in reducing dependence on conventional pan technique (with its mixing and drying limitations).

On the beginning of 1980s water fi lm coatings started to be number one process for coatings formulations of oral solid dose forms.

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Why need Ready To Use Film Coating System : Due to the following limitations in In-House film coatings, Pharmaceutical Industry has switched over to Ready Mix Film Coating System.

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Conclusion

From the technological point of view film coating is thus a sensitive balance between wetting and drying of the cores.

There is no question that film coating process remain a integral part of the overall production process for pharmaceutical industry specifically for oral solid dosage forms. However the fundamental aspects of film coating technology have changed only a little from the past 40 years but huge changes took place for coating materials and coating process conditions. We can expect that for the near future solid coating systems permit significant improvements in productivity, and adapt better to continuous processes. To justify our claims for adapting Ready Mix Film Coatings System, continuous coating process has doubled the productivity with outputs of the range from 1000kg/h to 2000kg/h meantime minimizing exposure of product to stressful process conditions like high temperature and humidity. download *.pdf version: www.farmacom.com.pl

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The design of a BMS for a pharmaceutical environment Oliver O’Reilly

There are three main phases to any BMS project — A&E Design; BMS Contractor Design/ Build; and BMS Contractor Commissioning. Phase one will be discussed in this issue of bs news while the remaining two phases will be dealt with in the April edition.

The objective of this article is to provide an overview of the issues to be addressed by the architectural and engineering (A&E) fi rm throughout the design life-cycle of a building management system (BMS) in a regulated pharmaceutical environment. There is a signifi cant difference between the level of design input required for a BMS system controlling a HVAC system in a pharmaceutical cleanroom environment, and a BMS system in, say, a commercial building.

T

his article does not seek to explain how a decision is arrived at, to subject the BMS system to a rigorous “qualification” process. However, a brief outline of the process which leads to that decision is useful.

The primary issue is system functionality — will the BMS system control a HVAC system that will be responsible for delivering a quality-critical parameter? To put it another way, could any of the ervironmental functions of particulate level, temperature, humidity or pressure control be described as “critical” in terms of maintaining product quality, If not, then they are “non-critical”.

In the regulated pharmaceutical industry, delivery of “critical functionality” must be proven. In terms of proving environmental functionality, there are a number of technically-acceptable arrangements, These will be discussed later, At a minimum, whichever arrangement is chosen, it will have to comply both with the electronic data storage requirements of the US 21CFR 11 and the documentation lifecycle requirements of GAMP 5,

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mental conditions. It also shows all instrumentation required to operate and control the HVAC plant, to maintain the reguired environmental parameters.

By both engineers working in unison, the correct type/ quantities of Instruments are selected to control the plant.

In many A&E design offices, valve/instrument Information is inputted into 3D piping/duct modelling to evaluate whether there are any design clashes, and to ensure future maintainability (eg, instrument access for in-situ calibration or maintenance).

Multi-Disciplinary Aspect Of BMS Design

In addition, the other disciplines for interaction are: • User Group- URS development; • Electrical - HVAC equipment interlocks and VFD/MCC interfaces; • IT/Automation: IT site network infrastructure; • Instrumentation: Industrial quality instrumentation; • Commissioning & Qualification (C&Q): qualification strategy & protocols; • Procurement - who buys Instruments? Project benefit from early involvement of the BMS contractor?

There are many stakeholders in the design phase of the BMS system. For a project to be a success, both the HVAC and BMS engineer should work hand-in-hand, interfacing with other disciplines to ensure the end-product meets the clients specification, Figure l shows some typical crossovers between HVAC and BMS design. The airfl ow and instrumentation diagrams (AF&ID) detail how the HVAC system will maintain the required environ-

All of this equips the BMS contractor to interpret the design and deliver a successful project.

User Requirement Specification/ Scope Of Works Document.

One of the most important stages of the BMS design is to understand and document the clients requirements for the BMS, For a BMS installation to be GAMP compliant, thedownload *.pdf version:

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Rys 1.

This shows some typical crossovers between HVAC and BMS design

se requirements must be captured in a User Requirement Specification (URS)/Scope Of Works (SÓW) document.

This document provides a description of system requirements and a basic outline for the development of the BMS, The following sections explain some of the key points which should be contained within the U RS.

BMS Overview In the pharmaceutical industry there may be a regulatory requirement (ie, FDA, IMB) to monitor and report on environmental conditions in designated cGMP areas.

Some or all of the environmental parameters in these areas may be regarded as critical to product quality. These quality critical parameters must be recorded to support cGMP manufacturing batch records.

The monitoring system is generally referred to as the EMS (Environmental Monitoring System) and the records (trends, alarms) from this system are cGMP data that must be protected/maintained. The client should conduct an impact analysis and risk assessment to determine the areas that require environmental monitoring and reporting.

There are various means of providing an EMS for the cGMP areas. Some of the options are as follows:

Qualifi ed BMS (QBMS)

In simplistic form, identify the HVAC plant which controls the qualified (cGMP) areas. For example, if there were 10 AHU’s controlling a production building, the client may identify that only eight need to be qualified. These eight AHUs would reside on o separate Qualified BMS (QBMS) system.

The remaining two AHUs (non-cGMP) would reside on a Non-Qualified BMS (NQBMS) system which typically would also include control and/or monitoring of all black utility equipment such as chillers, boilers etc.

Rys 2.

Non-qualified BMS with additional transmitter to a dedicated EMS

Even though the regulatory requirements do not apply to the NQBMS, the design and test documentation may be produced to the same standard as that for cGMP areas.

The QBMS and the NGBMS should be two distinct systems with dedicated servers, Operator Work Stations (OWS) and BMS panels, It should be noted here that the same BMS platform/hardware can be used for both systems.

Non-Qualified BMS With Additional Transmitter To A Dedicated EMS A second option is to install an additional transmitter in the cGMP areas (ie, space temperature, humidity and pressure). The NQBMS controls the operation of the HVAC plant, with only the duplicate temperature, humidity and pressure transmitters connected directly to the EMS (PLC, DCS or QBMS).

Figure 2 shows a sketch of how the system would look.

One of the drawbacks of selecting this option is the initial capital cost for the additional transmitters required, and also the ongoing calibration of both sets of Instruments throughout the lifetime of the installation, Another drawback is that both Instruments will never provide an identical reading so people are tempted to ask which one is correct? Generally, the Instruments will read within the permissible margin of error so, strictly speaking, this is not an issue.

Transmitter Signal Repeated To A Dedicated EMS A third option is to wire the environmental instruments in the cGMP areas back to the NQBMS panel as normal.

The NQBMS panel consists of two distinct physical areas — the cGMP section and the non-cGMP section. The splitter resides in the cGMP section, together with the remote base of the EMS,

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The signal from the instrument is split within the cGMP section, one output going to the NQBMS controller in the non-cGMP section and the other output going to the EMS remote base located within the cGMP section. The cGMP instrument loops are fully qualified back to the EMS. The combined NQBMS panel comes to site pre-wired and FAT tested as normal with a bus cable connecting the EMS remote base back to its respective validated system CPU All the environmental instrument in the cGMP areas can now be viewed on the validated EMS system. Figure 3 shows a sketch of the how the system would look.

The three foregoing examples give the client some options for monitoring of HVAC environmental conditions in cGMP areas. Again it can be seen that the identification of which option of monitoring of HVAC environmental conditions is important from an early stage of design (ie, if option 2 was required, duplicate transmitters with associated tags need to be added to the AF&ID’s), For the most part, our experience is that wherever the EMS model is adopted, the NQBMS system will be subjected to the same scope of design documentation as if it were a qualified system, However, the level of control on this documentation would be less rigorous. This approach provides companies with a documentation level that ensures the BMS system is properly designed and commissioned but avoids the ongoing costs of maintaining qualification for a BMS.

Redundancy The requirement, if any, for redundancy should be driven by the clients quality/project team, It is essential that the correct requirements are identified initially so that the correct BMS platform can be selected to meet the requirements. Through the clients own impact analysis and risk assessment procedures, the outcome could be that redundancy at the fi le server level or instrument level is required.

Redundancy at the fi le server level means an additional fi le server (ie, if the primary fi le server fails the hot standby fi le server should automatically start), Figure 4 shows a typical cluster server arrangement. There are various means of setting up this arrangement, some more costly than others. This will require discussion with the client and selected BMS contractor on what options are available and what the likely risks are, Another option would be to look at the buffering capacity at the BMS panel CPU, By agreeing the trending requirements for each type of cGMP area environmental instrument (ie, Temp/RH - 15 minutes, Pressure - 1 minute), the BMS CPU could store up to 3-4 days worth of Information. When the server failure issue is resolved, the Information can be uploaded from the BMS panel CPU’s to the server for archiving.

Tagging Although tagging of instruments may look quite simple at a glance, it is imperative that the correct tagging standard is agreed with the client at the very beginning of AF&ID and design documentation development. If the tagging standard is not agreed, the re-work of AF&ID’s due to tagging errors can be costly and time-consuming. Where possible, the Instrumentation Systems and Automation society (ISA) standard should be used.

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Rys 3.

Transmitter signal repeated to a dedicated EMS

Hardwired Interlocks The interlocks between the BMS and the electrical drives for HVAC equipment also require detailed attention during the design phase (ie, frost stats, fi re alarm, damper open end switch interlocks). Other interlocks are low/high pressure switches (PSL or PSH) which should be installed if installations of smoke dampers are present, or if it is a VAVtype o f system. All interlocks between the HVAC equipment and the fan VFD/DOL electrical schematics need to be coordinated so that the required hardwired signals and voltages between VFD/MCC/BMS panels are maintained.

BMS Panels & Servers It is good practice to have a dedicated panel per AHU system. This ensures that all code and graphics generated are specific for this AHU only. It also helps during commissioning to be able to test specific AHUs in isolation, so that all necessary paperwork (IQ, OQ, PQ) can be reviewed and signed-off on a system per system basis.

All BMS panels, fi le servers and OWS should be on UPS power so that the BMS can keep trending of environmental parameters in the event of power failure. Server and OWS specifications should be reviewed and approved by the clients IT department. Spare capacity in the form of space for the installation of extra I/O should be provided per each BMS panel (ie, 20% is an average limit). This means additional installed rack space, bus rails, cable gland holes, power distribution etc.

High Level Interfaces With Client Site Historian & Vendor Equipment Any high-level interfaces to other control systems should be reviewed at a very early stage of the design to ensure that the selected interface protocol will function effi ciently and reliably, Commonly-available, download *.pdf version:

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multiple-sourced, networking components and protocols should be used to allow the BMS to co-exist with other networking applications, eg, interface between VFD and BMS via the commonly-used modbus protocol.

It is common for the BMS to send Information to the clients site historian for long-term storage of data. Any testing of interfaces off-site is recommended to avoid delays in the commissioning program on site and for the overall reliability of the interface.

Philosophy Of Alarm Management

Rys 4.

The principle of alarm Typical cluster server arrangement notification to operator/ maintenance personnel should be reviewed. A site philosophy should be agreed on how criTrainee testing and certification must also be available. tical plant alarms are dealt with on a daily basis, Most BMS All systems must be covered, especially in relation to system back-up procedures and data recovery, systems have various ways of sending alarms to operator/ maintenance personnel, ie, paging and email, Level of alarming — Level 0; Critical; Level 1; Urgent — should also be reviewed and agreed by the client so that the alarm most critical to the process gets acted upon fi rst. Again most BMS systems have various alarming levels which can be configured to suit the clients requirements.

Instrumentation All cGMP Instruments should be factory-calibrated and able to be calibrated on site by an instrument technician without reference to the manufacturer. Signal operation should be 4-20mA. All cGMP Instruments should be supplied with a factory-calibration certifi cate, The only exception to this requirement should be noncGMP areas. However, non-cGMP sensors should be good quality commercial grade type and signal operation can be 0-10V. All calibration equipment must be traceable to a National Metrology Institute such as NIST, NML or NPL. All Instruments should come to site pre-tagged. A sample tag should be submitted by the BMS contractor for approval prior to proceeding with tagging of Instruments. The BMS contractor should also identify the correct location for each instrument in their supply, Delivery of the Instruments to site should be on a JustIn-Time (JIT) basis to avoid misplacement by the installation contractors. The BMS contractor should also be responsible to ensure that all Instruments under their supply are installed correctly during their own walk-down procedures.

Training All training courses should be customised to meet the client’s requirement. Programs should include lecture, demonstration, hands-on practice and training manual.

Conclusion From the outset of the design, the BMS engineer needs to understand the clients requirements for the BMS system.

By identifying the design criteria for the BMS, the URS/SOW document can be generated to capture the clients BMS requirements. Covering the above topics with the client will help to ensure that the correct BMS system is selected to satisfy the URS. In addition, understanding the clients requirements will also feed back into the development of the HVAC AF&ID, electrical design, instrumentation selection, C&Q protocols and BMS contract procurement.

References (1) Project Management Group; (2) GAMP Guide for Validation of Automated Systems; (3) The Instrumentation Systems and Automation society (ISA).

Next month The development of the BMS SOO, network architecture drawings and IO list by the A&E fi rm will be discussed in the next issue of bs news, along with all the BMS contractors’ deliverables during their „Design/Build” and „Commissioning” phases,

Bibliography Oliver O’Reilly is a lead BMS Project Engineer with Project Management Group (PMG). A graduate of Dundalk IT Oliver has worked on a wide variety of projects from design, construction and commissioning in pharmaceutical and commercial Industries in Ireland and the UK.

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PAT

– how to achieve a good process?

Tomasz Demski, Mirosław Popieluch StatSoft Polska Sp. z o.o.

The Process Analytical Technology (PAT) strategy was designed by the FDA in August 2002, and was implemented by the European Regulatory Agency, the EMEA, in 2003. PAT is to form a scientifi c basis, using risk analysis, for designing, manufacturing and ensuring quality in the pharmaceutical industry.

I

n its recommendations to the industry FDA [1] presents the following definition of PAT: “Systems for analysing and managing production processes based on measures taken during the processes of critical parameters of quality, productivity characteristics and properties of the raw materials and materials during the process. The aim of using these is to ensure the appropriate quality of the product resulting from the completion of the process.”

In the traditional approach to quality assurance, applied before PAT’s introduction, management of the production process took place on the basis of recipes, and fulfi lment of the requirements by the final product was ensured by checking the product itself, in other words by acceptance inspection. This traditional approach is effective in delivering medicines of an appropriate quality, but it has the disadvantage of providing no back up or recommendations for improving the recipes, introducing innovations or widening knowledge about the processes.

The pharmaceutical industry’s role in health care and ensuring a high quality of life is exceptionally important, and this fact is refl ected in the enormous benefits which can be brought by improvements, the latest achievements in science and engineering and the most modern quality guarantee methods, if they are implemented in this field.

It is this fact which is the main motivation for PAT – to facilitate the introduction of innovation and encourage pharmaceutical enterprises to introduce innovations and new management strategies (often very well known and tried and tested in other branches of industry). The diagram below shows (in a slightly simplified manner) management using the traditional process. One point is worth noticing – after each stage the product is generally tested in a laboratory, and the results of these tests are available only after a long delay. Any indication that something needs to be changed in subsequent stages of production usually appears after the process is actually fi nished.

The diagram 2 shows the process after PAT is applied.

The key change is that we now take measurements directly during the process itself, and the results both of the measuring and their analysis so quickly that we can apply them in correcting the process. An important feature of PAT is the possibility of real time release (RTR) of batches. Here the way the measurements are taken should be noted – the most commonly used techniques are modern ones such as NIR, NMR and Raman spectroscopy, which enable us to obtain results very quickly, and effectively to observe the mixing process as it happens, thus allowing us to finish it at the appropriate moment.

Diagram 1

Diagram from program STATISTICA

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Diagram 2

Realising the PAT approach requires a system for collating measurements and making them available for analysis: PAT is based on data concerning the process and cannot be implemented without data. Also required are the appropriate tools for statistical data analysis, and both of these conditions are met by the STATISTICA Enterprise complex system. First of all, making use of the NIR spectroscope results requires advanced multi-dimensional techniques (main component analysis). Secondly, the processes occurring during the manufacture of medicines are often highly complicated and have many properties which need to be monitored by complex analytical tools such as multi-dimensional, multi-directional SPC, decision trees or neuron networks.

Apart from the scope of the statistical methods, another important aspect is the practical availability of the results of the analyses – these should be quickly and easily available so that those supervising the process can use them to make decisions.

It is worth mentioning PAT’s relation to another initiative concerning quality and innovation in the pharmaceutical industry - Quality by Design (QbD). We use QbD when designing a process or introducing changes to a project.

Thanks to QbD we find out how to apply PAT in the production phase: to which of the process’ properties, what is important, what we should be monitoring and what the acceptable parameter ranges are.

The major benefits from PAT are: • shortening the time of the production cycle, • avoiding rejects and repeat processing, • real time release, • automation: safety and fewer mistakes, • increased productivity, • control of variation.

Components of PAT The PAT system’s components can be divided into four groups: • Design • Measurements • Statistics • Control We will concentrate on two aspects – measurements and statistics.

I. Measurements Generally speaking, we have two types of measurements: • those concerning the course of the process, and gathered during it , and results of laboratory product tests

obtained after a certain phase of the process or production has fi nished.

As far as the data concerning the course of the process is concerned, we have two categories which differ according to their degree of complexity and method of application: • Measurements of such qualities of the process as temperature, pressure, substance flow, rotor speed, etc. In this case we are dealing with a relatively simple situation and a direct measurement of the quantity which concerns us.

• NIR, NMR and Raman spectra. Here we obtain a matrix of digits representing the spectrum, which requires a fairly complex statistical analysis (main component analysis) in order to interpret and make use of them.

This data, however, provides an invaluable opportunity to gain an insight into the process - we can find out, for example, if a mixture is homogeneous without conducting inconvenient, time-consuming and expensive laboratory tests.

Measurements can be taken: • At-line: samples taken from the production line and analysed nearby.

• On-line: samples taken and analysed outside the production line.

• In-line: sample tested on the production line.

II. Statistics With regard to the statistical layer, we make use of both one-dimensional (e.g. Shewhart control cards) and multidimensional techniques (all available in the STATISTICA programmes).

It is very important that the statistics directly support the implementation of the process, and this requires instant availability of the results of statistical analysis, which should be delivered “to the desk” of the person responsible for the process. Control may involve monitoring changes in key parameters (previously discovered using, for example, the QdB technique), and classic Shewhart control cards are most commonly used for this. In the case of complex processes, the number of such key parameters may be so high that a solution may be required which allows the use of, say, 100 control cards simultaneously (e.g. STATISTICA Monitoring and Alerting Server). Most often, however, monitoring will use multi-dimensional techniques adapted to the specific conditions of the pharmaceutical industry. Although these are complicated as far as calculations and concepts are concerned, from the user’s point of view they allow the trajectories of the process parameters to be followed in time (the figure 1 shows an example of such a monitor).

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Fig. 1 • Data analysis.

• Organisational changes.

• Validation of the solution.

We can use the results of the analysis for adjusting the process settings. These adjustments may affect previous stages of the process, in which case we refer to them as feedback, or subsequent stages of the process, when we call it feedforward.

Types of PAT Projects We can divide PAT projects into two classes depending on their main aim. The fi rst of these are projects aimed at discovering and understanding a process (strictly speaking the relations between the properties of the process, the raw material and the finished product). We normally have a lot of interconnected data, little of which have a signifi cant infl uence on the product quality. Ascertaining what is important, and what is not, is of great use. In addition we can discover the reasons for problems with the quality or productivity of processes.

The aim of a PAT may also be creating a model of a process, which will connect the parameters of the process with the qualities of the product obtained at the end of the process (or after one of its stages). We can use this process model to predict the results of the process, the process management or the optimisation of the process settings.

It is worth pointing out the connection between the aims of a PAT project and the current state of the process (see [2]). Thus, if we have a process worked out with which we are familiar and which has no problems with quality, the purpose of the PAT will be to improve its productivity.

In such a case we create a process model, then use this as the basis for optimising the process settings. In the case of processes which require quality improvement, the situation is different and the main aim of the PAT project is to eliminate problems with quality, and increasing productivity is a secondary consideration.

In turn, when dealing with new processes and products we start by applying experience planning (i.e. the QdB approach), and the QbD method is used in planning the process and when scaling up to the actual production.

In such cases we use mainly laboratory test results. The models can be used, for example, in optimising the stability of medicines produced.

The Course of a PAT Project A PAT project usually consists of the following stages: • Creating a measurement system.

• Integrating, harmonising and operating on data.

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In creating a measurement system it should be remembered that NIR spectroscopes (and other instruments of this type) should be checked carefully to ensure the appropriate quality of data and consistency of results based on spectral analysis. Such tests should be carried out not only at the start of the project (when installing and confi guring the spectroscopes), but regularly (e.g. every six months) while the measuring system is in use. NIR spectroscopy and the entire measuring system require calibration and precise checking.

As an example, if NIR spectroscopy involves tablets moving on a conveyor belt then it is worth checking whether the changing position of the tablets infl uences the results achieved. The results of such a test are presented in article [3].

It is worth noting that the creation of a measuring system is not confi ned to installing sensors, NIR spectroscopes, etc. A key element is the creation of a system for collating measurements and harmonising data from different sources, or the use of a specialised system which has been successfully applied to this purpose - STATISTICA Enterprise.

In the standard approach, we begin with a business analysis – by understanding data, the relationship between reality and the data which represents it. In other words, by precisely defi ning the process. We then collect past data concerning “good” and “bad” process cycles, and use this as the basis for creating a process model and assessing its effi ciency. Finally, we work out a way to apply this model to new batches of the product.

The fi rst PAT project carried out in any company does not have to be diffi cult – all it takes is a few reminders: • Choose a relatively simple, familiar process (or process stage) – don’t start from the hardest!

• The project should concern a process for which we have easily accessible data for a large number of batches.

• Don’t expect results too quickly – it is worth giving a PAT project enough time to show its usefulness.

• It requires the relevant tool for processing and synchronising data.

Literature • • •

•

PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance, document available on the FDA portal www.fda.gov.

Radspinner D., 2004, Implementing PAT – Industry Example, document available on the FDA portal www.fda.gov.

Cogdil R. P., Andreson C.A., Delgado-Lopez M., Molseed D., Chisholm R., Bolton R., Herkert T., Drennen J.K., 2005, Process Analytical Technology Case Study Part I: Feasibility Studies for Quantitative Near-Infrared Method Development, AAPS PharmSciTech 2005, 6 (2), www.aaspharmscitech.org.

Eames R., PAT Application using STATISTICA Enterprise, presentation available on the webpage www.statsoft.pl.

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3_2009_pl_en_spf.indd 27 für Polen mit altem Motiv.indd 1 Image Pharma 2009_englisch

2009-09-11 09:57:31 22:16:41 12.02.2009

production

Qualification Of Thermostatic Equipment In Pharmacy Martyna Gałka

Manager measuring laboratory POL-EKO-APARATURA sp.j.

The manufacturer of medicinal products is obliged to follow the requirements stipulated in the Health Minister’s Decree of December 3rd 2002 regarding Good Production Practices (Journal of Laws, December 21st 2002). This decree defi nes, among other things, the requirements concerning validation of the equipment used in producing medicinal substances such as human medicines, veterinary medicines, active substances, medical equipment, cosmetic products and biotechnological preparations.

V

alidation is intended to ensure that the defi ned method or process in which a device is used will, in a repeatable way, lead to results which fulfi l the defined acceptance criteria. Part of this validation process consists of qualifications – actions aimed at demonstrating and documenting that devices are correctly installed, they work properly and that using them brings about the expected results. Thermostatic devices used in pharmacy are also therefore subject to qualification. Validation of the process in which a thermostatic device is used should be preceded by drawing up a short validation plan.

Qualifications are divided into several stages: • IQ - installation qualification, • OQ – operational qualification, • PQ – process qualification.

Each stage is covered by documentation consisting of two parts: • a description of what is to be done and the acceptance criteria for each qualified parameter.

• a description of what was done and a final decision based on the results achieved in the tests conducted.

The user should provide the person conducting the qualification with information as to what applications the given thermostatic device will be put to, along with the criteria (mainly concerning temperature) it should meet. Disqualification of a device

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from one application does not mean disqualification in any other field (as, for example, other uses may require specialised limits within less demanding criteria).

Each stage of the qualification conducted should end with a decision as to whether or not it is acceptable (the next stage can commence as soon as the previous one has been accepted), and should also contain the conditions for conducting a re-qualification. Every technical intervention in the device, such as replacing the electronic controls, temperature sensor or heating/cooling elements, affects changes in its working characteristics, and is thus a factor requiring a new qualification to be conducted.

IQ – Installation Qualifi cation Installation qualification (IQ) is a documented verification stating that a device has been installed according to the specifications of its initial documentation, standards, principles and regulations (including the manufacturer’s instructions).

Installation qualification is conducted on new or modified equipment.

Installation qualification involves, at the very least: • checking and verifying the documentation supplied by the manufacturer (i.e. instructions for operation, use and maintenance), • a visual assessment of the device and verification that the product delivered, as well as its installation, is considownload *.pdf version:

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production

• •

stent with the technical specifications (including the manufacturer’s instructions), verification of construction materials, admission of the device into use.

In accordance with the protocol of the installation qualification, the tests and verifications should be documented and conclusions drawn from them. The IQ report should include information about the completeness of the documentation, the consistency of the qualification and a description of the observed deviations from the applicable criteria, which should result in corrective action.

OQ – Operational Qualifi cation Operational qualification (OQ) is a documented certification stating that the device is able to function in a repeatable manner in accordance with the user’s requirements, within limits defi ned in the initial documentation and specifications.

The aim of the operational qualification is to verify that a device works properly (in a repeatable way) within the fields of application stipulated in previous assumptions.

It applies to a device which has been installed and connected after installation qualification, and covers at the very least: • measurements and temperature tests planned according to the type of thermostatic device and its intended use.

• temperature tests conducted under conditions including the upper and lower limits of the scope of the device’s work, the so-called ‘worst case scenario’.

In the case of thermostatic devices, the operational qualification stage involves a range of temperature measurements being taken to verify the proper functioning of the device and its suitability for the processes intended and planned by the user. The assessment is made by measuring the average temperature reached by the device and the uniformity and stability of the temperature inside the chamber, and by checking the regulatory and measuring line. From a technical point of view, the temperature distribution test itself should be conducted using a multichannel temperature gauge with an assured measuring coherence, according to previously established methodology. The use of a multi-channel gauge allows the temperature to be measured simultaneously at many points in the usage space of the chamber.

PQ – Process Qualifi cation Exploitation qualification, also known as process qualification or PQ, is a documented verification stating that a device allows a repeatable result to be obtained (for example a temperature set by the manufacturer or user) in accordance with the stipulated specifications and assumptions. Exploitation qualification is conducted under the conditions in which a given device is actually used.

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Process qualification is conducted after the installation and operational qualifications have been successfully completed and passed. It involves, at the very least: • measuring the temperature range using a stand-in material which simulates the product used to fi ll the chamber of the thermostatic device.

• temperature range measurements carried out under conditions including the upper and lower limits of the device’s working conditions.

In some cases, process qualification may be conducted along with the operational qualification.

The end of the qualifi cation process The qualification protocol is prepared in written form and should be checked, confi rmed by both the person taking the measurements and the user, and should contain a description of the tests conducted and the acceptance criteria according to the requirements laid out by the user. The report should also contain a commentary to the deviations observed and the necessary conclusions with recommendations for necessary changes.

After the successful completion of each stage of the qualification, permission is issued in writing to conduct the next stage of qualification and validation. The available evidence confi rming and verifying the operational parameters and limits for the critical parameters of the devices used should be presented.

Choosing a qualifi cation provider Auditors who conduct reviews of the actions of a given institution within the pharmaceutical industry do not require accreditation for their activities in the units being tested (e.g. for temperature range). However, when choosing an external qualifier it is worth noting whether a given laboratory is accredited for calibrating thermostatic devices, and not just whether the thermometers used to take the measurements have been calibrated in an accredited laboratory. Accreditation issued by the Polish Centre for Accreditation is not just proof that a laboratory is competent and experienced in a given field, but above all a guarantee that the results obtained are reliable and that measurements are consistent, in other words they refer to the national standard for a given physical quantity (in the case of thermostatic devices – a unit of temperature).

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sponsored article

30

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2009-09-11 22:16:44

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production

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Special filling system for suspensions

Recirculation: Stop without any consequences Even short machine stoppages and interruptions can be problematic when dispensing suspension products. When restarting the line after a machine stop it was typical and inevitable to reject the first syringe tubs, since the intended product composition of solid or liquid components could not be guaranteed (suspensions can separate).

The recirculation technology of the Optima Group Pharma avoids this and furthermore provides a time saving. When restarting the line it is now possible to change directly into the “production mode” without product loss.

The filling and packaging line is equipped with a reaction path. The tubs, which are protected by plastic bags, are sanitized by means of alcohol and then enter the laminar flow zone. The Inova debagger and the Inova

Filling suspensions without any product loss, regardless of any stops.

Filling process of the filling and closing machine

TRR robot remove and dispose of the plastic bag and the Tyvek lid and liner. The Inova SV 125 is perfectly suited to be combined with these two upstream tub-handling machinery.

The whole syringe nest is lifted out of the tub and placed into the filling position. The syringes are then by means of the rotary piston pumps filled at five positions row by row.

Directly thereafter, the finished syringes are provided with a plunger rods that are fed from an automatic sorting bowl and positioned exactly in the syringe barrel. The nest with the filled and closed syringes are placed back into their original tub. The tubs are marked with batch data for product identity and tracking.

Here also the recirculation system waits to be activated: The high-precision recirculation valve is located directly in front of the filling needles. In case of an interruption in the filling and packaging process, even the smallest suspension quantities can be recirculated.

The specified, restricted sterile area, which has virtually been fitted into the line, was one of the challenges for this project. The smooth product flow, the clear arrangement of the line and compact dimensions complemented each other in an optimum way.

OPTIMA GROUP pharma GmbH Otto-Hahn-Str. 1, 74523 Schwäbisch Hall, Germany www.optima-group-pharma.com

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12.02.2009 10:02:06

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2009-09-11 22:16:46

Polish industry

A new subsidiary in Spain The value of the Spanish market for generic drugs is estimated at around €5 billion. This makes it the fourth largest pharmaceuticals market in Europe.

S

pain is the latest country where the Polish pharmaceuticals concern Adamed has decided to establish a presence by setting up a subsidiary company. The decision to enter the Spanish market follows an analysis of the attractiveness of that market and the medicines policy adopted there.

“Adamed’s entry into the Spanish market is an investment in the future. Poland is perceived by the Spanish as a good business partner. At present we employ 30 people in Spain, including 21 medical consultants. Our consultants’ network covers 95% of Spain and the Canary Islands.

Thanks to our programme of research on innovative therapies, investment in R&D, as well as manufacture and care for the quality of products, Adamed is building the trust of doctors, and thus also stimulating a huge amount of interest,” says Paweł Dąbrowski, Adamed’s Director for Foreign Subsidiaries.

Adamed has begun exporting its medicines to Spain.

The fi rst Adamed product which will be sold on the Spanish market is Acomicil, a modern medicine containing the active substance topiramate. Acomicil is a anticonvulsant, used chiefl y in the treatment of epilepsy. The drug has applications in both psychiatry and neurology. The value of the Spanish market for topiramate is estimated at more than €40 million.

“In the future we would like to build a twin company in Spain, with a significant product portfolio and extensive R&D activity. According to our plans, within one or two years Laboratorios Adamed could become a very impor-

32

tant element of the fi rm. The medicines introduced are an excellent platform on which we are building up a team and relations with people in medicine,” reports Paweł Dąbrowski, Adamed’s Director for Foreign Subsidiaries.

Another product being launched in Spain is Qudix (quetiapine), one of the newest medicines used in the treatment of acute and chronic psychiatric conditions.

The Spanish market for quetiapine is estimated at close to €61 million.

Adamed has still more products for treatment of the central nervous system which it plans to market in Spain.

“Development of the activity of our foreign subsidiaries in Spain and Ukraine, and increased export sales, make it necessary for us to increase our production capacity through planned acquisitions and the extension of plants in Poland,” adds Paweł Dąbrowski, Adamed’s Director for Foreign Subsidiaries.

In 2008, Adamed’s export sales totalled €7.2m, representing a rise of 52.7% over 2007. Projected revenue from sales abroad in 2009 is approximately €13m. In the next five years the company plans to increase its export revenue by more than €30m and to begin exporting to new countries.

At present Adamed’s exports, based on modern, mostly patented medicines, are sold to 15 countries: the Czech Republic, Slovakia, Hungary, Croatia, Spain, Portugal, Finland, Lithuania, Estonia, Turkey, Ukraine, Greece, Bosnia and Herzegovina, Albania and Kuwait.

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www.farmacom.com.pl

2009-09-11 22:16:47

sponsored article

– an example of product label evolution Comex

Polish industry

Pharmaceutical label During recent years we have witnessed dynamic changes in the packaging products market. The pharmaceutical industry is one of the key industry branches stimulating label manufacturing technology development, due to high requirements posed to the producers. Message, the main aspect of the label, due to legal requirements, marketing tendencies and evaluating conditions of competitive environment receives new, sophisticated form being a serious challenge for the printing industry.

Label –message carrier Pharmaceutical products, along with their packages, undergo extremely strict control conditions. Readability as well as factual and aesthetic conformity with registered package pattern, are the key issues related to pharmaceutical labels.

During recent years, the quantity of information that comes obligatory along with the product has multiplied, comprising different forms of presentation. The requirement to present essential amount of information on unchanged and limited package surface was fulfi lled by multilayered labels like peel&read or booklet.

Due to legal requirements imposed by European Community code – “The name of the medicinal product must also be expressed in Braille format on the packaging.”

Supplementary information printing in Braille code creates a new challenge for the label printers. The form and its readability have to be certified. In PPU “COMEX” Marburg Medium is the most frequent Braille standard being printed directly onto label, booklet or package.

turers. PPU “COMEX”, among others, offers seals (paper or holographic) to protect bottles, caps or card boxes.

Label – key element for product identifi cation and its monitoring in logistic chain PPU “COMEX” actively supports the development of label production techniques in both previously mentioned aspects – as an information carrier and protection element.

New concept of electronic product label combining both elements was elaborated. In similar way electronic passports contain RFID tags to identify the owner, electronic label named RFID.ON constitutes a key to the information on the product: its identifier, serial number, production date or recipient identifier. Electronic way of data encryption creates a new quality on the label market – being a key to a vast amount of information constitutes sophisticated and yet unknown counterfeiting protection. No need to say, all the aesthetic elements are preserved, at the same time.

Label – protection against counterfeiting.

Requirements related to product protection against counterfeiting form another group of challenges for the label manufacturers. Elements, commonly used for highly protected printings (banknotes, identity documents, visas etc.) are the new quality in the pharmaceutical packages market. First order protections (special inks, holograms) are commonly used. More and more frequently, however, higher protection orders (e.g. UV, IR inks, special holographic effects) are requested by pharmaceutical manufac-

Manufacturing of pharmaceutical label of 21st century – containing requested amount of information available in multiple forms and, at the same time, constituting a serious and solid barrier against the attempts of counterfeiting, forms a serious challenge for the printing industry. In PPU “COMEX” with new concept of electronic product label we make a significant step ahead.

download *.pdf version: www.farmacom.com.pl

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Polish industry

The privatization of Polfa Pabianice Robert Miller

Friday 24 July was the deadline for interested fi rms to submit bids to buy shares in the company Pabianickie Zakłady Farmaceutyczne Polfa SA (Polfa Pabianice).

privatization of the Polfa companies in Pabianice, Warsaw and Tarchomin, at a press conference. They are: • the Italian company Recordati Industria Chimica e Farmaceutica SpA; • Polfarmex SA; • Polpharma SA; • Adamed Sp z o.o.

T

he management board of Polski Holding Farmaceutyczny SA, together with its privatization advisers, began selecting a shortlist of bidders, and on 4 August 2009 made a decision as to which bids, out of the seven that PHF SA had received in response to the invitation sent to potential investors in Poland and abroad, would remain in the game.

Four fi rms were selected to proceed to the next stage of the privatization procedure. After making an examination of the company’s books under a due diligence process, these bidders will submit final purchase offers.

The deadline for submission of bids has been set by PHF SA (which currently holds 90% of Polfa Pabianice shares) at 15 October.

“We have selected the four best bids submitted by Polish fi rms and by an Italian investor,” said Artur Woźniak, PHF SA president responsible for the

34

Shortly, each of these fi rms will carry out a due diligence process, inspecting the fi nancial books. This will last until 26 September. Until mid-October we will be waiting for binding offers for the purchase of Polfa Pabianice. After we receive them, we will begin fi nal negotiations leading to selection of an investor. We are sure that by the end of the year we will have signed a contract for the sale of Polfa Pabianice,” said PHF SA president Artur Woźniak. “In the fi nal choice of investor we will be guided by several criteria. Apart from the proposed purchase price, these will also include the plant development plan that will be presented to us, and stability of employment.”

The heads of PHF and Polfa Pabianice view each of the investors as interesting for the company, because it is possible to expect either a synergy effect or significant product complementation. At present the plant specializes in producing generic medicines for cardiology, psychiatry and contraception. It is also developing its painkillers and rheumatism drugs, as well as working in cooperation with a foreign fi rm on the development and launch of an “interesting substance” which may bring in large amounts of revenue.

The president of PHF further announced that by the end of the year, a decision should also be made on the fate and method of privatization of two other companies making up the group: Polfa Warsaw and Polfa Tarchomin. download *.pdf version:

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The second company to be sold will be Polfa Warsaw, where the advisers are completing their work.

The management board of PHF expects to send invitations to potential investors as early as September. In the last quarter of the year the holding company will begin seeking purchasers for Polfa Tarchomin, the largest of the companies (the one which was originally planned to be the fi rst Polfa fi rm to be privatized).

PHARMA & BIOTECH TURNKEY PROCESS SOLUTIONS

Notes on the investors selected by PHF SA for the next stage of the privatization process: 1. Recordati Industria Chimica e Farmaceutica SpA Recordati Industria Chimica e Farmaceutica SpA is the parent company of the Recordati Group, a European pharmaceuticals group listed on the Italian stock exchange, engaged in research, development, manufacturing and sales of pharmaceuticals and pharmaceutical chemicals. It has its headquarters in Milan, Italy, and has subsidiaries operating in Belgium, the Czech Republic, France, Greece, Spain, Ireland, Germany, Portugal, Russia and the CIS, Slovakia, the US, Switzerland, Sweden, Turkey, the UK and the United Arab Emirates.

2. Polfarmex SA Polfarmex SA is a developing Polish-owned pharmaceuticals company. Polfarmex was founded in 1989, and was converted into SA (spółka akcyjna) form in 2001.

Its core activity is the manufacture of pharmaceutical substances for use in human therapy. It also produces and sells pharmaceutical semiproducts for the manufacture of products in the pharmaceuticals and chemicals industries, particularly calcium salts for pharmaceutical, veterinary, chemical and food production.

3. Zakłady Farmaceutyczne Polpharma SA Polpharma SA Pharmaceutical Works is the largest Polish manufacturer of generic drugs and pharmaceutical substances, specializing in the production of medicines for cardiology, gastroenterology and neurology, for prescription and for use in inpatient treatment. The company also produces a wide range of over-the-counter medicines.

Polpharma SA was created on 1 December 1995 as a result of the transformation of Polfa’s Pharmaceutical Works in Starogard.

4. Adamed Sp. z o.o.

Adamed Sp. z o.o. has been operating in Poland for 23 years. Its activity involves developing, promoting and selling, in Poland and abroad, latest-generation medicines for the most common civilization-related diseases.

Adamed asserts itself to be the largest Polish-registered pharmaceutical company to be exclusively Polishowned.

Source: http://www.phfsa.pl, Rynek Zdrowia, Gazeta Prawna, Parkiet, Puls Biznesu, Rzeczpospolita.

3_2009_pl_en_spf.indd 35

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2009-09-11 22:16:52

sponsored article

Polish industry

Patent protection of pharmaceutical inventions Magdalena Tagowska, PhD Patent Attorney, Patpol

Protection of industrial property, including patent protection, is one of the pillars of innovation-based economy and plays a key role in development of new technologies.

In recent years the patent protection system in Poland has evolved rendering effective protection of inventions in the most dynamically developing fi elds of technology, including pharmaceutical inventions.

I

n 1993 it became possible to obtain patent protection directly

for chemical compounds and pharmaceutical products as a

•

Pharmaceutical compositions, preparations and dosage forms;

•

Biological material comprising genetic information and

result of amendment to the former patent act – Act of October

capable of self reproduction or reproduction in a biologi-

19, 1972 on Inventive Activity (consolidated text in the Journal

cal system (e.g. genes, gene constructs, proteins, cell lines,

of Laws of 1993, No 26, item 117 with later amendments). It was

microorganisms, such as bacteria, fungi and viruses) and methods by means of which they are produced and used;

a breakthrough in protection of pharmaceutical inventions in Poland, as before patent protection of active substances was

•

re (e.g. a method of chemical synthesis), which extended over

Processes of manufacturing of chemical compounds and pharmaceutical products;

possible only through protecting a method of their manufactu•

First medical use (i.e. medical use of a compound used

a product obtained directly via that method. The subsequent

in the prior art for different purposes) and second and

amendments that provided even more complete protection

subsequent medical uses (i.e. novel use of a compound

for inventions in the field of pharmaceutics were as follows:

previously used for medical purposes).

•

Creating a possibility of granting patent protection for the use of already known substances, as well as for the use of

granted for methods of treatment of humans and animals by

for a new use; such possibility was formally introduced into

surgery or therapy, or diagnostic methods applied to humans

the present patent regulations – Act of June 30, 2000 In-

and animals.

dustrial Property Law (Journal of Laws of 2003, No 119, item •

•

It should be emphasized that patent protection cannot be

known substances for the purpose of obtaining a product

A party obtaining a patent is granted the exclusive right to

1117 with later amendments);

exploit the invention, for profit or professional purposes, for a

Implementation in 2002 of Directive 98/44/EC of the Euro-

20-year term counted from the date of filing the patent appli-

pean Parliament and the Council on legal protection of

cation with the Patent Office. However, the rights conferred by

biotechnological inventions (i.e. biological material based

a patent are limited in a specific way. Namely, it is possible to

inventions);

use a patented invention for recognition purposes, in particular

Entry into force of Council Regulation (EEC) No 1768/92

employing such an invention for research and experimental

concerning supplementary protection certificate for

purposes, for the evaluation thereof, analysis or teaching. The

medicinal products (SPC) upon Poland’s accession to the

particularly important limitation of rights conferred by a patent

European Union; this regulation enables „extension” of the

with respect to a pharmaceutical invention is a possibility of

20-year patent protection term by up to 5 years, and in

using the patented inventions to an extent necessary for obta-

case of medicinal products, for which clinical trials were

ining marketing authorization. Moreover, preparation of

performed involving pediatric population – even by up

a medicine in a pharmacy based on a physician’s prescription

to 5 and a half years.

is not considered as patent infringement.

Patent protection to inventions in the field of pharmaceu-

which has been fully adapted to the legislation of the Euro-

The present system of patent protection in Poland, tics (products, methods and uses) can be granted if they meet

pean Union, ensures complete and effective protection of

the general patentability criteria, i.e. they are novel (they do

inventions in the pharmaceutical field.

not form a part of the prior art), involve an inventive step (they are not obvious for a person skilled in the art), and are susceptible of industrial application in any kind of industry or agriculture. The following pharmaceutical inventions can be patented: •

Chemical compounds as such, as well as any of their forms, isomers, salts, prodrugs, metabolites, and even physical forms (e.g. crystaline forms, including polymorphs);

36

Patpol 162J, Nowoursynowska Str., 02-776 Warsaw P.O. Box 168, 00-950 Warsaw www.patpol.com.pl magdalena.tagowska@patpol.com.pl patpol@patpol.com.pl tel. +48 22 644 9657, +48 22 644 9659 fax +48 22 644 4402, +48 22 644 9600 download *.pdf version:

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Polish industry

Euroregional Pharmacy Centrum

Professor Elżbieta Skrzydlewska, PhD Dean of Faculty of Pharmacy

The problem with Polish pharmacy, especially with regard to creating a highly specialised workforce and implementing modern technology, are the result of long-term neglect in investment in this fi eld. Gaps in the system of monitoring and using new medicines are also due to inadequacies in the analytical back-up behind pharmaceutical analysis.

Y

ears of work on adapting the Polish legal and organisational systems to EU standards with regard to pharmaceutical law have now finished. This has been based on concern for the future of pharmacy as expressed by a desire to conform to the norms of the EU and the Accreditation Commission, and society’s expectations concerning: • highly specialised education of students • expanding the range of education open to students by new specialised pharmaceutical study areas (e.g. food analysis, cosmetology)

• •

•

conducting highly specialised courses for post-graduate pharmacists conducting scientific and service activities in highly specialised laboratories for the requirements of the food and agriculture, pharmaceutical and other industries. creating the conditions for didactic and scientific cooperation between EU states, “Eastern Bloc” states and Poland.

download *.pdf version: www.farmacom.com.pl

3_2009_pl_en_spf.indd 37

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Polish industry

38

We have been successful with regard to our common front with the Committee for Harmonising the Principles Regulating the Pharmaceutical Profession in Poland with EU Legislation. An important phase in the work of the Bureau for Recognising International Qualifications and Exchanges, on the syllabus requirements constituting the standard defining the equivalence of degrees awarded by various European colleges and universities for the same study area, has been completed.

The priority is now to fulfil the relevant directives of the European Parliament and the EU Council concerning undergraduate and post-graduate education.

EU law in this field is based on the demand for highly specialised laboratory services in the field of environmental protection, analysis of food and crops, and analysis of pharmaceutical and medical materials. To be effective, however, these actions require several stages of work.

The first stage is the creation of a didactic and scientific/ technical base meeting European standards, and the formation of apparatus to back up educational and scientific tasks, which will enable specialists to be educated to staff a modern economy, and ensure them continuous development through constant specialised training. For this reason, the authorities of the Medical Academy in Białystok have taken steps to create an ultra-modern scientific and educational unit – the Euroregional Pharmacy Centrum. In 2006, a preliminary application was submitted for financing the “Creation of a Modern Scientific and Educational Unit for the Requirements of the Euroregional Pharmacy Centre in Białystok” as part of the Operational Programme for the Development of Eastern Poland 2007-2013. In October 2007, this project was included on the Regional Development Ministry’s list of key projects. In March 2007 a preliminary agreement was signed with PARP, an intermediary institution, setting the level of European Union subsidies at 12,300,000 PLN, and the initial tasks were begun, consisting of preparing ideas and the building project. This resulted in the final application for funding being submitted to PARP in March 2009. This was confirmed and on July 28th 2009 an agreement was signed with PARP to subsidise it to the tune of 54.74m PLN. We turned out to have luck. Owing to the high value of the euro, the entire building will be financed from EU funds. The proper preparation of the idea and design, and of the application demanded a great deal of commitment from the Academy’s authorities and the Pharmaceutical Department, but it was worth it.

The money obtained from the EU will give the Podlasie region a scientific and educational Euroregional Pharmacy Centrum at Białystok Medical University, equipped with basic and specialised technical infrastructure. As part of this project, construction of a four storey building is planned – a scientific and educational centre called the Euroregional Pharmacy Centrum at Białystok Medical University, and will be physically connected to the existing Collegium Universum building. The new building will house the University’s Pharmacy Department, and four sections will have teaching areas there, so the Pharmacy Centre will contain two lecture theatres, seminary rooms (including a computer room), student laboratories, specialist scientific workshops, a training pharmacy, a dean’s office and storage and technical facilities with a total area of 8,013.46 m2. The building will be fitted with

specialist apparatus for educational and scientific purposes.

There are also plans to equip it with ICT (multimedia, wireless internet, a local computer system, server point, IT building management). The Pharmacy Centre’s surroundings will also be covered, and new access roads will be built to the building, and parking areas, pavements and green areas will be constructed around it.

It should be remembered that the project concerns the Pharmaceutical Department with the Laboratory Medicine Department of Białystok Medical University, which was founded as early as 1977. In 1999 it acquired the modern educational and scientific base necessary to develop the medical analysis study field. It does not, however, have its own specialist premises which would be required to further expand the study of pharmacy. The Pharmaceutical Department, though, has a large scientific and teaching staff (over 100 academic teachers, including 14 professors and 17 habilitated doctors). The Department’s achievements in the field of staff training and the scientific achievements of employees have entitled it to award medical doctor degrees for medical biology, as well as the title of habilitated doctor in medical biology.

The Pharmaceutical Department of Białystok Medical University is currently the only institution in the north-eastern macro-region of Poland with a concentration of outstanding specialists in the fields of pharmacy, chemistry and medicine.

These form the personnel base for the Euroregional Pharmaceutical Centre which will contribute not only to the development of the Department, but also to meeting the civilizational challenges faced by the north-eastern Poland macro-region, which is situated on the periphery of the European Union. The Department’s structures possess enormous scientific potential and collaborate extensively with other units of Białystok Medical University, as well as with other colleges and universities in the Podlasie and other regions of Poland. International collaboration is flourishing in the Pharmaceutical Department independent of the co-operation within Poland, with neighbouring countries (Lithuania, Belarus, Latvia and Ukraine), Western European countries (Germany, Turkey, France, Italy and Britain) and the USA (the National Cancer Institute in Frederic, Laboratory of Comparative Carcinogenesis) and Japan. However, in order to maintain partnership and scientific co-operation, constant development of the material base is required, which must be adequate for technological progress in the various fields of analysis and surveying. The wide range of methodological possibilities ensured by the Centre’s facilities make it the subject of interest from many scientific institutions in Białystok and Poland.

The project’s general aim is to prepare the University to play an active role in creating a competitive economy, and especially guaranteeing the Pharmaceutical Department with the Białystok Medical University’s Laboratory Medicine Department a high position in the world of education and science.

This aim will be achieved by creating a modern educational and scientific infrastructure, consisting of the four-storey building of the Euroregional Pharmaceutical Centre of Białystok Medical University, containing modern scientific, administrative and teaching facilities, as well as being equipped for science and education at a European standard. download *.pdf version:

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Specific aims include: • improving the quality of education by ensuring the students and teaching staff modern laboratory and teaching facilities with the appropriate equipment, • ensuring modern educational methods by equipping the building with wireless internet, and the new lecture theatres and seminar rooms with multimedia facilities, and creating computer rooms, • the opportunity to prepare students practically to carry out the profession of pharmacist, as employees of both chemists and the pharmaceutical industry, by creating a training pharmacy and properly preparing them in terms of workshops and facilities, • enabling the expansion and creation of new fields of study in the Pharmaceutical Department, • guaranteeing the quantity and quality of education of pharmacists appropriate to the demands of the market and the needs of society, • meeting the educational standards resulting from directives of the European Parliament and the EU Council, as well as the legal requirements for undergraduate and post-graduate education, • enabling highly specialised post-graduate education (both continuous and specialist) based on the Pharmaceutical Department, • allowing integration of pharmaceutical circles, both student and professional, from the whole macro-region, by the creation of auditoria seating 400 students, • the creation of modern science laboratories will make it possible to be accredited as part of the GLP, • an increase in the amount of scientific research conducted in the Department, while maintaining the high standard of work carried out, by modernising the equipment base and facilities of individual areas of the Department, • the opportunity to develop international collaboration in the field of highly advanced technology, • the development of co-operation in the economic field with, for example, medical institutions from the Podlasie region, the Border Guard, Fire Brigade, Police and Procurators.

The project is aimed mainly at benefitting students, university employees, pharmacists and medical analysts from the Podlasie region taking part in training, conferences, continuing and specialist post-graduate education, and the inhabitants of the region – patients and pharmacy customers.

The Pharmacy Centre will form an integral scientific and educational part of Białystok Medical University, which is why it will operate thanks to the Health Ministry’s educational funds and scientific funding from the Ministry of Science and Further Education. Taking into account the current scientific level of the Department and its potential for development under new technical conditions, we are counting on international co-operation and funding from EU programmes.

We took European Union standards as the basis for preparing the Pharmacy Centre, both in the field of student education conditions and standards for scientific work. The latter particularly concerns the accreditation requirements placed on technical preparation and facilities of individual scientific workshops. As regards the improvement of conditions for student education, it is particularly worth pointing out the training pharmacy project which has been prepared, and which meets the requirements laid down by the Pharmaceutical Inspectorate. The modern training pharmacy also enables students to be prepared for working directly with patients, especially with regard to pharmaceutical care which was introduced into the teaching syllabus of our University last year.

Polish industry

The direct aim of the project is to prepare the University to play an active role in creating a competitive economy, and especially guaranteeing the Pharmaceutical Department with the Białystok Medical University’s Laboratory Medicine Department a high position in the world of education and science. This aim will be achieved by creating a modern educational infrastructure as part of the project, which will serve to conduct the university’s activities to a higher standard, and to adapt the range of education offered by the Department to the current and forecast requirements of the labour market in Poland.

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The realisation of this project will help the Podlasie region to quickly level out inter-regional economic differences by creating an attractive place to study, increasing the number of students and consequently expanding the city’s infrastructure.

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Polish industry

ONCO - 3CLA Adamed has obtained approval from the Minister of Science and Higher Education for subsidization of a project called “ONCO-3CLA – A Targeted Biotechnological Anti-Cancer Medicine.” The subsidy agreement provides for support totalling 31 million zloty.

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he subsidy agreement signed by the Minister of Science and Higher Education for the “ONCO-3CLA – A Targeted Biotechnological Anti-Cancer Medicine” project concludes two-and-a-half years of efforts on the part of Adamed to obtain financing for the research. The fi rst part of the work involved obtaining key project status under the “Innovative Economy” Operational Programme. The next stage involved a series of verifications and the preparation of an application document that met all formal and substancerelated standards.

“The signing of the agreement by the Ministry of Science of Higher Education is a signal to us that we are moving in the right direction. This type of distinction reinforces our belief that research work on the “ONCO-3CLA – A Targeted Biotechnological Anti-Cancer Medicine” project will make a real impact on the world market for medicines,” said Małgorzata Korpusik, Adamed’s Director for Research, Development and Production.

For Polish pharmaceutical companies, our key task at the moment is to become part of the current of innovative development. Investment in programmes that develop advanced technologies should lead to significant improvement in the condition of the Polish economy and the state of the country’s industry. In the future we intend to continue to use such significant

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resources for the development of our companies and take an active part in further programmes being implemented by the Ministry of Science and Higher Education, said Małgorzata Korpusik, Adamed’s Director for Research, Development and Production.

As much as 85% of the amount of the subsidy allocated for research under the “ONCO-3CLA – A Targeted Biotechnological Anti-Cancer Medicine” project comes from the European Regional Development Fund (European Union resources), with 15% coming from the national budget. The project will be financed under Measure 1.4 (“Support for Specific-Purpose Projects”) of the “Innovative Economy” Operational Programme.

Implementation of the “ONCO-3CLA – A Targeted Biotechnological Anti-Cancer Medicine” project will constitute a breakthrough in world medicine. The involvement of key scientific institutions in the project creates an enormous chance for the development of an innovative therapy to fight cancer.

In targeted anti-cancer therapies, the therapeutic molecule is directed to the place where the cancer is present, and destroys only the cancerous cells, leaving the body’s healthy tissue intact. We believe that our hard work, supported by funding for the research, will end in success, and that we will be in a position to fight cancer effectively, said Małgorzata Korpusik, Adamed’s Director for Research, Development and Production.

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in China

Polish industry

Bioton i Bayer Schering Pharma Bioton SA and its Singaporean subsidiary SciGen have signed an agreement with Bayer Schering Pharma AG, granting it the right to distribute insulin on an exclusive basis in China . The deal is in line with Bioton’s strategic goal of international expansion in the sale of insulin through alliances with renowned pharmaceuticals companies in the world’s major markets.

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nder the agreement, worth €31 million payable up front, Bayer acquires the exclusive Chinese distribution rights to the insulin produced by Bioton under the SciLin ® brand. The agreement and advance payment guarantee Bayer the sole right to supply the Bioton product in China for the next 15 years.

Current research indicates that there are approximately 40 million patients receiving treatment for diabetes in China. The insulin market is the fastest-growing segment of the market for diabetes treatments in China, with a projected annual growth rate of more than 40%.

BIOTON SA, a company listed on the Warsaw Stock Exchange, is among the world leaders in the manufacture of recombinant human insulin, with registrations in the most attractive international markets.

www.bayerhealthcare.co.kr

Bayer is the leading inter national phar maceutical fi r m in China thanks to the success of Glucobay ® , our phar maceutical pro duct used to treat t ype 2 diabetes. Thanks to the planned distr ibution of SciLin ® we will continue to suppor t diabetes patients and strengthen our position in this growing mar ket, said Andreas Fibig, CEO of Bayer Scher ing Pharma AG.

Bioton’s strategy is based on: building a strong international position through sales of recombinant human insulin and other pharmaceutical products (1); carrying out research work on new clinically advanced products (including a third-generation vaccine for hepatitis B, and slow-release growth hormone) (2); and cooperation through strategic partnerships with leading world pharmaceutical concerns (3).

As well as expanding into Asian markets, Bioton already has an established position in Central and Eastern Europe and the markets of the Commonwealth of Independent States. The Bioton Group conducts research and development work at its centres in Switzerland, Finland, Israel and Poland.

The long-term cooperation agreement enables Bioton to realize one of its key strategic goals – the building of a strong international position for its insulin in growing markets by forming partnerships with leading pharmaceuticals companies. Thanks to the agreement we are reinforcing our position of leader in the manufacture of insulin, with such a renowned partner as Bayer, said Janusz R. Guy, President of Bioton SA.

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Polish industry

Celon Pharma joins the best

Monika Lamparska-Przybysz, PhD Mariusz Lewandowski

Celon Pharma, aPolish pharmaceutical company from Łomianki, a town near Warsaw, has just completed the next phase of studies (animal studies) associated with marketing new anti-tumour drugs for treating breast, prostate and colon cancer. If further stages of the study confi rm the effi cacy of using the drug in humans, this will be a total breakthrough in oncology. Our fi ndings indicate that using a Celon-modifi ed siRNA molecule, drugs can inhibit tumour growth in in vitro studies at a level comparable to cytotoxic chemotherapy. This means that over the next few years patients will be able to use the therapeutic method, which is considerably safer and less invasive than the ones used to date.

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hy has a domestic company decided to conduct such tough and expensive studies? The answer is simple: it is just these are biotechnology drugs which more and more often constitute a therapeutic basis for a number of signifi cant diseases. Despite the fact that these drugs are costly in terms of development and manufacture, they may be the only effective weapon in such serious diseases as neoplasms or neurodegenerative diseases. We have witnessed huge progress in biotechnology over the last few years. Since the 80s, research studies

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have focused on targets far beyond such simple proteins as insulin or growth factors. Monoclonal antibodies were introduced several years ago, although studies tend to use tools for genetic engineering procedures, such as RNA Interference.

The developmental strategy of our company is based on the assumption that within a few years we will become a key manufacturer of RNA Interference-modified oncology drugs in Poland. Studies confi rm their outstanding efficacy in the treatment of such major diseases as neopladownload *.pdf version:

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Polish industry

nucleic acid technology. – This makes our company clearly stand out in comparison with other domestic institutions or research laboratories. To date, nobody in the world has registered a drug based on this technology. We are among the global leaders with regard to these studies - asserts Monika Lamparska-Przybysz, PhD. Currently, 2nd and 3rd phase clinical studies on siRNA-based drugs are already being conducted in the world, however these medicinal products should not be expected in the market any earlier than in the years 2010-2012. At the end of 2010 Celon Pharma is also going to start the 1st phase of clinisms, Parkinson’s disease or AIDS said Maciej Wieczorek, the chairman of Celon Pharma company.

RNA interference was discovered a few years ago. It is a gene-silencing mechanism based on the complete inhibition of expression of particular proteins. This therapeutic approach is totally different from previous generations of drugs that exerted inhibitive effects on already synthesized proteins. RNAi is a technology dealing with the adaptation of a relatively recently described natural mechanism based on the use of tiny specific double strand RNA (dsRNA) fragments for selective silencing of expression for genes that constitute therapeutic targets.

To date, we have been successful in in vitro scale production of the drug and have managed to confi rm its efficacy in animals. Our results have been confi rmed in experiments using murine models with human cancers, including breast and lung cancers – said Monika Lamparska-Przybysz, PhD, head of R&D Laboratory for Celon Pharma Medicinal Products. – We have achieved a level of 50% tumour growth inhibition after siRNA administration when compared to a control (no inhibition). At the same time, we have not recorded any of the undesirable effects so characteristic of chemotherapy – she added. Currently, the toxicological and pharmacological studies necessary to get approval for launching the studies in human beings, are in progress.

Celon Pharma as the only company in Poland (in the world its competitors are, among others: Sirna Therapeutics, Alnylam Pharmaceuticals, Calando Pharmaceuticals) which conducts studies at the molecular level using cal trials studies for an anti-neoplastic drug based on siRNA technology.

Moreover, the company has started building a modern plant, in which mainly generic drugs will be manufactured. – By the end of this year we will possess approximately 1,200 square metres of modern research laboratories, in which 40 scientists of various specialties will be working, i.e. biologists, pharmacologists and pharmacists. This will be a full, integrated research platform – emphasizes Doctor Monika Lamparska-Przybysz.

In order to open the new laboratories, Celon Pharma has obtained EU fi nancial support for the implementation of two projects within download *.pdf version: www.farmacom.com.pl

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Polish industry

countries with a guarantee for the maintenance of the production quality standards in force.

Over the past few years the company has introduced into the market products from the following therapeutic groups: oncology (Aromek ® used in breast cancers), diseases of the nervous system (Donepex ® used in Alzheimer disease and Ketrel ® used in mentally disordered patients) as well as an anti-hypertensive drug called Valzek ®.

Over the coming years the company plans to broaden its product range by the introduction of modern drugs, with the use of its own innovative technologies in the scope of new therapeutic areas such as diseases of the respiratory system and circulatory system, cardiologic drugs, and intravenous sterile anti-neoplastic products. In its activities, the company considers care for patients’ health and its own authority as the basis for the quality policy applied, which is assumed as a primary goal in the company’s business matters. This is because the company’s market position depends mainly on the quality of its products. To achieve this, the GMP rules and Integrated Managing System (ISO: 9001, 14001 and 18001), which are necessary for quality assurance regarding drugs manufactured and scientifi c studies conducted, have been introduced.

Action 4.2: Operational Programme: Innovative Economy.

– The resources obtained will contribute to the faster implementation of Celon Pharma’s strategy regarding research and development of innovative drugs used in oncology and neurodegenerative diseases, among others, and within 2-3 years also to the formation of the R&D Centre as a part of the company – claims Maciej Wieczorek, company chairman.

Celon Pharma is an integrated biopharmaceutical company involved in the research, development, manufacture, sale and promotion of pharmaceutical products.

The company has its own R&D laboratories consisting of a Medical Chemistry Laboratory, Pharmaceutical Form Laboratory, Control and Quality Assurance Laboratory and R&D Laboratory for Biotechnological Medicinal Products.

The company can thus develop its own novel pharmaceutical technologies.

Furthermore, Celon Pharma owns a modern production plant, in which dry pharmaceutical forms (tablets) are produced. The manufacture of pharmaceutical products takes place in compliance with the GMP (Good Manufacturing Practice) quality system which has been implemented and is strictly observed, and thanks to which the fi rm has been issued a certifi cate of approval for the manufacture of its drugs by the Chief Pharmaceutical Inspector. On the basis of this GMP document, Celon Pharma can register and sell its drugs in all EU

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Since 2006 Celon Pharma has also run an R&D business in separate laboratories, i.e. the R&D Laboratory for Biotechnological Medicinal Products, Medicinal Product Formulation Laboratory and Medical Chemistry Laboratory. This activity concerns innovative biotechnology drugs based on the technologies of siRNA and small molecules weight compounds used in oncology and in metabolic and neurodegenerative diseases. R&D work is carried out by skilled employees who are totally dedicated to such activities and highlyexperienced in the life sciences and research relating to medical products. download *.pdf version:

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Polish industry

Extend the company’s factory in Ksawerów

Adamed has obtained permission to expand its factory in the Łódź Special Economic Zone (LSSE). The fi rm plans to spend 35 million zloty on extending its production plant and warehouse in Ksawerów. The expansion is motivated by the company’s need for increased production capacity.

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n 27 July 2009, the Provincial Offices in Łódź granted Adamed a permit to begin operations in the Łódź Special Economic Zone. Under the investment project it is planned to extend the company’s factory in Ksawerów. Work is currently under way on preparing the working plans.

Our increased export challenges, extensive portfolio of medicines and plans to introduce new production technologies have led us to the decision to increase production capacity at our site in Ksawerów, by building additional production and warehouse facilities said Małgorzata Korpusik, Adamed’s Director for Research and Development.

The Ksawerów site was opened in October 2001. Its core sections are the Solid Moulds Production Division, which manufactures cardiological and psychiatric medicines, and the Active Substances Production Division.

Due to our dynamic expansion in foreign markets and the large number of medicines expected to make up our portfolio in 2010–2015, we must significantly increase our production capacity in order to be able to implement the fi rm’s development plans effectively. Expansion of the factory, motivated by the need to increase production capacity, will enable Adamed to expand into world pharmaceutical markets, said Małgorzata Korpusik, Adamed’s Director for Research and Development..

We are interested in taking over the Polfa fi rms which are being privatized. The planned takeovers will directly lead to an increase in both our production capacity and our portfolio of medicines, as well as enabling us to expand our research and development activity, said Małgorzata Korpusik, Adamed’s Director for Research and Development.

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Polish industry

Avena Pharmaceutical laboratory “AVENA” was founded in April 1992 by Barbara Sokulska-Dura, Zofi a Palmowska and Włodzimierz Palmowski. From the beginning AVENA was a small civil law partnership and the production was run in a small area of the former preschool in Wyszyński street in Bydgoszcz. At the beginning, basic, essential tools in the production contained only few of equipment: mixing up agitator, slops, the funnel and the weight.

These inconveniences were offset by well-educated, experienced management and the commitment of the all employees. At this time, we were producing only 2 products.

For comparison, nowadays we produce about 30 medical products.

About company Gradually, with small steps the company grew in strength.

We increased the quantity of the equipment by purchasing containers, agitator, weights. We conducted repair works and modernization site, adapting the production to GMP requirements which came into force half of years 90. Our policy is competitive production and creating safety products with the highest quality. Our plant was developed by opening equipped quality control laboratory, strengthened with the qualified crew.

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Every year we released new products on the market, we invested in the production equipments, quality control assurance, employing more employees. It turned out that the further production in these conditions became impossible. We decided to find a new area for the new, modern manufactory plant. Finally AVENA announced an agreement to open a new manufactory plant in Osielsko, calm and clean county distant from Bydgoszcz of 15 km. New building construction started in 2003 and full production began in July 2005. One year later company converted into general partnership.

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AVENA Laboratory is conducting the nonsterile manufacturing, producing fluid, semisolid, and permanent forms with the different dosage (one dose, multidose) according to principles of the good manufactory practice (GMP), with the full care of the protection of the natural environment and for the broad development of employees. We also produce cosmetics in the little scope.

creative problems resolving. They use their skills in favour of the company successes. We continuously provide training programs to raise their professional qualifications and to improve manufacturing processes. Thanks to the application of the new technologies, modern devices and the first-class senior staff and production workers we manufacture high quality products. (according to GMP norms). Currently approximately 45 high qualified staff members are employed in the AVENA.

Short description of the company

Our successes

Pharmaceutical Laboratory AVENA - the general partnership, constitute one-storey, modern building of solid construction, an area of 1100,00 m2, in an area of 6200 m2 yard. located at the Leśna 42 street in Osielsko. The manufacturing comapany is located near the local route with the asphalt roadway.

It is important that the road traffic does not affect production processes. Area of the plant is fenced in and equipped with the gate. The company offers the large hardened yard, providing enough space for transport and parking place for employees and visitors. Approach to the company is guaranteed to the main road of the relation Bydgoszcz- Gdańsk, Szosa Gdańska street.

The high quality of our products was confirmed with the implementation of the GMP system - principles of the Good Manufactory Practice of the production as well as ISO9001÷2000 certification in 2007.

Our representative part of AVENA is the quality control assurance department – well equipped quality control and microbiology laboratory.

In the great scope we are using adequate social support provided by local government, cooperating with Council in recruiting of European Union’s means and with the Employment Agency in aspect of creating new refunded vacancies.

Recently our Company acquired Grants Program agreement to support implementation ISO9001÷2000 certification and creating four vacancies.

In August 2009 we applied for funds for modernization and improvement of the production process. At present, we have full-featured position for the production of ointment – the manufacturing process is entirely automatic.

Employees

Polish industry

Our products

Highly recommended products Glycerol suppository is our most popular product available for purchase in almost every pharmacy in Poland as well as abroad.

Information At all levels of the organization, AVENA staff is fully competent to carry out the tasks that fulfill their key accountabilities.

Education level and qualifications of the all staff members is our priority. Our management have an adequate scientific background, with a good knowledge of pharmaceutical production and appropriate experience. Moreover, they have ability of

AVENA product database offers detailed information about all of the AVENA products and their usage, complete with the respective contact address. All data is available regularly updated.

More information can be found at www.avena.com.pl

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conferences, fairs, training

BioForum 2009 Bio-Tech Consulting

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More then 800 participants – representatives from 10 countries, 60 exhibitors, presentation more then 80 R&D Projects, 230 biobusiness meetings (BioPartnering) - that are only some examples and effects this edition of Central European Forum of Biotechnology & Innovative BioEconomy – BioForum 2009 3-5 June, 2009.

Media Partner:

ioForum 2009 had many prestiguous atractions fields for participants this unique biobusiness event in the LifeScience and biotechnology-related sector: Biotechnology trade fair, exhibition, R&D poster presentations, prestigious seminars and workshops. Moreover during BioFourm 2009 there were many direct biobusiness meetings (BioPartnering) and Round Table Session. Organizer BioForum 2009 - Bio-Tech Consulting Ltd. Coorganizers this unique event were: The City of Lodz, The Lodz Voivodship and BioForum 2009 Partners: the keys institutions and companies from Central Europe in LifeScience and biotechnology-related sector, e.g.: • Hungarian Biotechnology Association (Hungary), • Tartu Biotechnology Park (Estonia), • ScanBalt BioRegion, • Lithuanian Innovation Centre (Lithuania), • Latvian Biotechnology Association (Latvia), • CzechBio (Czech Republic), • Wroclaw Research Center EIT+ (Poland), • Life Science Cluster Krakow (Poland) • The Steinbeis Network (Germany) BioForum was an excellent opportunity to recognise many actually achievements, mainly in biotechnology-related field and LifeScience. During BioForum 2009 was showed 60 exhibitors from Poland, Germany, Belgium, Lithuania, Latvia, Hangary and Czech Republic.

Trade fair part of BioForum 2009 was directed mainly to representatives of biosector, whose were interested in the new technologies and implementation of new solutions to their companies. The recipients this special part of BioForum were scientists from universities and institutions, also PhD’s and students from Poland and other Central European Countries. More then 800 participants - representatives from 10 countries were attendees BioForum 2009.

Exhibitors Bioforum 2009 were companies and institutions, which work in transfer technology field, patent offices, venture capital, seed capital,

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technology parks, technological advanced centers and technology incubators.

The unique part of Central European Forum of Biotechnology & Innovative BioEconomy – BioForum 2009 was presentation R&D projects, which have a potential for application e.g.: for health care, pharmacy and biotechnology.

This year on BioForum 2009 was a record-breaking number of presentations – more then 80 R&D projects. During poster presentation were presented R&D projects and scientific services from Poland and other Central European Countries.

Two days of BioForum 2009 (3-4 June) were dedicated to biotechnology-related seminars, presentations and workshops.

BioForum 2009 subjects were concentrated on such topics as e.g.: potential of biotechnology sector in Central European Region, aspects of commercialization, financial aspects of R&D projects, potential business partnership and possibility for cooperation in commercialization scientific research results.

BioForum 2009 – was the first edition this particular event for this Region of Europe - with BioPartnering – a special possibility to make an appointment for business meetings between attendees BioForum. It was an unique place, where more then 230 biobussiness meetings took place in LifeScience and biotechnology-related field.

Next edition of BioForum 2010 – Central European Forum of Biotechnology & Innovative BioEconomy – the most significant event for biosector of Central European Countries, will held in Poland, Lodz, 19-21 May, 2010. download *.pdf version:

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reports, projects, plans

Pharmaceutical biotechnology in Poland Sector to boom in 2011

Today the market of biotechnology that can be used in pharmaceutics and medicine (“red biotechnology”) is growing at a moderate pace in Poland. In 2008 sector players’ sales even declined as Bioton, the largest Polish biotech fi rm, performed poorly. Biotechnological fi rms are working intensely on new products whose sales will make a large impact on the pace of growth of the sector in two years.

Strong development of biotechnology not sooner than 2011 In the last two years the Polish pharmaceutical biotechnology sector in Poland has seen a significant decline in the annual pace of sales growth, according to the latest PMR Publications’ report “Biotechnological innovation in the pharmaceutical industry in Poland”. According to PMR Publications’ estimates, in 2008 the industry’s revenues fell as a consequence of the worse performance of the largest Polish biotech company Bioton. As a result, in 2008 biotech companies from the Polish pharmaceutical sector noted aggregate sales of an estimated PLN 607m (€173m), around 2% less than in 2007. Nevertheless, in future years, despite the worse economic situation, the market will grow at several percent a year while in 2011 sales should expand by almost 30% y-o-y. Such a jump will be the offspring of the development of innovative projects which today are in the seed and start-up stages are not yet yielding earnings.

EU funds power sector growth As elsewhere in the world, access to high risk financing is decisive to development of innovative technologies. The availability of EU funds in Poland has made it possible to support the development of investment firms interested in investing in risky ventures in the biotechnology sector. Innovative Economy Operational Programme is the most important of the accessible EU funds. Also, thanks to the right use of EU funds, today it is easier for companies active in Poland to finance investments in research and implementation of innovative technologies. In our opinion, despite the worse economic situation in the world, in the short term Poland has a chance of developing real biotechnological industry.

According to the Ministry of Economic Affairs, between 2007 and 2013 companies and scientific institutions from the medical, pharmaceutical and biotechnological sector will, thanks to EU funds, execute project with combined value of around PLN 662m or approx. €150m (Innovative Economy Operational

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Programme), out of which PLN 120m (approx. 27m) will be allocated to projects connected with the medical equipment and technologies sector and dietary supplements1.

Meanwhile, the decisive bulk of the remaining EU funds will be directly or indirectly linked with the red biotechnology sector in Poland. This figure is not fi nal as many tenders have not been fi nalised yet. Moreover, more competitions are to be announced in the next few months and years.

More and more innovative projects Although official statistics do not show a growth in the number of biotechnological companies in Poland, in fact their number has grown in recent years. For example, in 2007 two biotechnological companies, Mabion and Selvita, were established, and in 2008 one – Celther.

The fact that the Polish Life Sciences sector is only beginning to develop intensively is best illustrated by the number of new innovative ventures, especially from the biotechnology sector linked with the pharmaceutical industry. It is worthwhile to mention innovative projects carried out by such companies as: • Celther (stem cell therapy) • Celon Pharma (siRNA-based therapy) • Mabion (modified monoclonal antibody therapy) • Euroimplant (tissue engineering and regenerative medicine) • Biocontract (innovative vaccines against skin and kidney cancer).

The abovementioned fields – focus of today’s efforts of Polish firms, in the future will without a doubt be a source of a competitive edge for the Polish red biotechnology sector.

More information on biotechnology sector in the newest PMR Publications’ report “Biotechnological innovations in the pharmaceutical industry in Poland 2009”.

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Benefi ciary

Project

Total project value

Wroclawskie Centrum EIT+ Sp. z o.o.

Biotechnology and advanced medical technologies

PLN 105,678,073

Biotechnology and Antibiotics Institute

Biotechnology Centre of medical products. Package of innovative biopharmaceuticals for therapy and prophylactic care in humans and animals

PLN 89,739,098

University of Lodz

Role of transporters of multi-drug resistance in pharmacokinetics and toxicology - in-vitro tests in pharmaceutical and clinical practice

PLN 62,344,740

Jagiellonian University

Jagiellonian Centre for Drug Development

PLN 48,131,033

Lodz University of Technology, International Education Centre

Biodegradable fibrous products

PLN 35,962,041

Institute of Pharmacology at the Polish Academy of Sciences

Modernisation of building and research infrastructure of the Institute of Pharmacology at the Polish Academy of Sciences in Krakow with a view to setting up innovative scientific workshops for brain research

PLN 29,518,373

Jagiellonian University

Molecular biotechnology for health

PLN 28,830,757

ICHEM Research and Production Centre at the Lodz University of Technology

Implementation of innovative technology for the production of dietary supplements and functional foods

PLN 25,841,502

Institute of Basic Technology Problems at the Polish Academy of Sciences

Diagnostic ultrasound apparatus – new methods for diagnosis and imaging of tissue structure of human organs

PLN 22,640,000

Institute of Pharmaceuticals

Development of innovative technologies for ophthalmic drugs with special therapeutic and social importance

PLN 21,875,560

Institute of Pharmaceuticals

Innovative technologies of oncology drugs with special therapeutic and social importance

PLN 21,319,900

Institue of Electron Technology

Micro and nano-systems in chemistry and biomedical diagnostics

PLN 20,217,301

Medical University of Białystok

Development of method for discovery of markers showing a predisposition to the development of insulin resistance

PLN 20,011,919

JCI Venture

Initiating innovative activities within the framework of the Jagiellonian Park and Technology Incubator

PLN 17,776,118

Institute of Immunology and Experimental Therapy at the Polish Academy of Sciences (PAN)

Optimisation of characteristics and development of phage preparations for therapeutic purposes

PLN 13,660,000

Wroclaw Technology Park

Development of cooperative links of Nutribiomed cluster aimed at commercialisation of innovative solutions

PLN 13,138,380

Przedsiebiorstwo Produkcyjno-UslugowoHandlowe „MEDGAL” Józef Borowski

Development of production of innovative bone implants and instruments

PLN 11,666,800

Celon Pharma

Innovative oncology drug arresting the activeness of AP-1 transcription factor

PLN 11,341,459

Polymer and Carbon Materials Centre at the Polish Academy of Sciences

Temperature-controlled bio-compliant polymers as skin substitutes for treating burns and wounds

PLN 9,819,345

Institute of Pharmacology at the Polish Academy of Science

Allosteric modulation – new strategy in pharmacotherapy.

Identification of psychotropic properties of psychotropic ligand glutaminergic III flu receptors

PLN 8,551,895

Institute of Hearing Physiology and Pathology

Integrated IT System Supporting Research on Hearing Physiology and Pathology

PLN 8,106,492

Novasome Research and Development Center

Transformation of CBR Novasome into a R&D Centre

PLN 5,813,074

Medima

Medima’s new generation multi-module infusion system

PLN 5,468,031

Note: as on 30 June 2009; includes also research in the field of new medical technologies and medical equipment. Excluding typical IT projects, e.g. creation of internet

reports, projects, plans

Companies from the biopharmaceutical and related sectors, which have received the largest financing from the Innovative Economy Operational Programme and project value in Poland, 2009

portals about health and typical healthcare projects, e.g. construction of a healthcare centre. Only projects of value above PLN 5m.

Source: Ministry of Economic Affairs, 2009

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reports, projects, plans

Report on the situation in the pharmaceuticals industry Pigułka

More than 60% of the medicines sold in Poland are Polish-produced.

Nonetheless, domestic pharmaceuticals account for only about 40% of the Polish market when measured by value. There is a dynamic increase in exports of medicines produced by the Polish pharmaceuticals industry, but imports are growing signifi cantly faster.

L

ast year the total number of people employed by Polish pharmaceuticals fi rms was 23 995, an increase of 1.4% over the equivalent period of 2007. Total revenue was 13 220.8m PLN, which is 1350m PLN more than a year previously. The overall pre-tax profit from pharmaceuticals production was 1525.5m PLN, a rise of 29.8% over 2007; similarly the total net profit rose by 25.9% to reach 1281.6m PLN. Total debt of pharmaceuticals manufacturers in 2008 was 3305.9m PLN, 0.3% lower than in 2007. In 2008 there was a 9.8% improvement in employee productivity, to a figure of 502 000 PLN per employee. The value of capital expenditure on production in 2008 was 21.2% higher than in the equivalent period of 2007, reaching a final figure of 681.4m PLN.

The value of turnover in pharmaceutical products in 2008 was US$7766.3m. Compared to the equivalent period of 2007, this represented a rise of 39.0%, or $2180.7m in absolute terms. The trade balance is negative, at –$4461.5m. The value of imports, which significantly exceeds that of exports, stood at $6113.9m (a 35.2% increase). Exports, however, rose by 55.4% to total $1652.4m.

Source: Pigułka

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