Transcript Welcome to my graphical Knowledge summary

Welcome to my graphical
Knowledge summary
Dussex Jean-Charles Via pizzamiglio,9 CH-6833 Vacallo [email protected]

Summary of system actors
TQMS-1

Presentation in Work breakdown structure style
TQMS-1

Procedure deviation process according to deviation criticality
Approved PDR
Report deviation
Assess impact
PROCEDURE
DEVIATION
Impact
11 12 1
2
10
9
3
8
4
7 6 5
on product quality
BATCH
RELEA
SE
Minor
Includes
PDR
references
Before batch release
In parallel
major
LOT
INVESTIGATION
11 12 1
2
10
9
3
8
4
7 6 5
Open a Change report
or fill in already open CHR
immediately
Other batches to be
manufactured ?
LIR
decision
Batch
destination
and changes to be applied
LIR
are taken in LIR decision
CHR
Yes
Approved PDR
11 12 1
2
10
9
3
8
4
7 6 5
REJECT
ED
Reprocess
ASAP
Examples of
Processes Scenario
CHR
BATCH
Includes
RELEAS LIRreference
E
s
Customer
TQMS-2
Wait until a reasonable number
of minor changes are to be applied,
and or validation process occurs
Normally during annual review
process
Attached to the MBR as
manufacturing instruction
FOR PLANNED DEVIATION
BATCH
RELEA
SE
Includes
PDR
references
Apply change
Process parameter design space
CRITICAL PROCESS PARAMETER
Ensure product Quality
Design space
Recommended Process parameters
Used for proces
optimisation
Development
report
May be
updated
Operational
process
parameter
May be
updated
Operational
process
parameter
Working parameter range
Reported in DMF
Rpoted in Batch card
MBR
Significant process
parameter
Critical
Significant process
parameter
Instruments calibration range
Process limit for product quality
TQMS-3
CRITICAL PROCESS PARAMETER

Critical

Validation workflow
Development
studies
Process
development
Process and Product
characterisation
Risk Assesment
Process & Product
Characterisation
Report(s)
Manufacturing
equipment
capability
Scientific
Judgement
Define Critical and
Key Operational
Paameters and their
Ranges
Define critical
product & Proces
attributes
Updated Process
Understanding
Process Development Report(s)
Process
Validation
Master Plan
Process
Potocols
Link to Qualification
Activities:
Equipmnt, Utilities,
Facilities, raw Materials
Production
Records
Manufacture
Conformance
Lots
Process
Validation
Reports
TQMS-4
Prior manufacturing
Experience
Process
qualification
phase
Commercialisation
phase
Ongoing
Process
Monitoring
PROCESS DESIGN
PHASE

Filter dryer Failure Mode Effect Analysis-01
Risk analysis

Cause Effect Diagram: sampling sys. no powder transferred
Risk analysis

Process transfer and Equipment qualification
Process transfer
Some concepts

Example of Room layouts and symbols
Personnel in
Trafic zone
Some room
characteristic
symbols
Class
C
D
N
Personnel clothing steps
Pressure
+++
++
+25/-30 pA
+25 pA
+ +10/-15 pA
---
--25/-30 pA
--
-20 pA
-10/-15 pA
Personnel flow, room pressure and class

Factory entrance
Factory personnel entry from 008 to corridor
022
IN Steps
Symbol
Local
Description
1
007
Inizia la procedura d’entrata
personale
Personnel entry procedure
start.
2
010 & 011
Toglie giacca, zaino etc…
Mette scarpe per aree di
servizio e commune a tutto lo
stabile
Status
Qui si segrega le vie per personale ufficio, laboratorio, magazzino etc..
il personale di produzione segue la via step 3 e succsessivi
NonProduction
Staff
PRODUCTION
STAFF
Personnel flow

Class D surrounding area
3
Corridor
012 & 013
4
012 & 013
Mette le calze di nylon (usa e
geta) e le scarpe di
produzione
lascia qui tutti gli ogetti non
amessi in area produttiva.
Mette I vestiti di produzione:
- pantaloni bianchi
- Maglitta bianca
- Camice bianco
Accede al corridoio 015 ed al
Sas 018
ACCESS CONTROL
1
AUTHORISED
PERSONNEL
ONLY
5
6
Personnel flow
018
Desinfetta le mani, passa
sas 016 ed accede ai
corridoi di produzione 022
028, 029 , lift, 129, 128,121
Personnel is now able to travel in Class D corridors
and access to Sas entry of the manufacturing boxes

Specific workplace in qualified room
Personnel access to BOX 023
IN Steps
Local
Description
023-1
Enter to sas 023-A
Smette il camice
bianco.
023.2
From 023-A to 023
Indossa il
camice verde
Sovra scarpe e
cuffia ?
023.3
Work in 023
Out steps
Symbol
Symbol
Status
Flow
023.4
From 023 to 023-A
023.5
023-A
Smette il camice
verde
Sovra scarpe e
cuffia ?
023.5
From 023-A to
corridor
Indossa il
camice bianco
Personnel is now able to travel in Class D corridors and access to
Sas entry of the manufacturing boxes or to return to civil clothing area.
Personnel flow

Water system 090320
Factory planning-P26

Chromatography system pre-layout
Pre-URS discussion for project definition

Chromatography system Project pre-layout phase 1
Pre-URS discussion for project definition

Drawing symbols (CAD)
P and ID symbols 110303

Development and test of new drying concept/components
1
FILTRATE
U
SL
Load slurry
RR
In order to develop new
concepts/components to be applied
in filtering/drying applications, we
test, using a simple PE Bucket:
• New discarding valve (SAV)
• New filter sinter plate
• Pneumatic conveying of dried
product.
•New discarding cyclone
VACUUM
NITROGEN
Y
2
°c
NITROGEN
OUTLET
VACUUM
<
Dry
3
OUTLET
Move cake
Well Done.
VACUUM
After results computing, we
decide to proceed with
integrations of the
concept/components to the
entire range of filters/dryers we
are using or prototyping.
OPEN VALVE
NITR
4
OGE
N
NITROGEN
Discard
OPEN VALVE
Transfer
system
Final
container
Filter dryer flow inversion static drying

Filter dryer-NEW study of critical contamination points
Filter dryer flow inversion drying tray model
Filter dryer-NEW study of critical contamination points

Filter
Wash
P-18
Vacuum oven
Vacuum oven
Vacuum oven
Vacuum oven
Vacuum oven
Product
data label
E-2
Filter and wash
Transfer in drying container, Weigh
Close oven
Small pressure/
equilibrate level
Apply vacuum
P-24
Product suction
Open valve
Sample
Open and
close oven
Dry
Appply vacuum
Finish
Drying
Remove from Oven, weigh and
take sample
Transfer to final
container
Apply vacuum
Break vacuum
Stop or contain
pipe end
Close and
clean final
container
Break vacuum
Exit of the
contaminated
area
Apply label,
weigh….
Conect
final
container
Continue
drying/sampling
up to OK
Close the
valve
Open valve
Close valve
Suction sampling
Stop or contain
pipe end
P-33
Conect
final
container
P-51
P-45
P-44
P-50
Product contained in dirty enclosure
Product contained in dirty enclosure
Product in contact with area area
Product in clean enclosure
External enclosure not contaminated
External enclosure contaminated
AREA contaminated
External enclosure not contaminated
Minor risk of contamination
Risk of contamination
Risk of contamination
No contamination risk
Filter dryer flow inversion static drying container

Schematic flow of drying operations
Sampling Operation
V-1
V1
V2
SAV
Sequence
Sampling 1
2,1, sav
Sampling quantity OK
Sav, 2, 1
Loose a little bit sampling container
SAV
m
Mount a new container
At mounted container
V-2
Further samplings, repeat the 5 above steps
Decontamination / cleaningOperation
V1
V2
SAV
Sequence
The flushing connector
2,1, sav
At mounted flushing connector
Sav, 2, 1
Fluch decontamination medium
m
At decontamination OK
Disconect the lateral TC onto the sampling tee
Stop the lateral TC
Close V-1
Disconnect V-1
Disconnect the flushing connector
Brouh the tee as is into a glove box in order to dismount it and decontaminate the superior part included the contaminated filter.
Alternatively, depends of further planned operations, disconnect at the point wher flexible fit the SAV
V-1
SAV
V-2
Note, the points of potential contamination can be covered by mounting a plastic bag
as enclosure. The bag will be closed during the vacuum suction phase applied for
disconnecting operations. The bag enclosing the disconnected part is used as
contamination barrer and will be removed only in a protected area (GB for high active,
laminar flow or other area according to product needs.
Filter dryer flow inversion ancillary equipments

Filter 8 inch modified for integration in glove box model 2
Filter Dryer modules with sampling

Filter 8 inch modified for integration in glove box model 3ed2
Filter Dryer modules with sampling

Filter glass DN-150 with heating
Layout of filter dryer with in line heater unit.
Integrated mass flow controller and flash
heating assembly
ST-2
FP-3
FP-2
FP-1
V-1
ST-1
FP-2
FP-4
FP-5
FP-6
FP-7
V-2
Filter dryer DN150 based

Glass reactor units, skid mounted into glove boxes P-13
FACE
799
R4A
BOX-3
T6A
R3A
R6B
T6B
BOX-2
R4B Gs1
1499
670
744
1398
BOX-1
856
PLAN
Containment glove box-P13

Reactor Skid and special vacuum line
BOX 3 Unit
BOX 2 Unit
Flex to
G1/2” male
IF2A
R4A
T6A
R3A
R6B
Containment glove box-P13
T6B
R4B Gs1

Filter 10 inches in glove box, pre-layout
STATIC FILTER
TOP VIEW
OPTIONAL STIRRED
FILTER
Containment for filtering/drying

Clostridium high contamination risk lab layout ed2
“Nursery”
Area
P: ------
Reactors area
P: ------
Product separation
area?
P: ------
Material and products
decontamination area
P: ------
QC area
P: ------
Pressure
Surrounding area 2
P: ---
Intermediate Sas
material and
equipment
P: Wall
SAs
+++
++
+25/-30 pA
+25 pA
+ +10/-15 pA
---
--25/-30 pA
--
-20 pA
-10/-15 pA
Wall
autocalve
“Kitchen”
P: ++
Personal in
changing
room 2
P: ++
Personal out
decontaminati
ion
-----P:
Personnal
Personal out
RM non cotaminated
Changing
decontaminati
in
room 1 in and
ion-2
++
P:++
out
P: ---++
P:++
Surrounding area 1
+++
P: +++
Containment area for biotech
Product out
decontaminati
ion 2
P: ++
Product out
out 3
P:++++

Layout -1 with one outlet candle filter
P-72
P-36
CIP
Process N 2
MFC
CIP
P-28
F-1
V-1
Assigned to
Sparger
Pressure sensor
Reserve/CIP out
CIP in to sprayball
Gas out+PT100
Sigght glass and related light
Sampling or resserve port
Product filling
Description
Custom made with sinter
Pressure sensor PLC connected to PLC
PT-100 connected to PLC
Light to PLC
PLC to mange signal ?
PLC
Flow
X
?
?
x
x
?
Valves
V-1
V-2
V-3
V4
V5
V-6
V-7
V-8
V-9
Assigned to
Cip IN
Cip iN
Cip IN
Process gas in
Process gas in
Gas out
Gas out
Process gas in
Gas out
Description
Pneumatic actuated membrane valve
Pneumatic actuated membrane valve
Pneumatic actuated membrane valve
Pneumatic actuated membrane valve
Pneumatic actuated membrane valve
Pneumatic actuated membrane valve
Pneumatic actuated membrane valve
Check valve
Check valve
PLC
x
x
x
x
x
x
x
x
x
Item
NH
MFC
CIP
PL-1
Assigned to
Nitrogen heater
Mass flow controller
?
Pneumatic lift
Description
PLC
x
x
?
Item
P-1
P-2
P-3
P-4
P-5
P-6
P-7
P-8
Nitrogen heater
NH
P-28
V-2
V-8
V-3
.
°C
Exhaust gas
V-9
V-6
V5
V4
V-7
PI
LI
CIP
P-8
P-1
P-6
P-3
P-4
P-2
P-5
P-7
SG
Port
Assigned to
P-1
Sparger
P-2
Pressure sensor
P-3
Reserve/Cip out?
P-4
CIP port in
P-5
Gas out+ Pt100
P-6
P-6
P-7
P-7
P-8
Product filling
PL-1 Pneumatic lift
Connector
Ancilliary
Internal TK 1-1/2”
Mass flow + Heater+PLC
TC 1-1/2 or NW 32 OVP+PLC
TC 1-1/2 or NW 32 Sensor+PLC
TC 1-1/2 or NW 32 CIP
TC 1-1/2 or NW 32 TC 1-1/2 or NW 34 or TK
Eventual sight glass+ light
Eventual sampling port
PlC safety durig opening
PlC safety durig opening
Automated micro powder dryer-P26
Layout -4 brainstorming with customer technical staff

MF
C
Nitrogen heater
NH
CIP
V-48 P-131
P-127
Process N 2
CIP
This vanne can be taked
off after config
modification
P-125
TE
V-45
P-132
E-59
P-121
P-122
Chemicals
E-60
PE
Deaerator
P-120
CE
V-47
AIR
V-2
P-123
V-8
E-58
V-3
F-2
F-3
V-6
Exhaust gas
V-5
V-4
V-14
V-12
V-9
Supplemental
Safetety filter
Manage CIP
when filter is
removed.
P-163
V-11
V-7
PI
LI
CIP
P-1
V-13
This vanne can be taked off
after config modification
V-10
P-10
P-6
P-9
P-8
P-3
P-4
P-2
Study Linear gas
inlet if varant with
two outlet filters
is selected
Study sampling
Various
containers
volume with the
same head
P-5
P-7
SG
walter
Valutate using a stedim
sartorius addition port
This flange must be used
onto Muller drums and
other containers from
different volumes
walter
Valutate to perform back
flush via a second sinter
port instead of trough the
sparger.
PAT ? For in
process control
walter
Biosafeport sartorius
Miki
A
B
supply 1 KG fine lactose to allow Jean’s engineering of sampling unit
Send a layout of batch sequences
Due to the use of pneumatic lift, plan different
bottom distancers according to the drum height
Sampling
tube
Dismountable with
TC?
Only if the bottom
part will be of 1
welded pce, in this
case about 10
dedicated filter
funnels are nedeed
CIP Supply
CE
P-128
V-49
P-130
P-133
°C
FE
LE
P-124
F-1
V-1
Reserve process
analyse PAT
Water supply
walter
Automated micro powder dryer-P26
P-119
V-46
TE
CIP return

Final Head configuration layout (decisional to establish URS)
Gas Flow out
port
4-20mA
F-5.2
Supplemental services to be controled:
2 air actuators (con switch fine corsa)
F-5.1
1 air actauator big for cover lifting
Ch eck v
Eventualy 2 D C motors about 50w to
VC-5.1
150 watt maxon 1-Q -EC Amplifier
D ECS 50/5
Outlet sinter
Valves and filters
mounting proposal
V-5.3
4-20mA
V-5.2
V-9.2
CIP
port 4
Gas out
port 9
V-4.1
V-5.1
V-9.1
V-10.3
V-10.1
V-8.4
V-1.1
VC-9.1
Sampling
system
Outlet sinter
Mounting proposal
4-20mA
PI
Gas out Port 2-A
port 5
4-20mA ????’
PI
Port 2 Port 11
V-10.2
V-8.3
°C 4 -20m A
Sparger
port 1
V-1.3
V-8.2
V-9.0
10 valves ratti 3/4”
3 valves ratti 1-1/2”
F-9.1
°C 4-20mA
Vac trans
system
4-20mA
or PT
or K
1 o 2 KW
Heater 220 v
Temp switch
4-20mA
on/off
or OP
PFC-9.0
O P: digital RS-485; Modbus RT U
(Slave); Lab View-VI‘s available
Gas he at
4-20mA
or OP
NH-9.0
(for pressure and flow) O ption:
ProfiBus D P-V0, D P-V1
MFC
1 bal valve 1/4”
2 ball valve 3/4”
1 ball valve 1-1/2
Ball valves
Ghidin type 133
www.4gghidini.i
PFC
Test guaflon Membrane
MFC-9.0
V-8.1
Dryer load
port 8
Gas flow in port
Automated micro powder dryer-P26

Powder management under vacuum
Basic model used to develop process
Transfer
Sampler
Vaccum system
connected to sinter
Task-3 config
Task-5 config
1”
ball
valve
Sampling
with SPE
.
500 ml
Model integrated in glove boxes,
corrected after risk analysis FMEA
OMAL
DA-45
OMAL
DA-45
TOP
Vortex Powder management
View
Front

Liquid distillation model
N
2
flo
w
g
re
n
io
at
ul
CLEVER
1 to
20 L
RAW Product
1 to
20 L
DISTILLATE
RESIDUE
HELIX FLASH DISTILLATION
•Inert material construction
•No moving mechanical
parts
• temp range RT+10 to
300°C (for Glass Model)
•Pressure range +0.5 to
absolute vacuum
• Product/°C contact 5-10
seconds for water
equivalent viscosity
• Typical use, separation of
two fractions.
•Can be series mounted for
multi-fractions distillation.
• Used to distillate thermo
sensible products.

Melting solids distillation model
Pneumatic
actuated
powder
feeder
BE SMART
•Adding the powder feeder
and the in-line melting unit
to the liquid distillation
model; its possible to
distillate melting solids wit
the “Helix”
• A proved application is
purification of DTE.
IN-line
Powder
melting
Heater
Distillate
Residue
HELIX FLASH DISTILLATION
1L

Final packaging of pharmaceutical / different rooms
PASS BOX
RINSE STEP
1
V-102
P-247
P-233
V-86
E-82
CIP VENTURI BASED
Water supply
P-283
E-91
I-64
P-288
Deaerator
P-285
P-272
3
I-50
I-54
I-66
P-234
CIP Supply
P-260
5
I-51
I-51
V-104
AIR
The separator tank (3) is filled
trough one of the two separator
tank waffer filling valves(1). The
supply pump (2) draw the water
from the tank (3) and deliver the
solution to the process trough the
discharge control valve (4) at the
programmed flow rate. At the
same time, solution is pumped
trough the venturi eductor (5) and
back into the separator tank (3)
inlet, thereby ceating a vacuum at
the CIP return connection. The
high turbulence created within the
circuit prevents settling of any
solid and provides self cleaning of
the system. The rinse step is
followed ba drain step. Tipically, a
serie of 3-4 rinse/drain steps are
utilised for the final rinse proven
by low conductivity at the Cip
return connection.
Chemicals

4
P-266
P-228
P-276
V-96
P-250
2
E-80
V-103
P-286
P-232
V-92
P-286
I-64
CIP return

DRAIN STEP
Water supply
V-94 P-271
P-246
P-239
V-100
E-88
E-84
I-48
P-281
Deaerator
P-251
P-255
3
I-59
I-65
I-61
P-253
CIP Supply
P-274
5
I-55
I-55
V-84
4
AIR
Chemicals
The discharge control valve (4)
is closed and solution from the
separator tank (3) is pumped
trough the venturi eductor (5)
and back into the separator
tank (3) inlet, thereby ceeating
a vacuum at the CIP return
connection. Returning solution
create a high-level condition in
the separator tank (3) causing
the drain control valve (6) to
bleed solution to drain at the
set flow rate until the process
and the separator tank (3) are
empty.
P-263
P-235
E-90
V-99
P-267
CIP VENTURI BASED
P-236
P-290
V-85
P-261
6
V-88
P-267
I-48
CIP return

WASH STEP
The separator tank (3) Is filled
trough one of the the two separator
tank water fill valve (1). The supply
pump (2) draws the water from the
separator tank (3) and deliver the
solution trough the process trough
the discharge control valve (4) t the
programmed flow rate. At the same
time, solution is pumped trough the
venturi eductor (5) and back into the
separator tank (3) inlet, thereby
creating a vacuum at the CIP return
connection. he high turbulence
created within the circuit prevents
settling of any solid and provides self
cleaning of the system. CIP solution
temperatures are elevated using the
a heater (7) in the recirculation loop.
Chemical solutions (8) are injected
into the highly turbulent separator
tank (3) and controlled trough
conductivity..
CIP VENTURI BASED
30 LITER BIOREACTOR
Pneumatic
valves

Incorrect
rappresentation
240
25 L
Pneumatic
valves
650
15 L
Vxxx
½ gas OD
21.3 x1.6
½ gas OD 21.3 x1.6
Bioreactor P&ID
7901 custom manufacturing, customer requirements for VMP

7901 custom manufacturing customer requirements for VMP
7901 PRODUCTION
PROCESS AND
Customer validation requirements
DOCUMENTS
VCF: 3
work order
Process
validation
CAMPAIGN
DOCS
external
contractor
cleaning
startup
PPSOP-5
Entry
INSTRUCTION
Equipment startup
validation
protocol
PPI1
cleaning
Production
process
records
CLEANING
Batch
record
End of
campaign
cleaning
Validation
report
End of campaign
cleaning report
batch record
PPI-1 startup
RM withdrawal
Box entry
box day check
box cleaning
CLEANING
VALIDATION
Batch review
campaign closure
Production batch
1 batch manufactured in 3 portions
MB
R
MBR-02-000-07901-09
Humid
(the 708 g
dried)
Humid
(the 708 g
dried)
Humid
(the 708 g
dried)
Ca 250 g (humid)
MB
R
End of
campaign
cleaning
Intermediate release
Ca-1690 g*
(Yield79.36%)
MBR-02-000-07901-05
MBR-02-000-07901-05
end of campaign cleaning
MB
R
MBR-02-000-07901-01
Commercial
Not for sale
CA 1370 g *
NCC, crusts
* indicative values only
EQUIPMENT
Steroids Dedicated reaction and filtration
unit
IQ
OQ
strartup
PPI-1 Production room Class: not
required
IQ
OQ
monitoring
Dried in
Filter
Release methods
General, compendial based
External, compendial based
Silver X ray
Appearance
A customer need to
manufacture a new API for
clinical trials Phase III.
In order to fix the Validation
requirements for this
process, graphical
representation was lay down
Product specifics
HPLC Purity
IR identification
HPLC DAD UV Identification
Residual solvents
External, product specific
Water
Particle size (laser)
Transfers and packaging
PPI-1 Production room Class: not
required
IQ
OQ monitoring
Notes: document version, reported weight are only indicative and subject to change according to process evolution
Not required
Required
7901 VMP.vsd
Project management flows in API processing

7901 graphical batch record test for presentation
Project management flows in API processing

7901 Graphical Equipment Configuration sheet
After Process batch record
was defined, a graphical
representation of required
equipment configuration
was lay down
Project management flows in API processing

7901 Graphical micronisation external supplier control form-1
CRYSTALLINE LOT
Lot: FP-07901/………...
Analytical sample
Main quantity
COA
RA
ORDER
MBR
Other
QTY in grams……………...
QTY in grams……………...
Related documents
Specification and reference
PVP
IPM
SOP
Other
SS-02-0000-07901-01
< 5 µm
d (0.90)
Certificate
Packing and labelling part
Assigned lot Nr
Container
Labels
Consigned
Received
Used
Returned
Check
……...
Lot: FP-0790101………...
Container: None
FP label
QC retained
sample
Lot: FP-0790101-…………...
Lot: NCC……………...
Labels:
……...
Container: ……..
Labels:
……...
Container: None
Rest of mill
NCC
tare
Labels:
……...
Labels:
……...
Container: None
Labels:
Crystalline API will be
Micronised by an approved
external supplier.
The form on left details the
Product shipment and
receiving protocol page 1
……...
Sign/check
Symbol
category
N/A
Brown HPDE
Material
Standard. volume
100 mL
Sicor
Supplied by
N/A
Brown HPDE
1000 mL
Sicor
N/A
N/A
Jet pharma
Drum
N/A
Jet pharma
Shipment and receipt of crystallyne
Carrier: ………………………………………..
Jet pharma consigned on: ……………………… AT: …………………………...
TR receipt NR: ………………………………….. Send on…………………By:…..………….
Micronisation and packaging
For milling and in-process control, add as documentation:
A
Copy of the micronisation report
B
Copy of particle size analysis of crystalline, in-process control, and final product
C
Copy of monitoring for microbiological and particles monitoring of the micronisation equipment and box.
D
Copy of the certificate of analysis of the milling fluid (Nitrogen)
E
Copy of the particle size determination SOP.
F
Schematic drawing of the microniser and related box.
G
Maximum 10 days after consignment of the micronised product, results of microbiological analysis
H
Completed sections of this batch record
G
Weighing table reporting each portion and related retained samples taken
Color code for sections to be completed by Manuf.
Function
Operator
Supervisor
Check
Date
Color code for sections to be completed by microniser
Function
Check
Date
Operator
Supervisor
Project management flows in API processing

7901 Graphical micronisation external supplier control form-2
Manuf receipt
Receipt on
Date ……….
Y/N: ……….
Check packaging page for containers and labels
Check: ……….
Check: ……….
Documentation as reported in Microniser part:
Copy of the micronisation report
Y/N: ……….
Check: ……….
Copy of particle size analysis of crystalline, in-process
control, and final product
Y/N: ……….
Check: ……….
Copy of monitoring for microbiological and particles
monitoring of the micronisation equipment and box.
Y/N: ……….
Check: ……….
Copy of the certificate of analysis of the milling fluid
(Nitrogen)
Y/N: ……….
Check: ……….
Copy of the particle size determination SOP.
Y/N: ……….
Check: ……….
Schematic drawing of the microniser and related box.
Y/N: ……….
Check: ……….
Maximum 10 days after consignment of the micronised
product, results of microbiological analysis
Y/N: ……….
Check: ……….
Completed sections of this batch record
Y/N: ……….
Check: ……….
Weighing table reporting each portion and related retained
samples taken
Y/N: ……….
Check: ……….
Manuf warehouse operations
Lot
:………………
.. Total grams: …………..
Number of containers: ……….
Group all containers of product in specification and its retained
sample in a box and store the box with a quarantine label in
quarantine area
Number of containers: ………
Grams: ………………...
WH : ………….
Log the product and complete withdrawing forms
Lot
:………………
Y/N: ……….
QC: …………...
Crystalline API will be
Micronised by an approved
external supplier.
The form on left details the
Product micronisation and
back receiving protocol page 2
.. Total grams: …………..
Number of containers: ……….
Store and login crust container in NCC
Y/N: ……….
WH: ……….
Manuf batch record pre-approval and notes
Notes: ……………………………………………………………………………………………………………
……………………………………………………………………………………………………………………….…………………………………………
…………………………………………………………………………………………………………………………………………………………………
QC pre-approval
OK on: …………..
QC: ……….
M-Bial results on batch will be send later
OK on: …………..
QA: ……….
Project management flows in API processing

7901 Graphical example, yield sheet
7901 xxxxX-2001
7901 xxxxX-2005
Campaign C-18
488 g (68.9)
540g (76.3)
FP-01/019
FP-01/019
R
DCU out
473.4
7901-09
Starting 7879
3 x 265= 795 g
xxxxxxnide
1500 g
0790109-00105
Used in humid form
2456.9 g
R
534.2
1690.1g
(79.36%)
0790105-00105
7901-05
926g (65.4)
FP-01/021
1682 g
905
1575.5g (93.7%)
7901-05
reprocessing
0790105-00205
1567.5 g
Mic Mac
682g (75.3 %)
FP-01/022?
Micro loose
al included
24.7%
103g (11.7%)
NCC crusts
Jet pharma
1372.0 g (85.5%)
37.0 g (2.3%)
0790101-00105
NCC crusts
7901-01
Micro loose
al included
14.5%
Process and Yield
comparison between
external suppliers
performing
micronisation
Miller loose
5.3%
yield as micronised
calculated on xxxxxnide
as starting: 91.5%
yield as micronised
calculated on Cp-7879 as
starting 173%:
Lotto
Mulino
Fluido Processo
P.Entrata P.Macinazione
Feed rate G.PartenzaN.Micro
FP-01/022 Mc.50 GB ARIA
8.00
8.00
0.130
905.0 2 volte
G micro Yield
682 75.35912
Project management flows in API processing