25th – 27th October 2011

Chemical and Pharmaceutical Intermediates (CPhI) exhibition.

To be held at the Messe, Frankfurt, Germany.

For more information please visit:www.cphi.com/home

22 – 23 May 2012

International Contract Services Expo (ICSE), Philadelphia, USA.

For more information please visit:http://www.icsexpo.com/icse-usa

14th June 2012

Biotech Outsourcing Strategies CMC Sohuset Conference Centre, Scion DTU, Horsholm, Denmark.

For more information please visit:http://www.bio2bevents.com

www.tillotts.com

As we prepare for CPhI (October 25 - 27 at the Messe, Frankfurt), Europe’s premier CMO exhibition, we focus this edition of our newsletter on profiling the extensive range of manufacturing facilities available within the Zeria Group. Being part of a global and fully integrated healthcare company is a key requirement for many of our customers as they increasingly rely on proven manufacturing expertise and a global reach.

Our technology article profiles our newly acquired ‘TA.TX Plus’ instrument for texture analysis which has been cited as an area of interest by several of our customers.

The last few years have witnessed considerable change and turbulence within the global pharmaceutical industry as many large companies have sought to divest their manufacturing assets and non-core development activities and rely more on external Contract Manufacturing Organisations (CMOs). This has been primarily driven by a need to reduce costs as drug patents continue to expire and fewer blockbusters are emerging from pharmaceutical pipelines.

Tillotts Services has reacted to these changes through providing an increasing range of contract development and CMO services together with a responsive and customer-centric approach. Our contract research capabilities are aligned to help our customers’ “fast-track” their development candidates and expedite

registration and product approval. We regularly work with smaller biotechnology companies who typically operate a virtually integrated structure and come to rely on our ability to meet their needs and essentially become an extension of their R&D department. We achieve this by facilitating close interaction at the scientific and project management level and adopting a flexible approach as project needs and goals often change.

Our manufacturing customers tell us that they want to be reassured that they are working with an established, secure and global manufacturing expert who can anticipate their future needs. We are able to address challenges at all stages of the pharmaceutical life-cycle; so we can help customers identify new formulations for a clinical trial or help develop a market extension strategy through an improved dosage form.

Issue 3

Responding to new industry needs in times of change

NEWSLETTER

Acknowledgements: Design by David Anthony, AK Design (Scotland) Ltd.

For more information, please contact us at:

Q: So André please tell us a little about yourself?

A: I have lived in Basel since 1992, where I moved to directly after finishing my apprenticeship as a galenical technician. Within my previous roles, I have been employed as an Associate Scientist at Novartis (2005-2009) and as a Senior Formulation Scientist at Geistlich Pharma AG (2009-2011).

My hobbies are computers, travelling, hiking, reading and music.

Q: When did you join Tillotts?

A: I joined in June 2011 and have been busy working on new customer projects and applying our technologies which I have enjoyed.

Q: What is your function at Tillotts?

A: As a Formulation Scientist I am involved in developing new formulations at the lab scale that will be transferred to production. Our key objective is to fully understand the potential scale-up challenges and ensure that we have a robust process. I enjoy the challenge of finding solutions to problem drug development candidates and working within a dynamic team.

Q: What was the biggest challenge for you at Tillotts?

A: Managing several demanding projects which typically have tight deadlines.

Q: Which project are you most proud of?

A: Transferring a laboratory process to production scale is always exciting for a scientist since it provides a definitive test of how well you have done your job and anticipated potential issues. It is a proud moment when the hard work of our team comes together and our customers’ have their product on time and on budget.

Q: What will be your next bigger challenge at Tillotts?

A: Our in-house research that is focused on a new approach to poorly soluble APIs is currently presenting plenty of challenges, however we have made good progress and now plan to file a patent. Once established, it will deliver a lot of confidence for Tillotts Services and for our potential new customers.

In the previous issue of our Newsletter we interviewed Thomas Kaiser, who heads up our engineering group. In this issue Claudio Scialdone interviews a relatively new employee André Solioz who works within our formulation development team and is based at our Ziefen site.

ww

w.tillotts.com T: +41 61 935 28 28

F: +41 61 935 28 29E: services@tillotts.com

Tillotts Pharma AGTillotts ServicesHauptstrasse 274417 ZiefenSwitzerland

Tillotts Services will be represented at the following events during 2011 and 2012. We would be delighted to meet with you.

Let’s Have Coffee..

Going to CPhI this month? Registration is free

(http://www.cphi.com/visitors) and Frankfurt is an excellent venue for what is a mammoth show with previous visitors from over 125 countries.Tillotts Services will be located at Exhibition Stand 41F67 in Hall 4.1

so please come and visit us.

Copyright © Tillotts Pharma AG 2011 www.tillotts.com

Focus on TechnologyWithin this section we aim to profile a technology area related to our business.

We have recently purchased a new TA.TXPlus Texture Analyser from Stable Micro Systems®. This will be utilised in our formulation development laboratory for; (i) assessing the physical properties of semi-solid and/or liquid lipid-based formulations, and (ii) investigating the compatibility of lipid-based formulations with the capsule shell during early stage development and stability programmes. We now profile this technology and would be happy to address any specific questions.

Texture profile analysis is a useful tool for the qualitative and quantitative evaluation of possible changes in mechanical properties (stiffness, brittleness, tensile strength, adhesiveness, and others) of semisolids and liquid lipid-based formulations. The technique is also able to measure the effect of excipients on the integrity of hard shell capsules. For example, adhesiveness is a very important factor when developing formulations that should adhere to the mucosal membrane of the Gastro Intestinal Tract (GIT) (muco-adhesive formulations). Based on a broad range of applications of the technology for the development and stability assessment of lipid formulations, Tillotts decided to acquire this instrument. This is an important step for increasing our development capabilities for the assessment of liquid filled hard gelatin capsules. We can now therefore routinely test the stability and compatibility of the capsule shell with the formulation inside the capsule as well

as the effect of environmental conditions such as humidity. This technique is also helpful for measuring the adhesion strength of the coating formulations to the surface and for blister pack integrity. Principally, the apparatus is composed of an analytical probe moving towards or away from the sample (Figure 1). From plotting the resultant force against displacement/time several mechanical parameters may be defined (e.g. brittleness, stiffness, and adhesiveness, etc..).

Figure 2 shows the texture profile of two samples with different behaviours. By increasing the speed of the probe the force on the sample increases in a different manner depending on the sample elasticity or stiffness (slope of the linear region of the curve) until brittleness occurs. Sample 1 (blue) showed more elasticity (stiffness) than Sample 2 (red) which exhibited more plastic behaviour (higher softness). In the latter case, rupture occurred when the tensile force was reached.

Definitions of Some Mechanical parameters:

Brittleness/Softness = the force required to attain a given deformation.Elasticity/Stiffness = the work required to deform the product without being broken.Adhesiveness = the work necessary to overcome the attractive forces between the sample surface and the probe surface.

In late 2009 Tillotts Pharma AG became a wholly owned subsidiary of Zeria Pharmaceutical Co.,Ltd. Zeria strives to efficiently manufacture products based on the theme “promptly providing the required products at the time and the amount needed without delay”. In keeping with this spirit, Zeria has now established an optimal production infrastructure underpinned by a range of world-class manufacturing facilities that include; the Saitama Plant, the Tsukuba Plant and IONA INTERNATIONAL’s Fukushima Industrial Park, all located in Japan. Within Europe, Tillotts Services Ziefen Plant and Biofac Esbjerg’s Esbjerg Plant serve to complement an impressive and versatile range of manufacturing assets.

Production Capabilities within the Zeria Group

Ethical pharmaceuticals and OTC drugs (oral solid dosages, ophthalmic solutions, ointments, injections, etc.)

Pharmaceutical, designated quasi-drug and health-foods

Saitama Plant (Japan) Tsukuba Plant (Japan)

Cosmetics and quasi-drug products, etc.Sodium chondroitin sulphate

Biofac Esbjerg’s Esbjerg Plant (Denmark) IONA INTERNATIONAL’s Fukushima Industrial Park (Japan)

Figure 1The TA.XTPlus Texture Anayser

Figure 2Texture Profile Analysis

Displacement/Time

Forc

e

Stiffness

Brittleness

Rupture1

2

Tillotts Services Ziefen plant has been manufacturing liquid-filled capsules for over 26 years and our annual production volumes now exceed 150 million capsules per year. The facility operates to GMP and is routinely inspected by Swissmedic. Our continued expansion includes a newly refurbished and equipped formulation development laboratory for early stage pre-clinical and clinical development. We are also extending our coating technologies and equipment for both capsules and tablets.

Ziefen Plant – A Global Centre for Liquid-fill Encapsulation

Copyright © Tillotts Pharma AG 2011 www.tillotts.com

Focus on TechnologyWithin this section we aim to profile a technology area related to our business.

We have recently purchased a new TA.TXPlus Texture Analyser from Stable Micro Systems®. This will be utilised in our formulation development laboratory for; (i) assessing the physical properties of semi-solid and/or liquid lipid-based formulations, and (ii) investigating the compatibility of lipid-based formulations with the capsule shell during early stage development and stability programmes. We now profile this technology and would be happy to address any specific questions.

Texture profile analysis is a useful tool for the qualitative and quantitative evaluation of possible changes in mechanical properties (stiffness, brittleness, tensile strength, adhesiveness, and others) of semisolids and liquid lipid-based formulations. The technique is also able to measure the effect of excipients on the integrity of hard shell capsules. For example, adhesiveness is a very important factor when developing formulations that should adhere to the mucosal membrane of the Gastro Intestinal Tract (GIT) (muco-adhesive formulations). Based on a broad range of applications of the technology for the development and stability assessment of lipid formulations, Tillotts decided to acquire this instrument. This is an important step for increasing our development capabilities for the assessment of liquid filled hard gelatin capsules. We can now therefore routinely test the stability and compatibility of the capsule shell with the formulation inside the capsule as well

as the effect of environmental conditions such as humidity. This technique is also helpful for measuring the adhesion strength of the coating formulations to the surface and for blister pack integrity. Principally, the apparatus is composed of an analytical probe moving towards or away from the sample (Figure 1). From plotting the resultant force against displacement/time several mechanical parameters may be defined (e.g. brittleness, stiffness, and adhesiveness, etc..).

Figure 2 shows the texture profile of two samples with different behaviours. By increasing the speed of the probe the force on the sample increases in a different manner depending on the sample elasticity or stiffness (slope of the linear region of the curve) until brittleness occurs. Sample 1 (blue) showed more elasticity (stiffness) than Sample 2 (red) which exhibited more plastic behaviour (higher softness). In the latter case, rupture occurred when the tensile force was reached.

Definitions of Some Mechanical parameters:

Brittleness/Softness = the force required to attain a given deformation.Elasticity/Stiffness = the work required to deform the product without being broken.Adhesiveness = the work necessary to overcome the attractive forces between the sample surface and the probe surface.

In late 2009 Tillotts Pharma AG became a wholly owned subsidiary of Zeria Pharmaceutical Co.,Ltd. Zeria strives to efficiently manufacture products based on the theme “promptly providing the required products at the time and the amount needed without delay”. In keeping with this spirit, Zeria has now established an optimal production infrastructure underpinned by a range of world-class manufacturing facilities that include; the Saitama Plant, the Tsukuba Plant and IONA INTERNATIONAL’s Fukushima Industrial Park, all located in Japan. Within Europe, Tillotts Services Ziefen Plant and Biofac Esbjerg’s Esbjerg Plant serve to complement an impressive and versatile range of manufacturing assets.

Production Capabilities within the Zeria Group

Ethical pharmaceuticals and OTC drugs (oral solid dosages, ophthalmic solutions, ointments, injections, etc.)

Pharmaceutical, designated quasi-drug and health-foods

Saitama Plant (Japan) Tsukuba Plant (Japan)

Cosmetics and quasi-drug products, etc.Sodium chondroitin sulphate

Biofac Esbjerg’s Esbjerg Plant (Denmark) IONA INTERNATIONAL’s Fukushima Industrial Park (Japan)

Figure 1The TA.XTPlus Texture Anayser

Figure 2Texture Profile Analysis

Displacement/Time

Forc

e

Stiffness

Brittleness

Rupture1

2

Tillotts Services Ziefen plant has been manufacturing liquid-filled capsules for over 26 years and our annual production volumes now exceed 150 million capsules per year. The facility operates to GMP and is routinely inspected by Swissmedic. Our continued expansion includes a newly refurbished and equipped formulation development laboratory for early stage pre-clinical and clinical development. We are also extending our coating technologies and equipment for both capsules and tablets.

Ziefen Plant – A Global Centre for Liquid-fill Encapsulation

25th – 27th October 2011

Chemical and Pharmaceutical Intermediates (CPhI) exhibition.

To be held at the Messe, Frankfurt, Germany.

For more information please visit:www.cphi.com/home

22 – 23 May 2012

International Contract Services Expo (ICSE), Philadelphia, USA.

For more information please visit:http://www.icsexpo.com/icse-usa

14th June 2012

Biotech Outsourcing Strategies CMC Sohuset Conference Centre, Scion DTU, Horsholm, Denmark.

For more information please visit:http://www.bio2bevents.com

www.tillotts.com

As we prepare for CPhI (October 25 - 27 at the Messe, Frankfurt), Europe’s premier CMO exhibition, we focus this edition of our newsletter on profiling the extensive range of manufacturing facilities available within the Zeria Group. Being part of a global and fully integrated healthcare company is a key requirement for many of our customers as they increasingly rely on proven manufacturing expertise and a global reach.

Our technology article profiles our newly acquired ‘TA.TX Plus’ instrument for texture analysis which has been cited as an area of interest by several of our customers.

The last few years have witnessed considerable change and turbulence within the global pharmaceutical industry as many large companies have sought to divest their manufacturing assets and non-core development activities and rely more on external Contract Manufacturing Organisations (CMOs). This has been primarily driven by a need to reduce costs as drug patents continue to expire and fewer blockbusters are emerging from pharmaceutical pipelines.

Tillotts Services has reacted to these changes through providing an increasing range of contract development and CMO services together with a responsive and customer-centric approach. Our contract research capabilities are aligned to help our customers’ “fast-track” their development candidates and expedite

registration and product approval. We regularly work with smaller biotechnology companies who typically operate a virtually integrated structure and come to rely on our ability to meet their needs and essentially become an extension of their R&D department. We achieve this by facilitating close interaction at the scientific and project management level and adopting a flexible approach as project needs and goals often change.

Our manufacturing customers tell us that they want to be reassured that they are working with an established, secure and global manufacturing expert who can anticipate their future needs. We are able to address challenges at all stages of the pharmaceutical life-cycle; so we can help customers identify new formulations for a clinical trial or help develop a market extension strategy through an improved dosage form.

Issue 3

Responding to new industry needs in times of change

NEWSLETTER

Acknowledgements: Design by David Anthony, AK Design (Scotland) Ltd.

For more information, please contact us at:

Q: So André please tell us a little about yourself?

A: I have lived in Basel since 1992, where I moved to directly after finishing my apprenticeship as a galenical technician. Within my previous roles, I have been employed as an Associate Scientist at Novartis (2005-2009) and as a Senior Formulation Scientist at Geistlich Pharma AG (2009-2011).

My hobbies are computers, travelling, hiking, reading and music.

Q: When did you join Tillotts?

A: I joined in June 2011 and have been busy working on new customer projects and applying our technologies which I have enjoyed.

Q: What is your function at Tillotts?

A: As a Formulation Scientist I am involved in developing new formulations at the lab scale that will be transferred to production. Our key objective is to fully understand the potential scale-up challenges and ensure that we have a robust process. I enjoy the challenge of finding solutions to problem drug development candidates and working within a dynamic team.

Q: What was the biggest challenge for you at Tillotts?

A: Managing several demanding projects which typically have tight deadlines.

Q: Which project are you most proud of?

A: Transferring a laboratory process to production scale is always exciting for a scientist since it provides a definitive test of how well you have done your job and anticipated potential issues. It is a proud moment when the hard work of our team comes together and our customers’ have their product on time and on budget.

Q: What will be your next bigger challenge at Tillotts?

A: Our in-house research that is focused on a new approach to poorly soluble APIs is currently presenting plenty of challenges, however we have made good progress and now plan to file a patent. Once established, it will deliver a lot of confidence for Tillotts Services and for our potential new customers.

In the previous issue of our Newsletter we interviewed Thomas Kaiser, who heads up our engineering group. In this issue Claudio Scialdone interviews a relatively new employee André Solioz who works within our formulation development team and is based at our Ziefen site.

ww

w.tillotts.com T: +41 61 935 28 28

F: +41 61 935 28 29E: services@tillotts.com

Tillotts Pharma AGTillotts ServicesHauptstrasse 274417 ZiefenSwitzerland

Tillotts Services will be represented at the following events during 2011 and 2012. We would be delighted to meet with you.

Let’s Have Coffee..

Going to CPhI this month? Registration is free

(http://www.cphi.com/visitors) and Frankfurt is an excellent venue for what is a mammoth show with previous visitors from over 125 countries.Tillotts Services will be located at Exhibition Stand 41F67 in Hall 4.1

so please come and visit us.