packazine-01-07 pharma eng - syntegon japanfor convenient and easy-to-use products – it is also...

packazineIssue 01/2007

Adamed | Take a deep breath Hikma | Powder manufacturing under optimized aseptic conditionsBLS | Bosch Lab Systems – Throughput counts

packazine-01-07_Pharma_ENG.indd 16 04.04.2007 16:55:38 Uhr

2 | packazine Table of contents | Editorial

www.bosch.com/pa [email protected]

04 06 10

News

Facts & Trends

04 Increasing popularity of prefilled syringes

Customers & Markets

Pharma & Cosmetic

06 Adamed | Take a deep breath – Inhaler systems on the march

08 Service | Old becomes new

10 Hikma | Powder manufacturing under optimized aseptic conditions

13 Bosch Lab Systems | Throughput counts

Events

15 Pharma 2007

Cover

Your competent partner for

pharmaceutical solutions

Friedbert Klefenz

President Bosch

Packaging Technology

Table of contents


packazine | 3

13

Dear Readers,

After we had the opportunity to celebrate three centennials in the past year, the

20th of October 2006 gave us a renewed cause for celebration.

We officially opened our new location in Hangzhou (China) with

a magnificent celebration. Customers, suppliers, employees and

other guests fêted the completion of the premises and toasted to

a successful future. As has been shown, this was for a very good

reason: Emerging markets such as China and India have registered

strong growth. In these countries we achieved an extremely gratifying

growth rate of over 50 per cent in turnover. In addition, the incoming

orders of the entire group have also developed very positively in the

past financial year and at 17 per cent lie over the average market

growth rate (11 per cent). The World Packaging Organization‘s award of the “World

Stars” for the new “Pull Pack” flexible bag package gave us an additional reason to

celebrate. This award is only presented for packaging with the highest level of quality,

innovation and technology. In the recent past, combinatorial chemistry and high-

throughput research has significantly changed the way the pharmaceutical industry

develops new drugs.

Currently a similar paradigm change is happening in the chemical industry. Automat-

ed high-throughput synthesis and screening methods for the development of more ef-

ficient catalysts as well as better materials and formulations open new, efficient and

faster methods of materials research. Together with BASF, Bosch Lab Systems has

designed a robotics unit that for the first time permits a comprehensive investigation

of complex coating formulae. This innovative concept is scalable for the most diverse

applications.

The application areas for inhalers are being constantly extended. The filling lines,

cartoning machines and flexible bag makers from our product portfolio allow us to

profit from this welcomed market development.

Surely you noticed the new organization of the Packazine into Pharma and Food/Non

Food sections. I wish you even more reading enjoyment with this new reader-friendly

design!

Friedbert Klefenz

Friedbert Klefenz

President Bosch

Packaging Technology

Editorial


20062006200620062006200620062006 20072007200720072007200720072007 20082008200820082008200820082008

Worldwide Prefill Growth12,8 % CAGR

Quantityin Billions

years

2,500

2,000

1,500

1,000

500

20092009200920092009200920092009 20102010201020102010201020102010 200620062006200620062006200620062006 200720072007200720072007200720072007 200820082008200820082008200820082008

Sales inMillions

years00

50

100

150

200

250

300

350

400

450

2002002002002002002002002009 29 29 29 29 2010010010010010010010010010

15 % CAGRMarket Growth for Self-Injection Devices

4 | packazine News Facts & Trends

Increasing popularity of prefilled syringes

Advantages and driving factors

of prefilled syringes

Self-filling a syringe can be a cumber-

some process, which is not only slow

but can also result in incorrect dosages

and spillages. The availability of prefilled

syringes introduced both convenience

and accuracy to self-administered

drugs. The increased use of prefilled

syringes is not only following the general

consumer trend of a growing demand

for convenient and easy-to-use products

– it is also driven by the pharmaceutical

producers as a consequence of improved

safety and the reduction in drug overfill.

The key advantages and driving factors of

prefilled syringes are:

Ñ Time, cost and resource savings

Ñ Convenience

Ñ Easier home use and use in

emergency situations

Ñ Prefilled dosage reduces medication

errors

Ñ Increased assurance of sterility

Ñ Easy storage and disposal

Ñ Fewer material costs

Ñ Elimination of vial overfill

Ñ Reduced risk of needlestick injury

Ñ Eliminates cross-infection from

needle re-use

Ñ Differentiation of product

Ñ Demand for technologies that

improve production

Ñ New solutions in the pen / auto-injec-

tors markets due to new formulations

suitable for self-injection

Ñ Needle safety regulations

Current market and requirements

These advantages of prefilled syringes,

together with the emergence of bio-

technology drugs in the early 1990s,

led to an enormous, worldwide surge

in demand and this product class still

offers the highest future growth. The

The last two decades saw an increase in the administration of

parenteral drugs by prefilled syringes. The worldwide market for

prefilled syringes alone is estimated at 1,500 billion units and

worth US $ 1.5 bil. (see graph 1).

Market Growth for Prefillable Syringes Market Growth for Self-Injection Devices1 2


packazine | 5

predicted annual growth rate of 10 %

can be explained by the increase in

home-care, with very different end-user

needs in self-injection (see graph 2).

Besides geographic expansion and the

shift to unit-dose packaging, the market

for biological parenteral applications has

also increased demand. Over the entire

last five years, the US market has been

growing by 20 %*. The US pharmaceuti-

cal packaging market is set to grow at a

compound annual rate of 3.3 % between

2004 and 2011. 16.8 % of this revenue

is set to come from the fastest growing

prefilled syringes sector. Frost and Sul-

livan stated that the European market in

2005 was worth US $300 million and is

growing at 8–10 % per annum.

Continuous innovation for safer

injections

Needles and syringes can expose the

user to an injury risk and the World

Health Organization estimates that, an-

nually, there are three million accidental

needle-stick injuries worldwide. In

November 2000, the US implemented

the Needlestick Safety and Prevention

Law. This was followed in Germany by

legislation to prevent needlestick injuries

and, more recently, the UK issued guid-

ance in 2005. As a result, the market for

pen injectors continues to benefit from

significant growth, while the whole mar-

ket for self-injection systems is changing,

with the increased use of prefilled

syringes and auto-injection devices in

new therapeutic areas.The pen injector

is a cartridge-based device designed for

frequent, usually daily, manual injection

of mainly diabetes or other hormone

replacement therapies.

Auto-injectors automatically insert the

needle and perform the injection and are

usually designed for use with fillable or

prefilled syringes.

Small details are of high importance

Medical personnel increasingly prefer

“ready-to-use” syringes for delivering a

precise dosage of a medication safely

and efficiently. To supply this market,

presterilized syringes are delivered in

sealed plastic containers, or tubs, direct-

ly to the filling and packaging operation,

eliminating the need for cleaning and

heat sterilization. Increasing numbers

of suppliers of presterilized, ready-to-fill

syringes have given this segment a

stronger market share compared to bulk

syringes, which need to be processed

prior to filling. Bosch began serving the

syringe market over 20 years ago and is a

world leader in sterile filling of ampoules,

vials, cartridges and syringes. Bosch is

now the first company to offer all the

production steps, from filling to inspec-

tion to final packaging, which allows our

customers to deliver a safer, and easier

to use, product to end users.

For more information please contact:

Denise Beele

Phone +41 52 674 80 53

[email protected]

* “Pre-filled Syringes Report”, 2005ONdrugDELIVERY


Maciej Adamkiewicz, owner

and CEO of Adamed

6 | packazine Customers & Markets Pharma und Cosmetic

Take a deep breath Inhaler systems on the march

Whether for the treatment of asthma, chronic bronchitis or diabetes II,

the application areas for inhaler systems are constantly increasing.

The Freedonia Group predicts an annual average growth rate of 11 % to

the year 2010.

Basically, inhaler systems can be

characterized as nebulizers, dry powder

inhalers or metered dose inhalers. For

nebulizers, glass or blow-fill-seal am-

poules are used as the primary package.

On Bosch compact lines, glass ampoules

are cleaned, depyrogenized, filled and

closed, followed by marking, checking

and labelling. Today, environmentally

friendly, mono-material boxes are fre-

quently used for the follow-on secondary

packaging. Bosch has also developed line

solutions for blow-fill-seal ampoules, in

which the ampoules are cut out, individu-

alized and then packaged as flowpacks

and finally into folding cartons.

Metered dose inhalers are assembled

prior to packaging and, with relatively

complex geometry, can present a major

handling challenge. With dry powder

inhalers, there is the additional require-

ment of reliable protection for the

powder dosages. Here, blister-packaged,

hard gelatin capsules, as well as dental

cartridges, are used. These can be

packaged, either individually, or together

with blister trays, on Sigpack Systems’

horizontal bag makers, in hermetically

sealed aluminum laminate bags.

A dry powder inhaler packaging solution

for Novartis, in England, was introduced

in the 2/2006 issue of Packazine. In

this issue we take a look at Adamed of

Poland.

Adamed – a growing company

Founded in 1986, by a family in the

medical profession, Adamed conducts

its own research, as well as developing,

producing and marketing generic and

licensed pharmaceutical drugs. Adamed

is one of the largest pharmaceutical

companies in Poland, with 500 highly

qualified employees and an 88 million

USD turnover.

Besides two factories in its Polish

homeland, Adamed has a site in both

the USA and the Ukraine. The company’s

growth is continuing, with a plant in

Spain already being planned.

One of the core principles at Adamed

is the uncompromising adherence to


Inhaler and blister in

the packaging machine

– reliably guided for an

efficient and troublefree

production run.

packazine | 7

quality standards. All production is

carried out in accordance with the

requirements of the European Union and

GMP (Good Manufacturing Practice). In

addition, research and development into

new products is an integral part of the

company philosophy. In the last three

years alone, 20 new patents for active

substances and new formulations have

been registered.

Adamed is a partner in many national

health education programs. One of these

is the “Deep Breath” program, which

is concerned with “chronic obstructive

pulmonary disease” (COPD). This pro-

gram provides public education on the

symptoms, causes and consequences of

the disease, as well as offering informa-

tion on the diagnostic and treatment

possibilities.

Inhaler packaging at Adamed

For packaging dry powder inhalers

and blister strips into a folding carton,

Adamed uses a horizontal cartoning

machine from the Bosch CUT series. Cur-

rently, the inhalers are manually placed

on the blister stacks. However, equipped

with seven servo drives, the CUT can be

easily adapted to fit new requirements

and is already set up to accept the

retrofitting of an automatic infeed.


Frank Scholl

Phone +49 711 811 57581

[email protected]


1 Washing machine RRU

2 RABS with glove ports

3 Filling and stopperting station FLP


Old becomes New

With the updating of two lines, GlaxoSmithKline Biologicals relied on

Bosch Packaging‘s experience of many years. The main focus was to

upgrade and increase the capacity of the new lines.

In 2005, GlaxoSmithKline (GSK)

Biologicals acquired the research and

production facilities of a well-known

pharmaceutical company in the United

States. Among the production equip-

ment, there were two lines for cleaning,

filling and closing of vials which Bosch

Crailsheim (Germany) had delivered

to the United States in 1999. These

lines, however, had never been put into

operation. In order to process its own

products on these lines, GSK Biologicals

needed a competent partner able to

bringing the machines to a technological

state complying with current require-

ments. It was thus self-evident to count

on the experience, which Bosch Packag-

ing Technology in Crailsheim had gained

in many years.

Professional adaptation to new product

range

The upgrading of the first line started

March 2006. Since October 2006 it

has been at a GSK site in Europe. After

having been adapted to the European

voltage system, it was equipped with

new size parts for processing 3 milliliter

vials. The sterilizing tunnel HQL 3480 was upgraded by retrofitting a belt

speed display. Furthermore, a new

turntable infeed was mounted, and the

Distributing an average of 3 million

doses a day, GlaxoSmithKline

Biologicals is one of the world‘s

leading vaccine manufacturers,

employing approximately 6,200

people worldwide. Almost a quar-

ter of its staff work on developing

new safe and effective vaccines.

GlaxoSmithKline Biologicals


packazine | 9

time-pressure filling system of the filling

and closing machine FLP 4080 was

upgraded. The second line, designed

for its original site in the United States,

is now able to process 3, 10 and 15

milliliter vials for freeze-dried and liquid

products. In addition, a new sterilization

and depyrogenization tunnel HQL 5221S was integrated.

Higher output by upgrade

The RRU 3063 washing machines of

both lines were upgraded to RRU 3084 washing machines. The gripper turret of

the washing machine was extended from

three to four grippers per cycle. As a re-

sult, eight instead of six vials are cleaned

at once. The output was thus increased

from 300 to 400 vials. In addition, the

washing machines were equipped with a

siliconizing station.

Barrier system – restricted sterile room

After the upgrade, both filling lines are

surrounded by a RABS unit (Restricted

Access Barrier System) enabling a pro-

cess, which is mechanically isolated from

the surrounding room. Interventions

into the process are only possible via

integrated gloves.

Reach a common goal

The close cooperation between the

teams of the two companies was a deci-

sive factor for the successful implemen-

tation of the project. All activities were

coordinated by the project managers of

GSK Biologicals and Bosch.


Walter Albrecht

Phone +49 7951 402 215

[email protected]

Ñ Competent contacts

Ñ Disassembly of machine at its

present site

Ñ Handling of customs clearance

Ñ Customized upgrade of the line

by experts in Crailsheim

Ñ Qualification and function tests

Ñ Shipment and reassembly

Ñ Validation and commissioning

Ñ Production start-up at customer

Ñ Update of documentation

Ñ Training of operating staff

Advantages of an upgrade by Bosch

1 Washing machine RRU 30842 Siliconizing station3 Sterilizing tunnel HQL 34804 Filling and closing machine with TPFS5 Gross-tare weighing6 BAD discharge7 Time-pressure filling system (TPFS)8 RABS with glove ports

1

23

45

56

7

8


AFG - stoppering in

continuous motion

principle

Production floor with

three powder lines in

„U-configuration“


The Portuguese branch of the Jorda-

nian pharmacy company Hikma Phar-

maceuticals PLC choose Bosch for their

new powder filling line, not just for the

machine delivery, but also as a partner

with the same goal: an optimized and

fully functional overall system.

Hikma develops, produces and sells

generic products world wide as licensed

and patented pharmaceuticals. Because

of a production enlargement of a new

antibiotic, they are building a new, highly

modern production space for three new

production lines. The annual output of

the new production lines can go up to 60

million units when fully operational.

Transferring know-how for a perfect

overall system

“We have been giving Bosch access to

our test results, labs and raw materials

so that the production machinery can

be optimized for our needs. Bosch, on

its part, cooperated very closely with

our Engineers and Quality Department

to deliver not only machines, but a fully

functional integrated system”, explained


Hikma production facility

at Terrugem, Portugal

packazine | 11

Powder manufacturing under optimized aseptic conditions

The filling of sterile powders is a technical challenge,

not just because of the precision filling. For the

continuously sterile process area a special know how

is necessary.

Eng. Amjad Wahbeh, Engineering Direc-

tor for Hikma Portugal . This was the

recipe for success.

Of great importance to Hikma was a

simple, compact and practical solution

for the most sensitive area within the

sterile area: the filling area. Bosch was

able to meet this challenge, and convince

Hikma, with the new Bosch powder

filling machine. The slim machine design

offers the best conditions for lengthy fill-

ing campaigns with short down periods

and low maintenance efforts. Format

changes and cleaning of the machine can

be easily accomplished because of the

simple disassembly and aseptic reassem-

bling of the machine parts. In addition

to this, the AFG 3020 is constructed for

space saving wall mount installation,

exactly as Hikma desired.

Innovative closure

With the new Bosch solution, not only

can Hikma use conventional aluminum

caps but the innovative Monovial®

closure can additionally be used. This

new closure makes it easier for medical


1

Placing of the

Monovial® closures

2

AFG – module

for sterile air supply

1 2


staff to prepare the filled powder for

infusion applications. This new closure

incorporates an attached needle, thru

which the filled powder can be mixed

with an infusion liquid (such as infusion

bag). The Monovial® closure minimizes

any non-sterile contact during the mixing

of the infusion bag, making it a very

desirable system to use.

Strict internal guidelines for the good

of the patient

Sterility is strictly required in phar-

maceutical production. In addition to

government standards, internal company

guidelines are followed to insure the

proper quality of the pharmaceutical

product.

It was important to Hikma to have an

absolute safe LF (laminar flow) system.

An LF system that would remain running

even during cleaning for product change

(such as cleaning of the air return duct-

ing) and even during a loss of power,

because a shut down for even a few

seconds of the LF system would mean

that the whole sterile area would need to

be re-sterilized. Because of this, Bosch

developed a special air recirculation

system for Hikma with two separate

return channels to maintain sterility

during cleaning and maintenance of the

machine .

Mock-Up: A gaze says more then

thousand words

Before construction and assembly began,

Hikma was able to interact with the

system at Bosch Crailsheim. The “mock-

up”, a true to scale replica, has proved

itself as a very useful option in the layout

of many projects. Not only the filling and

closing machines, with their dust safe

panels and glove ports, but the sterile

room wall and it’s windows were rede-

signed for Hikma. The realistic simulation

helped to optimize the line early and to

clearly show process planning and insure

the success of the overall project.

“For us that was something complete

new”, said Amjad Wahbeh. “Bosch liter-

ally forced us to decide to use a mock-up,

and I have to admit that we saw the

advantage of it very quickly. Mistakes

in the planning, and even the better

solutions, we were literally able to touch.

From my point of view, the mock-up was

one of the best investments we made.”

The evolution of this project and the final

results have proved themselves; and for

the future, Hikma is very interested in

an intensive business relationship with

Bosch.


Dieter Bandtel

Phone +49 7951 402 362

[email protected]


Robot Handling of

BLS Syringes

packazine | 13

Throughput counts

For the first time, a fully integrated ro-

botics system allows the comprehensive

testing of complex coating formulae,

from raw material formulation right

through to the finished coating product.

BASF is ranked among the leading

chemical companies in the world. In or-

der to maintain its worldwide leadership

in the chemical coatings sector, the BASF

business unit, “Performance Chemicals”,

uses the innovative High Throughput

Screening technique for formulation and

coating applications.

Wide range of coatings

During the optimization of coating

raw materials and the investigation

of structural relationships in coating

formulations, a great variety of different

solid and liquid feedstock must be mixed,

or dispersed, and, if necessary, also

standardized in terms of solid content,

viscosity or pH value. A wide range of

coating systems need to be tested and

this would not be possible without the

syringe dosing system developed by

Bosch Lab Systems (BLS).

Reproducible production of test panels

For the investigation of product proper-

ties, newly developed coatings must

be reproducible and industrial-quality

coatings applied to test panels or other

substrates. Alongside classical doctor

blade technology, the BLS-developed

spray procedure (winner of the “2005

Color and Coating Prize”) is also used.

The subsequent hardening of the coating

film takes place directly in the unit,

either thermally or by ultraviolet radia-

tion.

Fast and objective testing

For BASF and its customers, the quick

availability of detailed and meaningful

test results is important. For this reason,

many established testing methods, such

as the measurement of color, gloss or

Bosch Lab Systems

and BASF develop

ultramodern, high

throughput screening

systems for coating

development



layer thickness, have been integrated

into the system. New automation tech-

niques, for the determination of scratch

or chemical resistance, were jointly

developed by Bosch and BASF.

High capacity

The modular design of the system and

the simultaneous processing of several

production steps allow up to a 100 dif-

ferent coating systems to be processed

within a short period of time. For the

first time, one system integrates innova-

tive dosing, application and measuring

techniques, as well as process control,

and permits the targeted production,

application and hardening of coatings, as

well as the fully automatic determination

of the coating characteristics. Due to

the modular design and the robustness

of the modules, this flexible system can

also be used in other application areas,

such as the development of adhesive

materials, detergents, cosmetics or

pharmaceuticals. The new system is cur-

rently being installed in Ludwigshafen,

Germany, by BASF, together with Bosch

employees, and will be available during

the year to BASF‘s internal and external

customers.

Bosch Lab Systems develops and very

successfully markets high throughput

technologies and laboratory automation

for the efficient and fast development of

new materials and formulations. An em-

phasis is placed on the implementation

of customized development processes

that provide industrial-quality, highly flex-

ible and modular automation solutions.


Dr. Thomas Brinz

Phone +49 711 811 58001

[email protected]

Dr. Roland Emmerich

Phone +49 711 811 58008

[email protected]

High Througput-System for Formulations Typical BLS-Syringes


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