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www.hecht.eu

Risk Management

and Trends for

highly potent

products

INTERPHEX 2011

in New York, USA

23.02.2011

2Risk Management and Trends for highly potent products

Agenda

Global outsourcing a risk to the

manufactured product?

About Containment

Trends for highly potent products

Risk assessment


Speaker

Richard Denk is Director of Sales and

Marketing of HECHT Technologie GmbH.

He organizes workshops on containment,

qualification, validation and hygiene both in

Germany and internationally and has already

published various technical papers on this

subject as well as written a paperback

concerning Containment & Hygienic Design.

In addition, Richard Denk is the head of the

ISPE Containment Group and has

contributed to the new ISPE OSD Baseline

Guide.

Richard Denk

HECHT Technologie GmbH



manufactured product?

Where in the world are your products

or parts of your product produced?



manufactured product?Products throughout the world


About Containment

How protected is the product or the environment during all the

manufacturing steps?


About Containment

Different GMP Requirements „ EU, USA, China, India…..“

Different EH&S Requirements


Product protection

Protection of the product

against cross-contamination

and impurities

Operator/Environ-

ment protection

Protection of the operator

against hazardous materials

(toxic, mutagenic, carcinogenic)

Protection of the Environment

GMP vers EH&S

About Containment


More high active or

hazardous products

manufactured globaly.

About Containment


Production of hormones Production of mutagenic

or genetically modifying

products

Production of

carcirogenic

products

What additional risk does highly active or highly hazardous

substances have to the current trend of Globalisation?

About Containment


About Containment

Containment pyramid


About Containment

Explanation on Containment

Question:

“How many spoons

are maximally allowed?“

Clean room Detached house Leaning Tower

of Pisa

Big Ben Tower Notre Dame de

Paris

Cologne

Cathedral

Empire State

Building


Different understanding

about clean.

About Containment


How many impurities are in your product before you receive it and

before GMP is applied?

Traceability of your product during all the production steps as well

as information about other produced produced in the same facility.

About Containment


How many impurities are allowed to be safe. ADE Acceptable

Daily Exposure.

About Containment


Trends for Highly Potent Products


Are current process technologies suitable for high potent

production?




Pharmaceutical Formulation

API

Pharmaceutical



Current Process Technologies are designed to manufacture

pharmaceutical products.

The use for multi purpose application is possible but for highly

active or highly hazardous products critical.

Large surfaces and a lack of hygienic design makes the

cleaning not easy. E.g. ADE



The product contact part is often equiped with additional

features like Filter, Agitators… .

Re-pollishing of product contact part surfaces to revalidate the

cleaning.

Mantenance. Critical for highly active or highly hazardous

substances.



High Shear Mixer Large Filter

Large Surfaces

Large Sealings

Additional Equipment like chopper

and agitator



Fluid Bed Dryer

Large Filter

Large Surfaces

Large Sealings



Y Blender

Large Filter

Large Surfaces

Large Sealings

Not easy to empty and fill


Tablet Presses


Very complex technology

Not easy to clean

http://upload.wikimedia.org/wikipedia/commons/5/5a/Tablet_press_animation.gif



Does other areas already use better technologies like BioTech?


Are current process technologies suitable for high potent

production?



Make Skan Switzerland

Make ART Germany

Make BDK Germany

Make Extract Technology UK

Make PSL UK

Make HECHT


Stainless Steel Isolator Technology



Split Cone Systems SCS

Split Cone System

Make Matcon UK

Make Ucon Germany

Split Cone System

Make HECHT Visval Germany

D:/Denk/Vorträge/Videos deu/ContainerMatcon.mpeg

D:/Denk/Vorträge/Videos deu/ContainerMatcon entleeren.mpeg

D:/Denk/Vorträge/Videos deu/SoliBag_Entleerung.wmv

D:/Denk/Vorträge/Videos deu/Befllung_050705.wmv

../../Vorträge/APIKopenhagen/MOV01037.MPG



Make Buck Germany

Make Glatt Germany

Make Andocksysteme Germany

Make Mueller Germany

Make PSL UK


Split Butterfly Systems SBS


Make HECHT Germany

Make HECHT Visval Germany

Make ILC Dover USA


FIBC „Big Bag“ Technology

G:/Entleerung_050704.wmv

D:/Denk/Vorträge/Videos deu/SBK_SAS_deu768x432.mpg

D:/Denk/Vorträge/Videos deu/PCwechsel_deu_768x432.mpg

D:/Denk/Vorträge/Videos deu/LBK_LAS_deu768x432.mpg


Endless Liner Technology

Make HECHT Germany

Make ILC Dover USA




Flexible Liner Technology

Flexible Isolators Expendable weighing

isolator

Expendable sampling

system



Example:

Expendable dosing

and decanting

system with double

O-ring-port and

active-passive

weighing unit.



Rigid system

Rare product change

Low requirements on cleaning

Rigid processes

Limited process intervention

Time-consuming cleaning

High initial investment

Flexible system

Frequent product change

High requirements on cleaning

High flexibility in process control

Easy process intervention

No cleaning

Cost saving


Comparison of costs: flexible - rigid

Example: High Containment OSD Facility

Pos. 1:

Dispensing

Pos. 2:

High

Containment

DispensingPos. 3:

Formulation Pos. 4:

Lubricant

Blending

Pos. 5:

Compression Pos. 6:

Compression Pos. 7:

Coating Pos. 8:

TabletPos. 9:

Tablet

Pos. 10:

Packing




Pos. 1:

Dispensing

Pos. 2:

High Containment

Dispensing

Pos. 3:

Formulation

Pos. 4:

Lubricant

Blending




Pos. 5+6:

Compression

Pos. 7:

Coating

Pos. 8+9:

Tablet

Pos. 10:

Packing




0 €

1.000.000 €

2.000.000 €

3.000.000 €

4.000.000 €

5.000.000 €

Rigid Bin Solution

FIBC Flexible Disposable Solution

5.000000 €

2.850.000 €

Investment costs:

Rigid bin solution and flexible solution (FIBC Flexible Disposable Solution)




0 €

500.000 €

1.000.000 €

1.500.000 €

2.000.000 €

2.500.000 €

Rigid Bin Solution

FIBC Flexible Disposable Solution

588.000 €

365.000 €

2.352.000 €

1.460.000 €

3 months

3 months

per year

per year

Consumable costs:





Rigid Bin

Solution

FIBC Flexible

Disposable Solution

Investment costs 5.000.000 € 2.850.000 €

Consumable costs (per year) 2.352.000 € 1.460.000 €

Life cycle costs (10 years) 28.520.000 € 17.450.000 €

Total costs comparison:




Example:

API production

Big Bag Entleeren in den Reaktor Umwandlungsstation

Reaktor Reaktor

Zentrifuge

Big BagBefüllen + Entleeren

Trockner

Kleingebindebefüllung

Pos. 3:

Reactor

charging

Pos. 2:

Transfer system

Pos. 1:

Sampling

Pos. 4:

Centrifuge discharging

Pos. 5:

Dryer filling

Pos. 6:

Dryer

discharge and

filling in drums



Example: API production,

Rigid Containment


Risk assessment


Risk assessment

Containment is the most complex interaction of

technologies,

GMP,

buildings,

product,

operator and

environment

in the pharmaceutical and API industries.


Successful risk assessment

Regulatory Knowhow:

Baseline Guide, Containment

Steering Committee

Process Knowhow:

Wirkstoff - Pharma

Experts on Bulk Material Handling, Containment and System Solution

Provider

Experts on HygienicDesign:

3A „USA“ EHEDG „EUROPE“

Turn Key Containment

Solutions


Risk between Design, Installation and final

operationStainless Steel Isolator Technology


Current situation

Comments


Current situation

Comments


Current situation

Comments


Current situation

Comments


Risk between Design, Installation and final

operationSplit Butterfly Systems SBS


Current situation

Example rigid system: Valve technology

Comments



Risk assessmentPersonal

Risk assessment tools according to

the ICH Q9: FMEA, HACCP,

HAZOP, etc.

Important: The best method does

not work properly without

knowledge of the writer about the

critical areas within an API and

pharmaceutical production.

Don‟t ask: “Who„s to be blamed?”

But rather: “Who hasn„t been

trained?”


Schirmbeckstraße 17

85276 Pfaffenhofen

Germany

T +49 8441 8956-0

F +49 8441 8956-56

[email protected]

www.hecht.eu

Thank you for your attention

mailto:[email protected]

mailto:[email protected]

http://www.hecht.eu/

Documents

Risk Management and Trends for highly potent products€¦ · High Shear Mixer Large Filter ... Trends for Highly Potent Products Split Cone Systems SCS ... Risk Management and Trends