welcome to my graphical knowledge summary
DESCRIPTION
Welcome to my graphical Knowledge summary. Dussex Jean-Charles Via pizzamiglio,9 CH-6833 Vacallo [email protected] . FROM IDEA TO APPLICATION. Summary of system actors. TQMS-1. Presentation in Work breakdown structure style. TQMS-1. - PowerPoint PPT PresentationTRANSCRIPT
Welcome to my graphical Knowledge summary
Dussex Jean-Charles Via pizzamiglio,9 CH-6833 Vacallo [email protected]
FROM IDEA TO APPLICATION
TQMS-1
Summary of system actors
TQMS-1
Presentation in Work breakdown structure style
TQMS-2
Procedure deviation process according to deviation criticality
PROCEDURE DEVIATION
Approved PDR
Impact
majorLOT
INVESTIGATION
BATCH RELEA
SEMinor
Other batches to be manufactured ?
Yes
Approved PDR
Attached to the MBR as manufacturing instruction
FOR PLANNED DEVIATION
CHR
Open a Change report or fill in already open CHR
Apply change
LIRdecision
IncludesPDR
references
7 56
121110
8 4
21
9 3
immediately
7 56
121110
8 4
21
9 3
Before batch releaseIn parallel
REJECTED
Examples of Processes Scenario
CHR
BATCH RELEAS
E
IncludesLIRreference
sCustomer
Reprocess
7 56
121110
8 4
21
9 3
ASAP
BATCH RELEA
SE
IncludesPDR
references
LIR
Report deviationAssess impact
on product quality
Wait until a reasonable number of minor changes are to be applied,
and or validation process occursNormally during annual review
process
Batch destination
and changes to be applied
are taken in LIR decision
TQMS-3
Process parameter design space
Design space
Rpoted in Batch card
Used for proces optimisation
Ensure product Quality
Recommended Process parameters
Working parameter range
MBR
CRIT
ICAL
PRO
CESS
PAR
AMET
ER
CRIT
ICAL
PRO
CESS
PAR
AMET
ER
Reported in DMF
Instruments calibration range
Process limit for product quality
Critical Critical
Development report
May be updated
Operational process
parameter
May be updated
Operational process
parameter
Significant process parameter
Significant process parameter
TQMS-4
Validation workflow
Development studies
Process and Product characterisation
Manufacturing equipment capability
Prior manufacturing Experience
Risk AssesmentDefine critical
product & Proces attributes
Define Critical and Key Operational
Paameters and their Ranges
Scientific Judgement
Process & ProductCharacterisation
Report(s)Process Development Report(s) Updated Process
Understanding
ProcessValidation
Master Plan
ProcessPotocols
Production Records
ManufactureConformance
Lots
ProcessValidation
Reports
OngoingProcess
Monitoring
PROCESS DESIGN PHASE
Process qualification
phase
Process development
Commercialisationphase
Link to QualificationActivities:
Equipmnt, Utilities,Facilities, raw Materials
Risk analysis
Filter dryer Failure Mode Effect Analysis-01
FMEA Number --->
Product / Service Identifier --->
Telephone #:
Process being analyzed --->
FMEA Revision Date------>
Core Team --->
Process activity Potential Failure Mode
Potential Effect(s) of Failure
Sev
Type
Potential Cause(s) / Mechanism(s) of
Failure
Fishbone Cause
Category
Occ
Current Process Controls - Prevention
Current Process Controls - Detection
Det
RPN
Recommended Actions
Responsibility & Target
Completion DateActions Taken
Sev
Occ
Det
RPN
powder suction do not suck block process 5 I Transfer line stopped method1
Backflush vibrate , repair or replace
None10 50
do not suck block process 5 I Sampler valve blocked
machine1
Backflush vibrate , repair or replace
none10 50
do not suck block process 5 I vacuum valve blocked
man1
Backflush vibrate , repair or replace
none10 50
do not suck block process5
I Vacumm pump out Fishbone Cause
Category3
Repair or replace pump
none10 150
do not suck block process5
I lump formed3
DE-lumper system+Back flush
No powder in sampler 10 150
do not suck block process 5 I Hole formed Hole at suction point
?3
main container stirred or vibrated
No powder in sampler 10 150
Hardware failures Pneumatic actuators leaks
Cross contamination risk for product and containement 10
Mechanical or pneumatical sealing
machine
1
located in the glove box
no powder sampled
10 100
Seal between valve and actuator leaks
Cross contamination risk for product and containement 10
Mechanical or pneumatical sealing
machine
1
located in the glove box
?
10 100
Eric Cartman (Operations Manager), Kenny (South Park Store Manager), Marge Simpson (Springfield Store Manager), Stan Marsh (pizza creation associate), Kyle Brovlowski (BPI associate), Mr. Garrison (purchasing and inventory manager), Mr. Hand (pizza creation associate), Chef (BPI Manager)
Filter dryer FMEA-01
as required
Email address:
DJCPrepared by --->
Original Date ---> 07.01.2011Powder transfer system Other relevant information ---> visio cause effect diagram
Filter dryer+powder tranfer system
Level of DetailFMEA Type
Design or Process Responsibility -------------> DJC
System Process Component / PartDesign FMEA Process FMEA Process Step
Risk analysis
Cause Effect Diagram: sampling sys. no powder transferred
Some concepts
Process transfer and Equipment qualification
Process transferEquipment Qual.
Personnel flow, room pressure and class
Example of Room layouts and symbols
C D N
Class
Personnel inTrafic zone
+++
++
+
---
--
-
Pressure
-20 pA
-10/-15 pA
--25/-30 pA
+25 pA
+25/-30 pA
+10/-15 pA
Some room characteristic
symbols
Personnel clothing steps
Personnel flow
Factory entrance
Factory personnel entry from 008 to corridor 022
IN Steps Symbol Local Description Status 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
Qui si segrega le vie per personale ufficio, laboratorio, magazzino etc..
il personale di produzione segue la via step 3 e succsessivi
PRODUCTION STAFF
Non-Production
Staff
Personnel flow
Class D surrounding area3
Corridor 012 & 013
Mette le calze di nylon (usa e geta) e le scarpe di produzione
4
012 & 013 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 1AUTHORISEDPERSONNEL
ONLY
5
018 Desinfetta le mani, passa sas 016 ed accede ai corridoi di produzione 022 028, 029 , lift, 129, 128,121
6 Personnel is now able to travel in Class D corridors
and access to Sas entry of the manufacturing boxes
Personnel flow
Specific workplace in qualified roomPersonnel access to BOX 023
IN Steps Symbol Local Description Status 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 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.
Factory planning-P26
Water system 090320
Pre-URS discussion for project definition
Chromatography system pre-layout
Pre-URS discussion for project definition
Chromatography system Project pre-layout phase 1
P and ID symbols 110303
Drawing symbols (CAD)
Filter dryer flow inversion static drying
Development and test of new drying concept/componentsFILTRATE VACUUM
SLURRYNITROGEN
1
<
NITROGEN
OUTLET VACUUM
°c2
OPEN VALVE
NITROGEN
OUTLET VACUUM
3
Load slurry
OPEN VALVE
NITROGEN
Transfer system
Final container
4
Dry
Move cake
Discard
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
Well Done.
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.
Filter dryer flow inversion drying tray model
Filter dryer-NEW study of critical contamination points
Filter dryer flow inversion static drying container
Filter dryer-NEW study of critical contamination points
E-2
P-18FilterWash
Vacuum oven
Filter and wash Transfer in drying container, Weigh Close ovenSample
Open and close oven
Vacuum ovenVacuum oven
Dry
Vacuum oven
FinishDrying
Vacuum oven
Remove from Oven, weigh and take sample
Transfer to final container
Close and clean final container
Product data label
Apply label, weigh….
Exit of the contaminated
area
Apply vacuum
Open valve
Product suction
Small pressure/equilibrate level
Close the valve
Stop or contain pipe end
P-24Appply vacuum Break vacuum
Open valve
Suction sampling
Apply vacuum
Close valve
Stop or contain pipe end
Continue drying/sampling
up to OK
Break vacuum
P-33
Conect final container
Conect final container
P-45
P-44
P-51
P-50
Product contained in dirty enclosureProduct contained in dirty enclosure
Product in contact with area areaProduct in clean enclosure
External enclosure not contaminated Minor risk of contaminationExternal enclosure contaminated Risk of contamination
AREA contaminated Risk of contaminationExternal enclosure not contaminated No contamination risk
Filter dryer flow inversion ancillary equipments
Schematic flow of drying operations
Further samplings, repeat the 5 above steps
At mounted container
Mount a new container
Loose a little bit sampling container
Sampling quantity OK
Sampling 1
Sampling Operation V1 V2 SAVV-1
V-2
SAV m
Sav, 2, 1
2,1, sav
Sequence
Disconnect the flushing connector
Disconnect V-1
Close V-1
Stop the lateral TC
Disconect the lateral TC onto the sampling tee
At decontamination OK
Fluch decontamination medium
At mounted flushing connector
The flushing connector
Decontamination / cleaningOperation V1 V2 SAV
m
Sav, 2, 1
2,1, sav
Sequence
Alternatively, depends of further planned operations, disconnect at the point wher flexible fit the SAV
Brouh the tee as is into a glove box in order to dismount it and decontaminate the superior part included the contaminated fi lter.
V-1
V-2
SAV
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 modules with sampling
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 DN150 based
Filter glass DN-150 with heating
FP-1
FP-2
FP-3
FP-4
FP-5
FP-2
FP-6
FP-7
ST-1
ST-2
V-1
V-2
Layout of filter dryer with in line heater unit.Integrated mass flow controller and flash heating assembly
Containment glove box-P13
Glass reactor units, skid mounted into glove boxes P-13
1499
85
6
1398 799
744
670
R4A R3AT6A R4BT6BR6B Gs1
PLAN
FACE
BOX-1BOX-2BOX-3
Containment glove box-P13
Reactor Skid and special vacuum line
R4A R3AT6A
BOX 3 Unit
IF2A
R4BT6BR6B
BOX 2 Unit
Gs1
Flex toG1/2” male
Containment for filtering/drying
Filter 10 inches in glove box, pre-layout
OPTIONAL STIRRED FILTER
STATIC FILTER
TOP VIEW
Containment area for biotech
Clostridium high contamination risk lab layout ed2
Surrounding area 1 P: +++
Surrounding area 2P: --
“Nursery”AreaP: ---
“Kitchen”P: +
Wall autocalve
Reactors areaP: ---
Product separation area?P: ---
Material and productsdecontamination area
P: ---
QC areaP: ---
RM non cotaminated in
P:++
Personnal Changing
room 1 in and out
P:++
Personal in changing room 2
P: +
Personal out decontaminati
ionP: ---
Personal out decontaminati
ion-2P: --
Product out decontaminati
ion 2P: +
Product out out 3P: ++
Intermediate Sas material and equipment
P: -Wall SAs
+++
++
+
---
--
-
Pressure
-20 pA
-10/-15 pA
--25/-30 pA
+25 pA
+25/-30 pA
+10/-15 pA
++++ ++
+---
-
--
++
--------- ------
+++
Automated micro powder dryer-P26
Layout -1 with one outlet candle filter
PL-1 Pneumatic lift PlC safety durig opening
P-1P-2P-3P-4P-5P-6P-7
SpargerPressure sensor
Reserve/Cip out?CIP port inGas out+ Pt100
P-6P-7
Internal TK 1-1/2”TC 1-1/2 or NW 32TC 1-1/2 or NW 32TC 1-1/2 or NW 32TC 1-1/2 or NW 32
Port Assigned to ConnectorMass flow + Heater+PLC
OVP+PLCSensor+PLC
CIPTC 1-1/2 or NW 34 or TKEventual sight glass+ lightEventual sampling port
Ancilliary
P-8 Product filling PlC safety durig opening
P-1
P-2
P-3
P-4
P-5
P-6
P-7
P-8
LISG
PI
.
°C
V-6 V4
V-1
Exhaust gas
CIP
Process N
2
V-7
V5
V-2
V-3
F-1
V-8
P-8P-7P-6P-5P-4P-3P-2P-1Item
Product fillingSampling or resserve portSigght glass and related lightGas out+PT100CIP in to sprayballReserve/CIP outPressure sensorSpargerAssigned to
PLC to mange signal ?Light to PLCPT-100 connected to PLC
Pressure sensor PLC connected to PLCCustom made with sinterDescription
P-28
P-28
CIP
V-8V-7V-6V5V4V-3V-2V-1
Valves
Process gas inGas outGas outProcess gas inProcess gas inCip INCip iNCip INAssigned to
Check valvePneumatic actuated membrane valvePneumatic actuated membrane valvePneumatic actuated membrane valvePneumatic actuated membrane valvePneumatic actuated membrane valvePneumatic actuated membrane valvePneumatic actuated membrane valveDescription
V-9
V-9 Gas out Check valve
?xx??X
FlowPLC
xxxxxxxx
PLC
x
MFC
Nitrogen heaterNH
P-36
PL-1CIP
MFCNHItem
Pneumatic lift?Mass flow controllerNitrogen heaterAssigned to Description
?xx
PLC
CIPP-72
Automated micro powder dryer-P26
Layout -4 brainstorming with customer technical staff
P-1
P-2
P-3
P-4
P-5
P-6
P-7
P-8
LISG
PI
F-2°C
V-6 V-4
V-1
Exhaust gas
CIP
Process N
2
V-7
V-5
V-2
V-3
F-1
CIP
V-9
V-8
MFC Nitrogen heater
NH
CIP
Dismountable with TC?Only if the bottom part will be of 1 welded pce, in this case about 10 dedicated filter funnels are nedeed
F-3
Supplemental Safetety filter
Valutate to perform back flush via a second sinter port instead of trough the sparger.
Study sampling
Various containers volume with the same head
Valutate using a stedim sartorius addition port
PAT ? For in process control
MikiA supply 1 KG fine lactose to allow Jean’s engineering of sampling unitB Send a layout of batch sequences
Study Linear gas inlet if varant with two outlet filters is selected
Manage CIP when filter is removed.
This flange must be used onto Muller drums and other containers from different volumes
Due to the use of pneumatic lift, plan different bottom distancers according to the drum height
Biosafeport sartorius
walter
walter
walter
walter
V-14
P-9
P-1
0V-10
V-11
P-163
V-12
V-13
Samplingtube
This vanne can be taked off after config modification
This vanne can be taked off after config modification
Reserve process analyse PAT E-58
E-60
P-124
AIR
Deaerator
P-123
V-47CE
TE
P-128 CIP return
P-122
E-59TE
P-121
V-48
P-125
Water supplyP-131
FEPE
P-120LE
CE
V-45 P-132
P-127
Che
mic
als
CIP Supply
V-49
V-46
P-119
P-133
P-130
Automated micro powder dryer-P26
Final Head configuration layout (decisional to establish URS)
Check v
Gas
he
atM
FC
Sampling system
Dryer loadport 8
Spargerport 1
CIPport 4
Gas outport 5Gas out
port 9
Gas Flow outport
V-9.0V-1.3
F-9.1
VC-9.1
PFC-9.0
NH-9.0
MFC-9.0
V-10.3
V-10.1
V-10.2
V-1.1
V-5.1V-9.1
V-5.2V-9.2
V-4.1
V-5.3
VC-5.1
F-5.1
F-5.2
PFC
V-8.1
V-8.2
V-8.3
V-8.4
Vac transsystem
10 valves ratti 3/4”3 valves ratti 1-1/2”
4-20mAor PT or K
4-20mA
4-20mA
4-20mAor OP
4-20mAPI
Port 2
????’
Port 11
Test guaflon Membrane
1 bal valve 1/4”2 ball valve 3/4”1 ball valve 1-1/2Ball valvesGhidin type 133www.4gghidini.i
4-20mAPI
Port 2-A
1 o 2 KWHeater 220 v
4-20mA°C
Temp switch on/off
4-20mA°C
OP: digital RS-485; Modbus RTU (Slave); Lab View-VI‘s available(for pressure and flow) Option: ProfiBus DP-V0, DP-V1
4-20mAor OP
Supplemental services to be controled:2 air actuators (con switch fine corsa)1 air actauator big for cover liftingEventualy 2 DC motors about 50w to 150 watt maxon 1-Q-EC Amplifier DECS 50/5
Gas flow in port
Outlet sinterMounting proposal
Outlet sinterValves and filters mounting proposal
Vortex Powder management
Powder management under vacuum
Vaccum system connected to sinter
Task-3 config Task-5 config
Transfer
.
Sampler
500 ml
1” ballvalveSampling
with SPE
OMALDA-45
OMALDA-45
TOP View Front
Model integrated in glove boxes, corrected after risk analysis FMEA
Basic model used to develop process
HELIX FLASH DISTILLATION
Liquid distillation modelN2 flow regulation
1 to20 L
1 to20 L
DISTILLATE
RESIDUE
RAW Product
•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.
CLEVER
HELIX FLASH DISTILLATION
Melting solids distillation model
1 LPneumatic actuated powder feeder
IN-line Powder melting Heater
Residue
Distillate
•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.
BE SMART
PASS BOX
Final packaging of pharmaceutical / different rooms
CIP VENTURI BASED
RINSE STEP
E-80
E-82
P-260
AIR
Deaerator
P-228
V-104I-51
I-64
P-276 CIP return
P-272
E-91I-64
P-285
V-102
P-233
Water supplyP-283
I-54I-50
P-234I-66
I-51
V-86P-288
P-247
Che
mic
als CIP Supply
V-96
V-92
P-250
P-286
P-266
V-103
P-232
P-286
3
1
4
5
2
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.
CIP VENTURI BASED
DRAIN STEP
E-90
E-88
P-274
AIR
Deaerator
P-235
V-84I-55
I-48
P-290 CIP return
P-255
E-84I-48
P-251
V-94
P-246
Water supplyP-271
I-65I-59
P-253I-61
I-55
V-100 P-281
P-239
Che
mic
als CIP Supply
V-85
V-88
P-261
P-267
P-263
V-99
P-236
P-267
3
45
6
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.
CIP VENTURI BASED
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..
Bioreactor P&ID
30 LITER BIOREACTOR
½ gas OD 21.3 x1.6
½ gas OD 21.3 x1.6
Pneumatic valves
Vxxx
Incorrect rappresentation
Pne
umat
ic
valv
es
25 L
15 L
650
240
Project management flows in API processing
7901 custom manufacturing, customer requirements for VMP
work order
MBR-02-000-07901-09
Production process records
Batch record
batch record
RM withdrawal
CLEANING
End of campaign cleaning
Batch review
End of campaign cleaning report
Process validation
validation protocol
Validation report
MBR-02-000-07901-05
MBR
MBR
Production batch
7901 PRODUCTION PROCESS AND DOCUMENTS
CLEANINGVALIDATION
INSTRUCTIONPPI-1 startup
box cleaning
startup PPSOP-5
Equipment startup
Box entry box day check
campaign closure
CAMPAIGN DOCS
external contractor cleaning
PPI1 cleaningEntry
EQUIPMENT
Release methods
HPLC PurityAppearance
IR identification
HPLC DAD UV Identification
General, compendial based Product specifics
Transfers and packaging
IQ OQ monitoring
VCF: 3Customer validation requirements
End of campaign cleaning
Ca 250 g (humid)
Ca-1690 g*(Yield79.36%)
PPI-1 Production room Class: not required
Residual solvents
Silver X ray
External, compendial based
External, product specificParticle size (laser)
MBR-02-000-07901-01
MBR
Water
CA 1370 g *
Humid (the 708 g
dried)
Humid (the 708 g
dried)
Humid (the 708 g
dried)
1 batch manufactured in 3 portions
NCC, crusts
Not for saleCommercial
* indicative values only
Steroids Dedicated reaction and filtration unit
PPI-1 Production room Class: not required
IQ OQ
IQ OQ monitoring
strartup
Dried in Filter
Intermediate release
Notes: document version, reported weight are only indicative and subject to change according to process evolution
MBR-02-000-07901-05end of campaign cleaning
7901 VMP.vsd
7901 custom manufacturing customer requirements for VMP
Not required Required
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
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
Lot: FP-0790101-…………...
Lot: FP-0790101-………...
Lot: NCC……………...
Consigned Received Used Returned Check
Container: None
Labels:
……...
Labels
FP label
QC retainedsample
NCC
tare
Container
Sign/check
Lot: FP-07901/………...
Related documents
CRYSTALLINE LOT
COARA
ORDERMBROther
Specification and referencePVP
SOPOther
IPM Certificate
Packing and labelling part
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 reportB Copy of particle size analysis of crystalline, in-process control, and final productC 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 analysisH Completed sections of this batch recordG Weighing table reporting each portion and related retained samples taken
Function Check DateOperator
Supervisor
d (0.90) < 5 µmSS-02-0000-07901-01
Function Check DateOperator
Supervisor
category N/A Material Brown HPDE Brown HPDE
Drum
Symbol
Standard. volume 100 mL 1000 mL N/A N/A Supplied by Sicor Sicor Jet pharma Jet pharma
Assigned lot Nr
N/A N/A
Container: ……..
Labels: ……...
……...
Container: None
Labels: ……...
Labels: ……...
Container: None
Labels:
……...
Analytical sample
QTY in grams……………...
Main quantity
QTY in grams……………...
Color code for sections to be completed by microniserColor code for sections to be completed by Manuf.
Rest of mill
Crystalline API will be Micronised by an approved external supplier.The form on left details theProduct shipment and receiving protocol page 1
Project management flows in API processing
7901 Graphical micronisation external supplier control form-2Manuf receipt
Receipt on
Check packaging page for containers and labels Check: ……….
Check: ……….
Y/N: ……….
Documentation as reported in Microniser part:
Y/N: ………. Check: ……….Copy of the micronisation report
Check: ……….
Copy of particle size analysis of crystalline, in-process control, and final product
M-Bial results on batch will be send later
Copy of monitoring for microbiological and particles monitoring of the micronisation equipment and box.
Y/N: ……….
Check: ……….
Check: ……….
Y/N: ……….
Y/N: ……….
WH: ……….
Copy of the certificate of analysis of the milling fluid (Nitrogen)
Date ……….
Manuf warehouse operations
Group all containers of product in specification and its retainedsample in a box and store the box with a quarantine label in
quarantine area
Log the product and complete withdrawing formsY/N: ……….
WH : ………….
QC: …………...
QA: ……….
Store and login crust container in NCCY/N: ……….
Number of containers: ……….
Number of containers: ………
Grams: ………………...
Number of containers: ……….
Lot :……………… .. Total grams: …………..
Lot :……………… .. Total grams: …………..
Manuf batch record pre-approval and notes
OK on: …………..
QC pre-approval OK on: ………….. QC: ……….
Notes: ……………………………………………………………………………………………………………
……………………………………………………………………………………………………………………….…………………………………………
…………………………………………………………………………………………………………………………………………………………………
Check: ……….Y/N: ……….Copy of the particle size determination SOP.
Check: ……….Y/N: ……….Schematic drawing of the microniser and related box.
Check: ……….Y/N: ……….Maximum 10 days after consignment of the micronised product, results of microbiological analysis
Check: ……….Y/N: ……….Completed sections of this batch record
Check: ……….Y/N: ……….Weighing table reporting each portion and related retained samples taken
Crystalline API will be Micronised by an approved external supplier.The form on left details theProduct micronisation and back receiving protocol page 2
Project management flows in API processing
7901 Graphical example, yield sheet
FP-01/019
488 g (68.9)
R
FP-01/019
540g (76.3)
RDCU out
FP-01/021
534.2473.4
926g (65.4)
905
Micro looseal included
24.7%
0790109-001057901-09
7901-05
0790101-001057901-01
7901 xxxxX-2001 7901 xxxxX-2005
Used in humid form2456.9 g
7901-05 reprocessing
0790105-00205
1575.5g (93.7%)
0790105-00105
1690.1g (79.36%)
1682 g
1567.5 g
Jet pharmaMic Mac
NCC crusts103g (11.7%)
FP-01/022?682g (75.3 %)
1372.0 g (85.5%)
NCC crusts
37.0 g (2.3%)
Miller loose5.3%
Lotto Mulino Fluido ProcessoP.Entrata P.MacinazioneFeed rate G.PartenzaN.Micro G micro YieldFP-01/022 Mc.50 GB ARIA 8.00 8.00 0.130 905.0 2 volte 682 75.35912
Micro looseal included
14.5%
Campaign C-18 Starting 78793 x 265= 795 g
xxxxxxnide1500 g
yield as micronised calculated on xxxxxnide
as starting: 91.5%
yield as micronised calculated on Cp-7879 as
starting 173%:
Process and Yield comparison between external suppliers performing micronisation