ISPE NJ Chapter
Tour Demo of Aseptic Filling Line
Tour-Demo
with
Validation Workshop
Dragutin Stoicovici
Director of Quality Assurance
February 16, 2011
Dragutin Stoicovici, Dir. of QA
www.cozzoli.com
Technology
h l
Review
i
• Pharmaceutical, Cosmetics, Biotech
Products
• Aseptic Packaging
• Clean Room
• cGMP
Dragutin Stoicovici, Dir. of QA
Requirements
i
•
•
•
•
Dragutin Stoicovici, Dir. of QA
Equipment Requirements
FDA/USDA Expectations
p
cGMP Requirements
Validation
Terminology
i l
• Endotoxin – a toxin produced within a
microorganism
• Pyrogen
P
– a substance
b
that
h produces
d
ffever.
Endotoxins are pyrogens.
• Log
L Reduction
R d ti – reduction
d ti off Endotoxin
E d t i or
Biological indicator (1Log=10 times less,
2Log=100
2Log
100, 3Log=1000
3Log 1000…))
Dragutin Stoicovici, Dir. of QA
Terminology
i l
• A
Aseptic
i Core
C
– area requires
i special
i l
gowning
• Washroom
W h
– vials
i l washed
h d andd
delivered for sterilization (oven or
tunnel)
• Fill Room – vials are filled with drug
product and then closed
Dragutin Stoicovici, Dir. of QA
Aseptic
i Fill
ill Line
i
•
•
•
•
•
Dragutin Stoicovici, Dir. of QA
Vial Washer – class 10000/100000
Sterilizer, Depyrogenation
py g
Tunnel
Filler – class 100
Closing: Plugger,
Plugger Capper,
Capper Stoppering
Crimping – class 10000
Containers
i
•
•
•
•
•
•
Dragutin Stoicovici, Dir. of QA
vials
bottles
ampules
syringes
IV type bags
Special…
Product
d
• Liquid – flammability, density,
viscosity, suspension…
• Powder – humidity, static charge,
pparticle shape
p and size
• Tablets
Dragutin Stoicovici, Dir. of QA
Washing
hi Equipment
i
Vials, Bottles, Ampules, Stoppers
• Batch
• Automatic
Dragutin Stoicovici, Dir. of QA
Filling
illi Equipment
i
Liquid, Powder
• Semiautomatic
• Mid Range – Intermittent
• High Speed – Continuous
• Inline
• Rotary
Dragutin Stoicovici, Dir. of QA
Liquid
i id Filling
illi Methods
h d
•
•
•
•
•
Dragutin Stoicovici, Dir. of QA
Piston Pump
Diaphragm Pumps
Peristaltic Pump
Mi
Micro
Fill
Fillers (IVEK)
Time Pressure
Closing
l i Equipment
i
Ampules, Stoppering, Plugging,
Capping
• Semiautomatic
• Intermittent
• Continuous
C i
Dragutin Stoicovici, Dir. of QA
Monoblock
bl k Equipment
i
Ampules, Stoppering, Plugging,
Capping
• Fill, Seal Ampules
• Fill, Plug, Cap
• Fill, Stopper
Dragutin Stoicovici, Dir. of QA
Ancillary
ill
Equipment
i
Ampules, Stoppering, Plugging,
Capping
• Unscramblers
• Conveyors
• Bottle Trayers
Dragutin Stoicovici, Dir. of QA
Before you start…
Ri k Based
Risk
B d Approach
A
h
Dragutin Stoicovici, Dir. of QA
h //
http://www.youtube.com/watch?v=IFFvATEW6dM
b
/
h? IFF ATEW6dM
VIDEO
Dragutin Stoicovici, Dir. of QA
Vhat is Validation?
“Establishing
“E
bli hi documented
d
d evidence
id
which provides a high degree of
assurance that a specific process will
consistentlyy pproduce a product
p
meetingg
its pre-determined specifications and
quality attributes.
attributes ”
Dragutin Stoicovici, Dir. of QA
Require Documentation:
-Customer Specification (May include SOP’s)
-Manufacturer’s Proposal
-Purchase
Purchase OrderOrder do not need the dollar amounts
-Order Acknowledgement
-Customer component drawings
-Electrical Schematics/Drawings
-All
All drawings provided for the equipment.
equipment An index of drawings only,
only
will be acceptable.
-Cut Sheets for components utilized in the manufacturer of the
equipment
-Material
Material Certification for product contact and exposed parts.
parts
Certification must include which parts were manufactured from the
materials.
-Passivation reports (where Passivation is required)
-Electropolish reports (when electropolish is required)
-Bill of Material, listing component manufacturer, model no, type, etc.
-Operator interface screens
-Ladder Logic (where PLC is utilized)
Dragutin Stoicovici, Dir. of QA
Title page
Equipment
Location
Protocol
Dragutin Stoicovici, Dir. of QA
Approvals
Author
Blank Protocol Approval
Fi l Protocol
Final
P t l Approval
A
l
Dragutin Stoicovici, Dir. of QA
Each Section
Purpose
Scope
Dragutin Stoicovici, Dir. of QA
Certification
…to the best of
executor s knowledge
executor’s
knowledge…
If the executor is not
qualified in a specific
area then qualified help
shall
h ll be
b used.
d
Dragutin Stoicovici, Dir. of QA
System description
Introduction
Process Definition
Dragutin Stoicovici, Dir. of QA
System description
…more…
Process Definition
Dragutin Stoicovici, Dir. of QA
Instructions
to be followed when
executing the
protocol and …
Dragutin Stoicovici, Dir. of QA
Responsibilities
assigned
Dragutin Stoicovici, Dir. of QA
Acceptance Criteria
G id d by
Guided
b the
th Instructions
I t ti
and using the Method, the
acceptance needs to be
confirmed. Any deviation
will be noted and a course
of action initiated.
Dragutin Stoicovici, Dir. of QA
Check List
This is the script for executing the
protocol. Each item will be accepted
or rejected, if there are multiple
methods of verifying, then specify
method, and always initial and date.
Also at the bottom of each page note
any comments and the persons that
completed and verified sign and date.
date
Dragutin Stoicovici, Dir. of QA
IQ Check List
-Equipment and Instrument Check list
-Documentation
Documentation
-Drawings, Schematics and
Component Identification
-Supporting
Supporting Utilities
Dragutin Stoicovici, Dir. of QA
OQ Check List
-Instrument Calibration
-Operator Interface
-Manual and Automatic Controls
-PLC
PLC Logic and Controls
-Alarms
-Fill Weight Verification (or other critical
parameters)
-Capping Verification
Dragutin Stoicovici, Dir. of QA
PQ Check List
-Reference (Any relevant SOPs)
-Process Instruments
-Media Fills
-Cap Seal Integrity
-Capping Application (torque)
Dragutin Stoicovici, Dir. of QA
PQ Check List
As IQ is very generic in relation to the
process, the OQ becomes more specific
involving specific groups of people
(operators) and SOPs, and the PQ is totally
dependant of the specific process.
Dragutin Stoicovici, Dir. of QA
Summary of Results
The acceptance criteria of
every section will be listed
here together with the result.
here,
result
Dragutin Stoicovici, Dir. of QA
Exception Report
All Exceptions are captured in
this section. This is done every
time an acceptance criteria can
not be fulfilled.
Dragutin Stoicovici, Dir. of QA
Exception Report
A protocol execution is
successful only after each and
every one of the exceptions
have been corrected.
Dragutin Stoicovici, Dir. of QA
The End …
Dragutin Stoicovici, Dir. of QA
…well, this is just the beginning.
Once the equipment has been
successfully validate, all changes
shall be made under change
control.
control
There also is a regular
revalidation cycle, every 6 month
(or a year) as dictated by your
SOP.
Dragutin Stoicovici, Dir. of QA
The end of the validation effort
will come only when the
equipment has reached it’s end
of life and it’s decomission has
been completed.
Dragutin Stoicovici, Dir. of QA
References:
21 CFR Parts 210 & 211
21 CFR Part 11
GAMP
cG
cGMP
USP 24 <1211> - Sterility
USP 24 <85> - Biological Test, Bacterial Endotoxin Tests
www . fda . gov
www . ispe
p . orgg
Dragutin Stoicovici, Dir. of QA
Thank you
y
Dragutin Stoicovici, Dir. of QA