Sterile Processing

drawerbeamerBiotechnology

Dec 6, 2012 (4 years and 17 days ago)

340 views



1




CPPT 9010: Facility Design & Operation

D.I.T. DT275


Masters in Chemical and

Pharmaceutical Process Technology

24
th

November 2009


Clement Farrar

BA BAI MSc MIEI



2




Lecture Overview


1) Introduction


2) Aseptic Processing


3) Process Stages


4) Utilities Introduction


5) Assignment Introduction/ Workshop




3




Qualifications



1998
-

2002: B.A., B.A.I.
-

Mechanical &
Manufacturing Engineering, TCD



2002
-

2003: M.Sc.
-

Bioengineering, TCD



4




Work Experience


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




5




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


Became part of the Pfizer



6




#1 Antidepressant

#1 RA & Psoriasis Biologic

#1 Vaccine

#1 I.V. Antibiotic

#1 Infant Formula
(In Aggregate Market Where We Compete)

#1 HRT

#1 Hemophilia B

Wyeth Pharmaceuticals’ Leadership
Positions



7




Ireland’s Pharmaceutical
Industry…
Then

and Now

1973

Exports less that

100 million

Employment less than 2000



8




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



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

Exports less that

100 million

Employment less than 2,000

2008

Ireland’s Pharmaceutical
Industry… Then
and Now



9




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
.





10




Once a muddy field in Clondalkin…



11




Now… A Centre of Biotechnology
Excellence



12




Grange Castle At
-
A
-
Glance


Largest capital investment ever undertaken by Wyeth


1,224 full time employees and 220 contractors


Producing some of the world’s top medicines


The anchor for the establishment of a biotechnology
cluster in Ireland


One of the largest biotech campuses in the world



13




Aerial View of Grange Castle

Product
Development
Centre (PDC)

Vial
Fill/Finish

Syringe
Fill/Finish

Warehouse

Drug
Substance

Quality & Administration
Building (QA/QC)

Central Utilities
Building

Vaccine
Conjugation



14




Grange Castle Products

Relistor is a new product,
which will be used for the
treatment of opioid
-
induced side effects,
including constipation
and post
-
operative bowel
dysfunction.

Pneumococcal
-
Meningicoccal Vaccine

Antibiotic


for the
treatment of
complicated intra
-
abdominal infections

The first advance in 20 years
for the treatment of
moderately to severely active
rheumatoid arthritis (RA) in
adult and juvenile patients



15




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



11% of employees relocated from international locations



Half of this group are Irish people returning home



95% with third level qualifications



55% male; 45% female



Average age 37




16




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



17




Facility Design & Operation


1) Introduction


2) Aseptic Processing


3) Process Stages


4) Utilities Introduction (inc HVAC)




18




Learning Outcomes

At the end of this Lecture you should be able to …..



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




19




Sterile Processing


Parenteral Drugs:



Injectable drugs bypass the body’s natural
defences

so must be sterile


Terminal Sterilisation:



Sterilise drug in final container (after manufacture and packaging)


Preferred method of sterilisation


Moist Heat Sterilisation


Gamma Radiation


E
-
Beam


Microwave


Many drugs not suitable for this method of sterilisation


Aseptic Processing:


Individual components are sterilised separately and brought together in
the final form in a sterile environment.




20




Aseptic vs. Sterile


Definition of Aseptic

“Free of or using methods to keep free of Pathological
Micro
-
organisms” synonym : sterile



Sterile processing area is also know as the
Aseptic Processing Area, Critical Processing
Area or Sterile Core.



21




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.




22




Contamination


Types & Sources


Non
-
Viable (Particulates) including Endotoxins


Sources: Equipment, Clothing, Water, Air



Viable (Micro
-
Organisms)


Sources: Equipment, People, Water, Air, Tools,
Excipients, Active Ingredients



23




Contamination


Preventative Measures


Non Viable:


Contact Parts are cleaned and sterilised


Water is purified


Air is HEPA Filtered


Viable:


Interventions in sterile core are minimised


Solutions are sterile filtered through a 0.2

洠晩汴敲


Air is HEPA Filtered



24




Design concept to minimise challenge to
Aseptic Processing Area

Fig 2.1 Nested Manufacturing Zone (ISPE Guideline Vol 3)

Clean Area
Provides a Protective Envelope to
Minimise
the
Challenge to the Critical Areas
External Areas
Street
,
Offices
,
Restaurant
Transition Zone
Brings People
,
Materials etc
.
,
from External Areas to the
Manufacturing Areas in a ‘Controlled’ Manner
Change
Critical Processing
Area
e
.
g
.
Point of Fill
People
Change
Compounding
Remove
Outers
Raw
Materials
Remove
Outers
Sterilise
Container Closures
Nested Manufacturing Zones
(
Diagrammatic Product
:
Out
-
Flow Not Shown


25




Aseptic Facility Design

Fig 2.2 Sterile Manufacturing Flowchart (ISPE Guideline Vol 3)


Highlights interdependence of operations in support of the core sterile activity


Highlights importance of support area design to GMP Compliance of Aseptic Processing Area

Effluents
Materials
Clothing
Waste
Equipment
Components
Container
/
Closure
Actives
+
Excipients
Materials
Water
/
Liquids
Air
/
Gases
Services
Gowning
People
Dirty Equipment
Components for
Re
-
Use
Cleaning
/
Sterilisation
Cleaning
/
Sterilisation
PRODUCT
Control of Flows Out of Aseptic Area
Control of Flows Into Aseptic Area
ASEPTIC PROCESSING AREA
Terminal Sterilisation
?
Sterile Manufacturing Flowchart


26




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



27




Exercise Answer

Key Factors Influencing Facility
Design


Product


Form
-

liquid/ powder
(lyopholised)


Product Characteristics
-

light sensitive/
Excipients
-

number,
quality, form, hazards
etc.


Presentation
-

vials/
syringes


Market
-

market need,
regulatory requirements
-

IMB/ FDA




28




Exercise Answer

Key Factors Influencing Facility Design



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