GMP WASHING FOR BIO-PHARMA PRODUCTION · 2016. 12. 6. · GMP Washers are specially designed to...

GMP WASHING FOR BIO-PHARMA PRODUCTION

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AGENDA

• Intro to GETINGE

• Why GMP Washing? Where GMP Washing?

• Not all washers are GMP capable.

• GMP and LAB washers.

• Specific characteristics of GMP washing

• Hardware

• Documentation

• Racks ( Personal favourite!)

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Getinge Group in brief

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Getinge Life Science

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5

Product portfolio

Getinge Life Science

GMP WASHING

WHY AND WHERE?

• Original emphasis was to prevent cross contamination

between:

Non-penicillin drug products and penicillin drug

products

Drugs with potent steroids or hormones

• 1963 GMP regulations (part 133.4) required that

“equipment shall be maintained in a clean and orderly

manner”

• 1978 (211.67) updated the previous version and is still

the basis of design today

• CFR: Code of Federal Regulation, acts as the force of

law behind GMP

Why is cGMP cleaning required?


Reasons why GMP cleaning in pharmaceutical facilities is important:

1. To prevent contamination of drug product during manufacturing.

2. To prevent cross-contamination between different batches.

3. To prevent cross-contamination between different products within

same facility.

4. To ensure quality, effectiveness and safety of drug product.

5. To protect patient’s health:

• « Poor CGMP conditions at a manufacturing facility can ultimately pose a life-

threatening risk to a patient. »

• Guidance Industry – Current Good Manufacturing Practice (September 2004)

• Local/National Drug Authority (eg. US FDA) is

entitled to close/suspend manufacturing process

within a facility.

• Random inspections of all aspects of the production

cycle.

• Cleaning process is part of the production cycle!

• Most common inspection issues:

Lack of process validation

Lack of cleaning validation (SOPs)- Specially

manual cleaning.

Lack of QC lab controls

• “Acceptable level” criteria

• ANVISA?


Fields of applications

BIO-PHARMACEUTICAL PRODUCTION has

many areas and support facilities for each

pharmaceutical type and its manufacturing

process:

• Injectables: vials, ampoules, syringes

• Other liquid forms: syrups, liquid drops

• Semi-solid forms: suppositories, gels,

creams

• Solid forms: tablets, capsules, effervescent

tablets

Biologicals is specialy important!

In Research and Development

Departments:

• Formulation and scale up (a.k.a. Pilot Plants) in manufacturing and packaging

• Analytical development in quality control department

Laboratory or GMP washing??

Fields of applications

Items to be processed

Same equipment and tools for all pharmaceutical

forms that need to be cleaned:

• Glassware (erlenmeyer flasks, volumetric flasks,

pipettes)

• Nalgene bottles

• Shovels, spatulas, stirrers

• Containers, drums

• Tools (funnels, buckets, scissors, etc.)

• Balances

• Trays

Formulation Filling Finishing

Raw material is mixed in one or several steps



Solid by mixing only or

by granulation with a

solvent or liquid :

- Filter housing

- Tanks

- Tri clamps

- Valves

- Grinders

Liquid and Semi-Liquid

forms by mixing only:

- Shipping vessels

- Pressure cans

- Flexible hoses

- Stainless steel tubes

- Manifolds

− Pumps

− Valves

− Hoppers

− Manifolds

− Pistons

− Different parts of the production machines

− Active Parts: Punches, pistons,trays, etc.

− Tools used to dismantle the machines



Tablets / Capsules



Filling and Finishing made in one step

Liquids/injectables:

ampoules, vials, bottles

• Clean glassware before being sterilized and/or filled (bottles, vials) for Injectables

• Different active parts of machines :

-Pumps

-Valves

-Hoppers

Semi-solids:

tubes, plastic strips

- Injection needles

- Manifolds

- Pistons

- Trays

• Other parts of the production machines

• Tools used to dismantle the machines



Primary packaging area:

Types:

- Plastic tubes

- Blister packs

- Strip-seals

To be washed:

- Hoppers

- Conveyors

- Guides

- Slides

- Other parts of machine

- Tools etc.

GMP AND LAB WASHERS

Different designs for different cleaning

requirements

What is a GMP compliant washer-dryer?

Traceability of

construction materials

and operations

Compliant to applicable

regulations (ASME-BPE,

21 CFR part 211, etc.)

Quality of surfaces, welds,

connections, components

Accurate monitoring of all

critical parameters

Design philosophy: NO WATER RETENTION + ALL DOCUMENTED

Hydraulic design

GMP WASHER LAB WASHER

Orbital welding used for piping (no

retention due to weld seams)

Dead legs ratio of 3D for piping

Water feeding pipe sloped to chamber

High grade sanitary recirculating pump

No orbital welding – piping may be

square/rectangular or even flexible hoses

No specified ratio for dead legs

Use of flexible hoses + threaded

connections for water connection

Industry standard pump meant for

extensive & intensive use

Different racks/baskets


Mechanical design

INTERNAL welding of chamber

Weld polishing with Ra < 0.6 µm

All high-grade 316L stainless steel

including outer panels

Use of air-actuated sanitary valves for

air & water

No drain pump – gravity drain only

EXTERNAL welding of chamber

Weld polishing not applicable

316L stainless steel used for chamber

only

Use of electrical valves for water

Drain pump = standard

Gravity drain = option


Chamber construction

Polished weld Non-polished weld

Control system

Use of 21 CFR part 11 compliant PLC

Siemens S7 PLC (most popular) and

Rockwell AB PLC

Possibilites of data exchange table (eg.

SCADA type), data recording & collection

No requirement for electronic signature

or any similar kind of compliance

Mostly simple PCB controlled equipment

Data recording and collection only via

printer


Control system


GMP WASHER IMPORTANT CHARACTERISTICS

GMP washer-dryers important

characteristics

GEW cGMP washer functions

TACT cleaning methods

4 cleaning methods

1. TIME: Wash exposure period

2. ACTION: Mechanical impingement

provided by main pump

3. CHEMICAL: Appropriate cleaning

solution(s) to break bonds of soil

4. TEMPERATURE: Wash Solution

heated to assist cleaning

GMP Washers are specially designed to

have no retention areas, better surface

finishes, and better materials to

eliminate contamination and cross-

contamination. Providing clean and

DRY products.

Chamber sizes

888 9109

101210 131313

P131820

Pit or floor mounted

Adjustable recipe (wash cycle) overview

The steps are always launched in this order. If the recycling period is not programmed, the next step is automatically tested.

STEP OPTIONS DISPLAYED

Unit Range

Pre

was

h 1

Pre

was

h 2

Pre

was

h 3

Was

h

Rin

se A

Aci

d rin

se

Rin

se B

Rin

se 1

Rin

se 2

Rin

se 3

Rin

se 4

Fin

al r

inse

Sup

er d

ryin

g

Coo

ling

Recycling mm:ss 0-29:59

Water - HWFI/CWFI

Detergent quantity ml 0-9999

Acid quantity ml 0-9999

Temperature °C 0-95

Number 1-9

Conductivity check mS/cm 0-99.0

Conductivity check µS/cm 0-500.0

Period mm 0-90

Temperature °C 0-110

Power

• Pump close-coupled with washer

chamber = maximum efficiency

• Pump outlet vertical (mfr recommended)

Advantage: Significantly higher flow rates

(up to 46% in some cases!)

Water pump

Chamber volume/footprint

• Flexible service access

• Innovative door designs

• « Walk-in » trolleys: space saving

and ergonomic

Footprint

Load side

Unload side

Utilities from top

or either side

Cross-contamination

barrier

Mirror image configurations standard

Service access and utilities

Flexible

service

access

Full side: service (swing-

out electrical)

Full front: service (slide-

out electrical)

Advantage:

Full front OR side service access and flexible utilities locations

• ASME BPE 2009 FULL compliance

• Full traceability

• Components, tubing, fittings

• Surface finishes

• USP Class VI

• Elastomers

• Traceability

• GAMP 5 Guidelines

• Documentation

• Programming

Compliance and standards

• Industry standards utilized:

orbital welding and tri-clamp fittings

• Self cleaning:

piping and components positioned for

complete drainage

• Maximized slopes

• Minimum dead legs

• High surface finish

• No threads

Construction features

Allen Bradley, Siemens, control

systems available

• Various touch screen panel sizes

• Panel mounted printer

• Ethernet data integration

Intuitive GUI screens common

across platforms

Controll system

• Industry standard

• Globally available

• Non-proprietary components

and instruments

• ASME BPE 316L SS components

and piping

• USP Class VI elastomers

• Customer-specified components

available

Components

Documentation

• GAMP 5 guidelines: “life cycle

approach”

• Submittal package for approval

“as-built” TOP documents program

source code

• Electronic standard, paper

available

Documentation

• Square chamber

• Spray arm with sprayball ends, top

and bottom of chamber

• Load capacity with 2-Level

washing

• Larg pump HP, 265 to 315 gpm

flow, vert. outlet

Spray coverage

Different options

• Glass door to load viewing- Visual

• Spray arm rotation monitoring- Process

control

• Pump pressure transmitter- Process control

• Pump mass flow- Process control

Wash monitoring

Delivery:

• Flow into chamber is verified during delivery

• Isolation valve at chamber wall rinsed by

lower spray arm

Monitoring:

• Pressure transmitter

• Conductivity monitoring

• Flowmeter, volumetric delivery

• Mass flow, v/v verification versus water

intake

GEW model features

Basis of design

Drying coverage

Drying path:

• Chamber drying: outside of parts and

glassware

• Column drying: inside of parts and

glassware

• Identical and independent systems

Drying efficacy:

• Temperature (Up to 110°C)

• Flowrate: 170 to 300 cfm = no exhaust

fan necessary

• HEPA filtration (dual)

Drying

Monitoring:

• Independent ∆P of HEPA’s

• Independent RTD’s

• DOP ports standard

• Fans/heaters elec. interlocked

INTELLI-RACK LOADING EQUIPMENT

Racks and baskets

• Modular racks for most common applications

• Easy selection based on size of glassware

• Modules interchangeable on base racks

• Ergonomic handling and storage

• Integral support grids, hold down screens and

sprayballs as necessary per application

Customized racks available with Getinge

parts modeling service

IntelliRack - modular & custom wash racks

Versatile, sanitary, multi-level washing

Design-build method

Parts inventory Create 3D

parts models

Approval

drawing 3D rack model Final product

Getinge

exclusive:

parts modeling

service using

high precision

coordinate

measuring

machine

Capture

geometric data

Modular rack – 4 quadrants

Modular rack base (4 quadrants)

Modular rack base (4 modules loaded)

Rack modules – light and flexible solutions

Pumps assembly module

Unladen weight : 2.3kg

Estimated weight with parts : 3.5kg

Pumps assembly module



Filling line modules

Glass vessel module



Basic module



Hoses module



Glassware, hoses, and flat modules

Modules for every application

Questions

November 27, 2013

THANK YOU

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GMP WASHING FOR BIO-PHARMA PRODUCTION · 2016. 12. 6. · GMP Washers are specially designed to...

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