pharmatec gmbh units for the production, storage and

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Pharmatec GmbHUnits for the Production, Storage and Distribution of High-purity Media

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Pharmatec GmbHA Bosch Packaging Technology Company

Manfred-von-Ardenne-Ring 5 01099 Dresden GermanyTel. +49 351 2 82 78-0Fax +49 351 2 82 78-20www.pharmatec.de

Printed in Germany100 % chlorine free paper

High-purity Media Systems | �

Contact Pharmatec for the planning, development

and production of: Ñ High-purity steam generatorsÑ Distillation unitsÑ HPW generationÑ Storage and distribution systems

for high-purity water and high-purity steam

Pharmaceutical products have a constant need for high-

purity media such as purified water, water for injection

and high-purity steam. Quality fluctuations or supply

bottlenecks for these sensitive pharmaceutical raw

materials are inacceptable for producers. In other

words, high-purity systems are central supply systems

which, if they fail or if the quality drops, can lead to far-

reaching consequences in the production units.

OverviewÑ Planning support to help decisions about the most

efficient solution (feasibility study on request)Ñ Basic and detailed engineering services going

as far as qualification (including full-loop calibration)Ñ Complete FAT in realistic operating conditions

(on request: including endotoxin challenge test)Ñ Customized sizes and functionsÑ Connections to process control systems (PCS)Ñ Individualized software applicationsÑ User ID password protection to 21 CFR Part 11Ñ Systems integration, e.g. feed water header

and WFI tankÑ Support with on-site installationÑ Remote maintenance using modem

High-purity steam generators from Pharmatec

Pharmatec is your partner for the development,

construction and manufacturing of individual high-

purity steam generators. To meet fast deadlines or

budget limitations, Pharmatec can provide standard

solutions with no reduction in quality.

Type pressure (bar) 4 bar (ü) 6 bar (ü) 8 bar (ü)

PSG 50 E 2 50 50 50

PSG 100 E 2 100 100 100

PSG 200 E 2 200 200 200

PSG 200 2 45 80 105

3 50 80

PSG 250 2 95 160 215

3 110 165

PSG 300 2 190 325 410

3 220 330

PSG 400 2 375 650 730

3 440 660

PSG 500 2 480 850 1120

3 165 600 890

4 355 685

PSG 600 2 690 1220 1600

3 240 860 1280

4 510 980

PSG 650 2 1130 2000 2900

3 395 1405 2085

4 840 1600

PSG 700 2 1650 2650 3800

3 505 2000 3250

4 1120 2210

PSG 800 2 2105 3770 4940

3 735 2630 3930

4 1560 3000

PSG 1000 2 2630 4730

3 915 3290 4950

4 1935 3790

High purity media units from Pharmatec

High-purity steam generators from Pharmatec can be used to produce from small to very large quantities of sterile, high-purity pyrogen-free steam. This high-purity steam is suited for: Ñ Sterilizing fittings (tanks, prepa-

ration vessels, piping systems, filling machines, filters, etc.)

Ñ Humidification of air in clean rooms with WFI quality steam

Optional: Membrane gas removal A compact vacuum gas removal unit basically consists of a membrane pipe module and a vacuum pump. It works on the basis of gas permeation through a semi-permeable membrane, by applying a vacuum to a filtration module through which the feed water flows. The unit is construc-ted so that there is no drop in high-purity steam produc-tion when the feed water degasifier is switched on or operated.

High-purity steam quantity (kg/h) for pressurized heating steam High-purity steam

Example of a PSG 500 high-purity steam generator

Optional: Thermal gas removal Thermal non-condensable gas removal can be used in special cases and with ozone sanitized systems. It is based on extracting the finely atomized feed water vapor in a degasifying tank. In this process, the feed water is conducted via a heat exchanger, where it is heated to a gas removal temperature, then nebulised using a spray nozzle into a tank which is surrounded by a vacuum.

Performance features

If a customer has a special request or requirements for the

removal of inert gases within the high-purity steam, in

accordance with EN285 and HTM2010, with proportions

< 3.5 by volume, Pharmatec can deliver degassing systems to

pre- treat the feedwater. We have membrane or thermal

degassing for this application.


Pharmatec high-purity media generators are constructed

following the principle of the natural circulation evapo-

rator. Here, special shell-and-tube heat exchangers are

used. The distillation process is based on an energy-

saving multi-stage principle. Driven by the density

gradient, the power of the natural circulation process is

used to create a circulating flow without any additional

energy. Our engineers and energy experts are constantly

improving the energy-efficient methods for the benefit of

our customers.

Multi-stage pressure column distillation units from Pharmatec

High-performance units for the genera-tion of high-purity media from Pharmatec

Type 4 bar (ü) 6 bar (ü) 8 bar (ü)

50-S1E* 50 50 50

100-S1E* 100 100 100

50-S1 45 80 100

120-S3 160 220 265

200-S3 250 350 410

250-S4 320 450 540

400-S4 420 680 840

500-S4 660 900 1100

700-S4 790 1270 1450

700-S5 790 1270 1450

1000-S5 1060 1700 2050

1000-S6 1060 1700 2050

1500-S5 1530 2450 3100

1500-S6 1530 2450 3100

2000-S5 1950 3150 4100

2000-S6 1950 3150 4100

3000-S6 3100 5060 6100

3500-S6 3600 5060 6100

4000-S6 3950 6150 8100

6000-S7 4900 8500 12100

Multi-stage pressure column distilla-tion units from Pharmatec These units consist of three to eight columns. The first is heated with steam (optionally: electricity). The proceeding columns are heated using the high-purity steam produced by the previous columns. The conti-nuous monitoring of the distillate by the control system means that distillate of insufficient quality is rejected. This includes too high conductivity or a non-permissible temperature.

Pharmatec multi-stage distillation units are designed for

the production of sterile, non-pyrogenic water for injec-

tion (WFI). Only the first column of the distillation unit

needs to be heated with plant steam. In the case of

units with seven to eight columns with the use of

pre-heaters, the WFI product cooler is not required,

as an external cooling medium is not needed.

Optional: Triple mode still As well as the generation of WFI, there is often a need in pharmaceutical processing units for fairly small quanti-ties of high-purity steam, e.g. to sterilize sampling devices, lab equipment or short pipe sections. The first column can optionally be used as an indepen-dent high-purity steam generator. Small quantities of high-purity steam can also be removed at the same time, i. e. simultaneously, during the distillation process.

Example of a multi-stage pressure column distillation unit, type 1000-S6

Distillate production (l/h) with pressurized heating steam

Performance features (*electric heating)

Pharmatec multi-stage distillation units’ unique pro-

cess for eliminating pyrogens is based on the com-

plete separation of the feed water and generated

steam, with low steam rates. A specially developed

baffle/reversing system is designed to almost entirely

remove water drops from the steam produced in

accordance with pharmaceutical laws.

Conceptual diagram of „Blow down“

Concept sketch of Pharmatec Natural circulation evaporator Concept sketch of „Triple mode still“

feed water

pure steam

heating steam

condensate

coolingwater

WFI

waste

„ON“ for WFI generation

„ON“ for RD generation

„ON“ for combinedWFI/RD generation


Successful projects start with project management Ñ Efficient, transparent project management: we

constantly inform you about the project’s progressÑ Pharmatec is certified in accordance with

DIN EN ISO 9001:2000Ñ Shorter delivery times for fast-track projects

available on request

Successful projects need qualified staff Ñ Process engineers and software engineers with many

years’ processing expertise in planning, construction

and automationÑ Practice-oriented mechanics, orbit welders and flexible

fitters in production and final assemblyÑ Experienced service technicians can take on various

tasks on our customers’ sites Ñ Specialists and experienced qualified staff fulfill our

customers’ individual requirements and wishes

Successful projects can be provenÑ Manufacturing traceabilityÑ Documentation – in all main languages –

from the first R & I draft until handoverÑ cGAMP documentation

Successful projects end with a high-quality product

which meets your demands Ñ Compact construction with minimum floor space requiredÑ Parts which come into contact with products come com-

pletely in premium steel 1.4404/1.4435 (AISi 316L) Ñ Frame profile, insulating sheath and switch cabinet in

premium steel (AISi 304)Ñ Control components from Siemens, Allen-Bradley,

Schneider TelemecaniqueÑ Manufactured in accordance with the European Pressure

Equipment Directive 97/23/EC, ASME, SVTI, CODAPÑ Exceeds all requirements in the United States

Pharmacopeia (USP), European PharmacopeiaÑ Effective separation of pyrogens at low steam speedsÑ Suited for low or changing pressure of heating steam or

feed waterÑ Improved setup for high efficiency

On request: Ñ Ra < 0,5 µm surface qualities and electropolishingÑ Delta-ferrite content of 0.5 % to 1 % Ñ Specially manufactured fittings and meters

In pharmaceutical production, high-purity media systems

are used to supply the most important processes. High-

purity media such as WFI and PW are generated, stored,

distributed and used. So that enough medium of suffi-

cient quality is available for every recipient at all times,

the storage and distribution system is customized to

precisely suit the requirements of the production or lab

area.

Requirements for the material, the selection of the

components themselves and the fulfillment of legal

regulations for pharmaceutical construction play a deci-

sive role in fulfilling the high quality requirements for

WFI and PW storage systems.

Ñ GMP- and FDA-compliant setup and adaptation of

production efficiency to fit with storage capacity and

quantities purchasedÑ Validation and guaranteeing of parameters critical

to the process (flow rate, throughput, pressure,

temperature, conductivity)Ñ FAT at Pharmatec – on test benches with equipment

to provide realistic proof that the unit fulfils all user

requirement specifications (URS)Ñ Route planningÑ Tap connection managementÑ Assembly management

Storage and distribution systems for WFI, PW and high-purity steam from Pharmatec

Customized quality units from Pharmatec

Pharmatec develops, constructs and manufactures: Ñ WFI storage and distribution

systemsÑ PW storage and distribution

systemsÑ Distribution systems for high-purity steam

P + I-Diagram

Pharmatec GmbHProcessing and Biotechnology systems

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berm

olde

nhau

er.de

0005/01

Pharmatec GmbHA Bosch Packaging Technology Company

Manfred-von-Ardenne-Ring 5 01099 Dresden GermanyTel. +49 351 2 82 78-0Fax +49 351 2 82 78-20www.pharmatec.de

Printed in Germany100 % chlorine free paper

� | Lorem ipsum dolor sit Processing and Biotechnology systems | 3

Upstream and downstream biotechnology units from Pharmatec

Processing and bio-technology systems from Pharmatec

Preparation systems, units for fermentation and purification In the field of biotechnology and processing units, Pharmatec develops, constructs and produces the following: Ñ Preparation units for hygienic,

aseptic and sterile processes, with isolation technology

Ñ Systems for inactivation and neutralization

Ñ Systems for sterile filtrationÑ Integration/complementing of

upstream and downstream processesÑ Fermentation systems

(in cooperation with partners) Ñ Sterilization units for substrate

solutionsÑ Provision of buffers for chromato-

graphy units with fraction collectorsÑ Systems to provide buffers and

prepare substratesÑ Harvest linesÑ Filtration systems (nanofiltration,

crossflow and ultrafiltration)

Isolating and purifying substances extracted by means of

bioprocessing is a multi-level process which sets high

demands in terms of unit technology and process control.

As a unit manufacturer, Pharmatec is a global service

provider acting as a partner to the pharmaceutical

industry. Fermentation media are complex mixtures of

different substances where the final product is intra-

cellular or in a diluted solution. At 40 % – 90 %, the recon-

ditioning costs make up a considerable amount of manuf-

acturing costs. The steps of separating out the solid

phase, cell disruption, concentration, purification and

formulation all come under the heading of downstream

processes. The solids can be separated using means such

as filtration, centrifugation and sedimentation. Cell dis-

ruption can be caused by mechanical methods, by osmo-

tic pressure or using enzymes. Pharmatec delivers units

for the preparation of buffer media and integrates units

for filtration and add-on chromatography units. For the

buffer preparation, the solid or liquid buffer substances

are placed in the containers and dissolved in purified

water or WFI (water for injection). Using ultrafiltration

modules integrated in the unit, the final product is con-

centrated before further reconditioning steps and after

chromatography steps. During filtration, other compo-

nents can be measured in depending on the conductivity

and permeate flow. A chromatography unit integrated into

the unit is available to further purify the product. The

buffer is supplied and the fractions collected using the

containers in the processing unit.

Example of a downstream processing unit (1 x 200 l, 4 x 600 l, 1 x 1,200 l)

Contact Pharmatec for the planning, development and

production of:Ñ Upstream and downstream biotechnology units Ñ Preparation systems Ñ CIP/SIP units Ñ Wastewater deactivation units

The growing amount of active substances which are

produced using biotechnology is changing the structure

of pharmaceutical production units. Highly complex

biochemical reaction mechanisms demand higher and

higher levels of purity and thus more efficient purifica-

tion steps in the units. Pharmatec’s processing and

biotechnology systems are characterized by many years

of experience in development and construction, as well

as of uncompromising production quality.

Overview of processing systemsÑ Preparation units for hygienic, aseptic and sterile

processes, with isolation technologyÑ Storage systems with transfer pipesÑ Systems for inactivation and neutralizationÑ Systems for sterile filtrationÑ Transfer and handling systems

Overview of biosystems Ñ Integration/complementing of upstream and

downstream processesÑ Fermentation systemsÑ Sterilization units for substrate solutionsÑ Provision of buffers for chromatography units

with fraction collectorsÑ Harvest linesÑ Filtration systems (nanofiltration, crossflow,

ultrafiltration)


Bioprocess expertise from Pharmatec

Ñ Controlling the unit using PLC – at the client’s requestÑ Operation with an operating panel or PC

(various visualization systems possible) Ñ Complies with 21 CFR 11Ñ Can be connected to a higher-level process

controlling system Ñ Control in accordance with GAMP Ñ Construction avoids dead legs Ñ Pipes and fittings laid out to enable complete

evacuation Ñ Built entirely in 1.4404 or 1.4435 premium steel

Pharma Biotech procedures

Media Protection and Substrate Preparation

Sterilization

Fermentation

Product Packaging

Sterilization

upst

ream

dow

nst

ream

Residual disposal

ExpertisePharmatec

Product

Ñ Surface roughness < 0.8 µm Ñ Welding mainly carried out using orbital welding

technique Ñ Unit documentation in accordance with FDAÑ Optional: design in 1.4539 premium steel Ñ Optional: Smoother surface thanks to special

treatment such as electropolishing Ñ Optional: Additional tests such as video endoscopy,

X-ray test Ñ Optional: Compliance with delta-ferrite content

pursuant to BN2

Example of a bioprocessing unit (2 x 1,000 l)

Harvesting

Product Purification

Integration of filtration systems (UF/NF)

Integration of separators

Integration of chromatographs

Integration of buffer/ processing vessels

CIP

CIP

ExpertiseBoschbusiness union

Upstream and downstream biotechnology units from Pharmatec


Preparation systems from Pharmatec

Preparation system expertise from Pharmatec

Some of the main components of a preparation system are: Ñ Pressure-resistant processing

containers in accordance with guidelines on pressurized devices, with or without double wall

Ñ Magnetic mixers with frequency regulator

Ñ Sterile ventilation and product filters with certified integrity

Ñ Pumps: circulation, metering, vacuum or transfer pumps

Ñ ValvesÑ Calibrated metersÑ Automation system and process

controlÑ Integration of preparation isolators

Example of a preparation system (preparation vessels 3 x 500 l, 1 x 50 l; buffer vessel 1 x 125 l; CIP vessel 150 l)

Preparation systems with RAPS

(Restricted Access Barrier Systems)

Pharmaceutical processing units are becoming more and

more complex, and set extremely high demands for

operator safety, protection against contamination and

product protection, not only in the field of bioproces-

sing. Despite the degree of automation in the field of

preparation, manual interventions are absolutely neces-

sary to implement formulations. Processing units to

produce cytostatics or other products which inhibit

cellular growth often require manipulation when adding

active substances and solid or liquid substances in

extremely small pre-weighed quantities. In this case,

precise doses can only be added manually. The ideal

solution for a method which is very safe, protects the

operating staff and protects the product from contami-

nation is “Restricted Access Barrier Systems”, or RAPS

for short, or isolators. Both companies have a long

tradition of the combination and connection of Pharma-

tec processing units with Bosch isolator systems, proce-

dural calculation, and expertise in cleaning and sterili-

zing complex isolator/unit systems.

Example of a preparation isolator

Pharmaceuticals are substances or preparations which are

designed for use on or in the bodies of humans or animals.

The fundamental rules for their quality and the substances

and processes used in manufacturing them are clearly

defined and described in international laws. These sets of

rules are used as a principle in planning and project plan-

ning for sterile preparation systems. The high standards

set down for cleanliness and sterility when manufacturing

pharmaceuticals reveal the obvious value placed upon

processing units of this type in the pharmaceutical

industry. Pharmatec has made this high status the focus of

its core business and can provide complete production

units for manufacturing parenteral or oral products all over

the world. Due to the variety of different processing steps

and technological procedures, concepts for preparation

lines vary; Pharmatec engineers adjust them to fit custo-

mers’ requirements perfectly. Procedural processes for

the manufacturing of the above products often start

with the introduction of raw and auxiliary materials, with

liquids or solids being measured out extremely precisely

using weighing systems or flow rate metering. Mixing

processes with high-performance mixers which are

gentle on the product; temperature control procedures

with extremely close tolerances and very high precision,

and sterilization programs, secure the long-term future

of the company’s processing expertise in pharmaceuti-

cal unit construction. To maintain values such as the pH

value, conductivity, concentration and density, which are

critical to the process, process engineers and auto-

mation engineers create special program flows which

are turned into GAMP-compliant automation systems to

fulfill the customer’s wishes.

Processing and Biotechnology systems | 9

CIP/SIP units from Pharmatec

Mobile CIP systems from Pharmatec

CIP/SIP biotechnology units from Pharmatec are individually adjusted to customers’ requirements. Pharmatec develops, constructs and manufactures CIP/SIP units for: Ñ cleaning buffer preparation

systems, fermenters, filling machines

Ñ single vessel (mobile or fixed)Ñ or complex multi-vessel unitsÑ closed-loop or single-use cleaning

systemsÑ complete integration into the

processing units to be cleaned

Pharmatec’s services: Advice and

planning, all the way down to putting

together one or more CIP unit sys-

tems, including the supply and return

lines to the processing units and

piping to be cleaned. To automate

the process, validated software

modules are used to create a greater

degree of standardization. The start-

up and qualifying costs are reduced

thanks to effective project planning.

At the same time, the high reliability

of the tried and tested fast-track

module increase the units’ availabi-

lity, allow them to be inspected

safely, make troubleshooting easier

and thus contribute to the safety and

reproducibility of the procedures.

Pharmatec’s mobile cleaning centre is designed as a

CIP unit and automatically carries out procedural steps

in the cleaning of important components which come

into contact with products in processing units and

filling and packaging machines. The unit is designed as

a mobile unit which is ready for immediate operation.

Components: Ñ Tank, 500l, for cleaning solution/rinsing waterÑ CIP supply pump with built-in frequency converterÑ CIP return pump with built-in frequency converter Ñ Measuring pumps for adding alkaline and

acidic cleaning agentsÑ Electric/steam heated exchangerÑ Chassis (approx. 2,500 x 1,200 x 2,000 mm

[L x W x H]) Ñ Pipes, valvesÑ Pressure reduction and sterile filter for

compressed airÑ Metering and regulating devices Ñ Control cabinet with power section and unit control Ñ Electrical and pneumatic installationÑ Control system with operating systemÑ External interface

Conceptual diagram of CIP unit Ñ Compact, modular unit structureÑ Tried and tested standard compo-

nents used from selected suppliers Ñ Design with little or no dead space

makes it easy to clean yourself Ñ Optional: SIP design (for inline

sterilization)

Example of a four-vessel CIP unit (4,000 l RW-model; 3 x 2,000 l pre-rinsing water, acid, leach)

CIP – Cleaning in PlaceSIP – Sterilization in PlaceDIP – Drying in Place

CIP return

Shell-and-tube heat exchanger

CIP supply

Metering pump

Detergents

CIP tank

Item to be cleaned

Mobile CIP unit

Processing and Biotechnology systems | 11

Wastewater inactivation units from Pharmatec

Inactivation units from Pharmatec

Biotech procedures to produce active substances are

widespread in the pharmaceutical industry. One important

link in the production chain is disposing of production

waste. The law sets down regulations on this point to

minimize risks to people and to the environment. For

inactivation, a wide temperature range is available, from

80 – 135°C, which can be selected depending on the type

and concentration of the bacteria to be inactivated.

Thanks to the construction of the unit and the controls,

which are adjusted to it, the wastewater is kept in the unit

in liquid form above boiling (at normal pressure).

Pharmatec develops, constructs and produces inactivation units which can run continuously.Ñ Thermal inactivation of wastewater

contaminated with biological materials Ñ Treated wastewater fulfils all legal

requirements (safety level BSL 1, BSL 2, BSL 3)

Ñ Lower energy use than with units which do not run continuously

Example of an inactivation unit which runs continuously (2,500 –4,000 l/h)

Thanks to the adjustable volume flow at which the

wastewater is conducted through the unit, the inactiva-

tion level can be adjusted to the quantity of wastewater

occurring at any time. This minimizes energy-sapping

starting-up and switching-off procedures. The heat

maintenance section is designed as a coil and also acts

as the base of the unit. Above it come three heat

exchangers (heater, recuperator, cooler). To detect any

leaks, the base stands in a basin equipped with liquid

sensors.

Biosafety level (BSL) classification

When dealing with biological agents such as viruses,

bacteria and fungi, corresponding safety regulations

must be complied with in accordance with the law on

genetic engineering. Depending on the biosafety level,

the danger of infection due to contact with the biologi-

cal agents must be avoided by using appropriate sealant

systems (e. g. double mechanical seals with isolating

pressure vessels), (de-)aeration, sampling systems and

sterile barriers.

BSL 1Ñ Risk level: Very little or no risk to individuals or the

population. Ñ Potential risk: Humans or animals are not expected

to fall ill.

BSL 2Ñ Risk level: Moderate risk to individuals, low risk to

the population. Ñ Potential risk: Humans or animals may fall ill, but

there is no serious danger to lab personnel, the

population, livestock or the environment. Contacts in

the lab can lead to successful infection but effective

treatment and prevention measures exist. There is

limited risk of spreading.

BSL 3Ñ Risk level: High risk to individuals, low risk to the

population.Ñ Potential risk: Humans or animals are expected to

become seriously ill, but it is not usual for the infec-

tion to spread from one infected host to the next.

There are effective treatment and prevention

measures.

BSL 4Ñ Risk level: High risk to individuals and the

population. Ñ Potential risk: Humans or animals are expected to

become seriously ill, but it is not usual for the infec-

tion to spread from one infected host to the next.

There are effective treatment and prevention

measures.

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