Professional Documents
Culture Documents
Radisson Bl
Blu Hotel
Hotel,
Cork
Mayy 22nd 2014
Agenda
Cross Contamination Control Using a Risk Based
Approach
} Steps in applying the Risk based approach.
} Risk Identification
} Risk Analysis
} Risk Evaluation
MSD B
Ballydine
ll di (API)
(API):Equipment
E i
t
} Factory 01/Pilot Plant:
} 53 vessels (reactors, extractors, tanks)
} 7 centrifuges (Tolhurst & Heinkel) & 2 Filter Driers
} 4 Rotary Dryers
} Factory 03:
} 25 vessels (reactors, extractors, tanks)
} 2 Cogeim Filter Dryers,
Dryers & 2 Heinkel Centrifuges
} 4 Conical Dryers
} Both Facilities are modular: The outlet(s) of any vessel can be
Applying
y g the Risk based Approach to
Cross Contamination
St 1:
Step
1 Risk
Ri k Identification:
Id tifi ti
The Cross Contamination Hazards are
APIs/Intermediates/Raw Materials
Impurities
By-products
Degradants
Detergents
Solvents
Severity of the
effect
Severity ranking
based on Quantity
Mix-Up
Critical effect
> 1Kg
Retention
Critical effect
0.05 - 1Kg
Mechanical Transfer
Major effect 6
0.01-0.05Kg (10g-50g)
Airborne transfer
Negligible effect
Quantity < 0
0.01Kg
01Kg (<10g)
Definition
Examples
p
Mix Up
Mix-up is defined as
contamination at unsafe levels of
one product with another
Retention
Mechanical
Transfer
Airborne Transfer
Carry-over
y
of p
product in the specific
p
ventilation
Detection
Detection Ranking
How?
Mix-Up
Detectable by procedural
controls, material balances,
analytical testing
Retention
Good Probability
Mechanical Transfer
Low Probability
Maybe detectable by
analytical testing
Airborne transfer
Remote Probability
Unlikely to be caught by
analytical testing at such a
low level
Mix Up:
Defined as contamination at unsafe levels of one product with another.
Examples are charging of the desired material to the wrong equipment, charge of incorrect
material to desired equipment and accidental use of dirty equipment.
E i
Equipment
t Cleaning
Cl
i Validation
V lid ti Programme:
P
} Modular basis using pre-defined cleaning regime
} So
Solvent
e t rinse
se ((where
e e app
appropriate),
op ate), sswab
ab a
and
d visual
sua inspection
spect o
specifications.
} Detailed cleaning procedures are in place
Direct contact of the product with such surfaces as operator apparel and
gloves.
Cleaning Specifications
Pre-defined justified cleaning specifications.
Set based on the Health Based Cleaning
g methodology.
gy
Rinse tested to meet pre-determined specification
Swab testing to meet pre-determined specification 100mcg/25cm2
swab
Vessel visually clean (inspected when dry)
Each New product is confirmed to be within existing specification.
specification
Suitability of the cleaning specifications going into the process step
are confirmed.
confirmed
Calculation of the total carry-over for each contaminant going into the
campaign.
carry-over
over is calculated based on the maximum swab
The worst case carry
specification .
Execution Of Cleaning
Post Campaign Flush (typically with the process solvent or Methanol)
Modular approach - Each equipment module associated with a process equipment
p
y to anyy other module in that train.
train is cleaned separately
Validation status is applied to each module which is uniquely associated with the
process from which the module is being cleaned
Three successful cleanouts of a module are required for a clean-out to be deemed
validated.
Post execution of cleaning
Cleaning
Cl
i validation
lid ti completion
l ti
d
documented
t d as postt execution
ti section
ti off protocol.
t
l
Includes all Laboratory cleaning Results
programme
boxes).
Question
What is the
equipment
classification?
What is the
surface area of
product
contact part?
What is the
potential to
absorb/adhere
product?
Is it easily
Cleaned?
Is it easily
Visually
Inspected?
Final
Rating
Score/Multiplier
40
20
20
15
100
Direct Product
Contact
>50%
High potential
Difficult
Difficult
300
Auxiliary
Component
10-50%
Medium
potential
Moderate
Moderate
200
<10%
Low potential
Easy
Easy
100
Proximity
Area
Dirty
Di t h
hold
ld titime and
dC
Campaign
i L
Length
th where
h
it iis a problem
bl
P C
Pre-Campaign
i Ch
Checks
k
K T
Key
Takeaways
k
Cross Contamination Control is not just equipment Cleaning.
Apply a Risk Based Approach and formally document the Risk
Assessment
Validated
V lid t d E
Equipment
i
t Cl
Cleaning
i Complex
C
l S
System
t
ffor non-
Process Understanding
Detailed documentation
Robust business systems
People with Expertise and Experience
Challenges/Opportunities
Cleaning Verification only?
Reduced Verification Post Cleaning Validation
Turnaround: Time spent in cleaning and set up.
Equipment issues versus cleaning issues
Science of Cleaning Solubility only, Detergents?
Link between R&D and Commercial manufacture
Thank You
Questions?
Q
ti
?