Transcript Sterile Processing - DIT - School of Electrical

CPPT 9010: Facility Design & Operation
D.I.T. DT275
Masters in Chemical and
Pharmaceutical Process Technology
24th November 2009
Clement Farrar
BA BAI MSc MIEI
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Lecture Overview
1) Introduction
 2) Aseptic Processing
 3) Process Stages
 4) Utilities Introduction
 5) Assignment Introduction/ Workshop
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Qualifications
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1998 - 2002: B.A., B.A.I. - Mechanical &
Manufacturing Engineering, TCD
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2002 - 2003: M.Sc. - Bioengineering, TCD
Work Experience
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2003 - Present: Wyeth BioTech (now Pfizer),
Grange Castle, Clondalkin
2003 - 2008: Process Engineer - Drug Substance
Start Up to Commercial Production
 2009: Process Engineer - Syringe Fill Finish Start
Up
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Wyeth At A Glance
 Founded
in 1860 by two Wyeth brothers in Philadelphia
 Became American Home Products Corporation in 1926
 Changed to Wyeth in 2002
 Corporate
headquarters – Madison, New Jersey
 2008 Sales
– $22.8 billion
 Approximately
47,400 employees worldwide: 22,600
U.S. and 24,600 international
 2009 –
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Became part of the Pfizer
Wyeth Pharmaceuticals’ Leadership
Positions
#1 Antidepressant
#1 RA & Psoriasis Biologic
#1 Vaccine
#1 HRT
#1 I.V. Antibiotic
#1 Hemophilia B
#1 Infant Formula (In Aggregate Market Where We Compete)
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Ireland’s Pharmaceutical
Industry… Then and Now
1973
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Exports less that €100 million
Employment less than 2000
Ireland’s Pharmaceutical
Industry… Then and Now
Exports €16.7 billion – Largest net exporter of
pharmaceuticals in the world
Employment 24,500 - 2 out of every 5 pharmaceutical
jobs created in Europe in 2008 were in Ireland - 50%
hold a third level qualification
2008
120 companies including 13 of the top 15 worldwide
Replacement value of the investment by the pharma
sector in the Irish economy exceeds €40 billion – €3
billion in Corporation Tax
€7 billion invested in last nine years
1973
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Exports less that €100 million
Employment less than 2,000
Why Ireland?
 Availability of
fully serviced 90 acre site
 Quality and availability of workforce
 Support from Government, IDA Ireland and South
Dublin County Council
 Corporation Tax regime in Ireland
 Focus on Research in Ireland
 35 years of manufacturing experience in Ireland.
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Once a muddy field in Clondalkin…
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Now… A Centre of Biotechnology
Excellence
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Grange Castle At-A-Glance
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Largest capital investment ever undertaken by Wyeth
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1,224 full time employees and 220 contractors
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Producing some of the world’s top medicines
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The anchor for the establishment of a biotechnology
cluster in Ireland
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One of the largest biotech campuses in the world
Aerial View of Grange Castle
Drug
Substance
Central Utilities
Building
Product
Development
Centre (PDC)
Warehouse
Syringe
Fill/Finish
Vial
Fill/Finish
Vaccine
Conjugation
Quality & Administration
Building (QA/QC)
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Grange Castle Products
The first advance in 20 years
for the treatment of
moderately to severely active
rheumatoid arthritis (RA) in
adult and juvenile patients
Antibiotic – for the
treatment of
complicated intraabdominal infections
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PneumococcalMeningicoccal Vaccine
Relistor is a new product,
which will be used for the
treatment of opioidinduced side effects,
including constipation
and post-operative bowel
dysfunction.
Recruitment

80,000 job applications to date

25,000 Interviews conducted to date

1,224 full time employees in place today

220 full time contractors
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11% of employees relocated from international locations
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Half of this group are Irish people returning home
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95% with third level qualifications
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55% male; 45% female
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Average age 37
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Aim of Module
Experienced Process Engineer working in the
industry
 Invite any Questions I may be able to answer
from my experience
 Assignment - aim is to try to get you thinking
in a real life ‘facility design’ frame of mind
 Give you as much knowledge/ experience to
allow you use your skills & knowledge
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Facility Design & Operation
1) Introduction
 2) Aseptic Processing
 3) Process Stages
 4) Utilities Introduction (inc HVAC)
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Learning Outcomes
At the end of this Lecture you should be able to …..
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Describe what is meant by Aseptic Processing
Define what is meant by a Critical Process step
Define types and sources of Contamination in Aseptic operations
Describe how contamination risk is minimised
Describe key factors influencing facility design
Describe the process steps in a typical Aseptic process
Define the area Classification Requirements for typical process
steps
Describe what is meant by ‘Direct’ and ‘Indirect’ impact utility
systems
Sterile Processing
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Parenteral Drugs:
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Injectable drugs bypass the body’s natural defences so must be sterile
Terminal Sterilisation:
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Sterilise drug in final container (after manufacture and packaging)
Preferred method of sterilisation
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Many drugs not suitable for this method of sterilisation
Aseptic Processing:
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Moist Heat Sterilisation
Gamma Radiation
E-Beam
Microwave
Individual components are sterilised separately and brought together in
the final form in a sterile environment.
Aseptic vs. Sterile
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Definition of Aseptic
“Free of or using methods to keep free of Pathological
Micro-organisms” synonym : sterile
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Sterile processing area is also know as the
Aseptic Processing Area, Critical Processing
Area or Sterile Core.
Aseptic Facility Design
Aseptic
Processing Area
Area where critical process steps carried out
Critical Process Steps
Activities during which the sterilised product and container
/ closure are exposed to atmosphere
Design must minimise challenge to Aseptic Processing
Area – HOW?
Flow of raw materials, components, drug product containers,
closures, in-process materials, drug products and people through
the facility shall be designed to prevent contamination.
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Contamination – Types & Sources
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Non-Viable (Particulates) including Endotoxins
 Sources:
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Equipment, Clothing, Water, Air
Viable (Micro-Organisms)
 Sources:
Equipment, People, Water, Air, Tools,
Excipients, Active Ingredients
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Contamination – Preventative Measures
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Non Viable:
 Contact
Parts are cleaned and sterilised
 Water is purified
 Air is HEPA Filtered
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Viable:
 Interventions in
sterile core are minimised
 Solutions are sterile filtered through a 0.2m filter
 Air is HEPA Filtered
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Design concept to minimise challenge to
Aseptic Processing Area
Fig 2.1 Nested Manufacturing Zone (ISPE Guideline Vol 3)
Nested Manufacturing Zones (Diagrammatic Product: Out-Flow Not Shown
External Areas
Street, Offices, Restaurant
Transition Zone
Brings People, Materials etc., from External Areas to the
Manufacturing Areas in a ‘Controlled’ Manner
Clean Area
Provides a Protective Envelope to Minimise the
Challenge to the Critical Areas
People
Change
Change
Critical Processing
Area
e.g. Point of Fill
Sterilise
Remove
Outers
Container Closures
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Compounding
Remove
Outers
Raw
Materials
Aseptic Facility Design
Fig 2.2 Sterile Manufacturing Flowchart (ISPE Guideline Vol 3)
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Highlights interdependence of operations in support of the core sterile activity
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Highlights importance of support area design to GMP Compliance of Aseptic Processing Area
Sterile Manufacturing Flowchart
People
Services
Materials
Actives
+
Excipients
Gowning
Container /
Closure
Equipment
Components
Air /
Gases
Water /
Liquids
Control of Flows Into Aseptic Area
ASEPTIC PROCESSING AREA
Cleaning /
Sterilisation
Cleaning /
Sterilisation
Terminal Sterilisation?
Control of Flows Out
of Aseptic Area
Waste
Clothing
Materials
Dirty Equipment
Components for
Re-Use
Effluents
PRODUCT
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Exercise 1
You are members of a project team designing a new
sterile product (s) facility –
Discuss what product / process information you
would need to ensure the facility can handle this
new product
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Exercise Answer
Key Factors Influencing Facility
Design
 Product
 Form - liquid/ powder
(lyopholised)
 Product Characteristicslight sensitive/
Excipients- number,
quality, form, hazards
etc.
 Presentation- vials/
syringes
 Market- market need,
regulatory requirementsIMB/ FDA
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Exercise Answer
Key Factors Influencing Facility Design
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Process
Degradation with thermal sterilisation?
 Process duration - will impact production capacity
 Cross Contamination Issues - e.g. strong antibiotics
 Current Facility Capacity - spare capacity or shortfall
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