QUS 1: - WHY NEGATIVITY IS REQUIRED IN COATING
PAN.
QUS
2: - COTTON SATIN % OR
POLYPROPYLINE %.
ANS DD INDUSTRIAL FABRICS (INDORE
DEASOZA)
SPECIFICATION OF POLY PROPYLINE (100% POLY
PROPYLINE) GREY CLOTH IS FOLLOWINGS:
TYPE OF WEAVE: -
TWILL
G.S.M (GRAM SQUARE PER
METER) OR FABIRC WEIGHT 5% OF 300.
PARTICLE RETENTION IN
MICRON 15 TO 20 MICRON (MESH SIZE 300)
AIR PERMIABILITY IN CU.
FT/ S.Q/ SEC: 0.83
OPERATING TEMPERATURE :-
95 TO 120 DEGREE CENTIGRADE.
BREKING STRENGTH (KG)
WARP: - 66
RESISTENCE TO ALKALIES
AND ACID: - EXCELLENT
RESISTENCE TO ABRASION,
OXIDIZING, DRY HEAT AND MOSITURE: - FAIR
SPECIFICATION OF PC SATIN WEAVE GREY (100%
COTTON GRAY CLOTH) CLOTH IS FOLLOWINGS:
TYPE OF WEAVE: -
SATIN WEAVE
G.S.M (GRAM SQUARE PER
METER) OR FABIRC WEIGHT 5% OF 460
PARTICLE RETENTION IN
MICRON 5 TO 9 MICRON (MESH SIZE 400)
AIR PERMIABILITY IN CU.
FT/ S.Q/ SEC: 9.9
OPERATING TEMPERATURE :-
160 TO 220 DEGREE CENTIGRADE.
BREKING STRENGTH (KG)
WARP: - 38
RESISTENCE TO ALKALIES
AND ACID: - FAIR OR POOR
RESISTENCE TO ABRASION,
OXIDIZING, DRY HEAT AND MOSITURE: - GOOD
Indrakshi enterprises,
anoop nager indore.
DD industrial fabrics,
D,souza House G-103 MIG colony Indore.
QUS 3: - FBD
BAG MESH SIZE OR HOLLENDER SIEVE SIZE OR DUTCH MESH.
ANS PHARMA
SPARE (TRUPATI K BHOSLE OR SANJAY GHANDI) SUPPLY THE FBD HOLLENDER SIEVE OF 125
MICON OR 110 MESH OF US STANDARD
MOC :- SS316
QUS 4: - SIEVE
LIFE CHECKING
QUS 6: - SS CHECKING TEST (MOLYBLEDEM TEST)
QUS 7: - RAPTURED DISC PRESSURE AND IN WHICH
CASE FBD CAN EXPLORE.
The pressure of rapture disk is min 1.75,’; max. 2.89 kg/cm2 It got rapture
when pressure increased due to static charge.
QUS 8: - BAFFLE TYPE AND SIZE OF COATING MACHINE
(TUBULER, RABBIT, FISH TYPE)
QUS 9: - RA FACTOR OR ROUGHNESS FACTOR OR GIRT
SIZE.
QUS10: - PUNCH DETERMINATION FOR NEW PRODUCT.
MOC OF PUNCH
IS OHNS& DIES HCHC ( OIL HARDEN NON SHRINKAGE)
TYPE
OVERALL LENGTH BARREL DIA. DIE O.D./hight Max .size of tab. May comp.
BB 133.60,+-
0.08mm(TSM)/133.36mm(ERO)19.00mm 24.0mm/22.22 mm 13mm(round),13
mm(shape)
B 133.60/133.36mm 19.00mm(0 to -.02mm) 30.16 mm/22.22 mm 16mm(R),15mm(S)
D 133.60/133.36mm 25.35 mm(0 to -.02mm) 38.10 mm/23.82 mm 25mm(R),24mm(S)
Head angle 36
deg/30 deg.
Head thickness 10.31mm/9.09mm
Hight of dies
contain of moc
carbon,chromium,cobalt,vanadium,silicon,Tungusten,magnesium
punch checking 100 mio tabs from one set . and rejection 10 mio tabs from one set ( 1 LP,1 UP, 1 Dies)
Following test r perform during punch
checking
1) go
no go test 2) cup depth= overall length – working length 3)tip concentricity 4)
tip size 5) barrel size
6) impression 7) dies height
,go nogo test for dies
Tolerance limit :
1)
Standard overallength = 133.60mm+- 0.08mm
2)
Working length = +- 0.05mm
3)
For cup depth=( Standard as per drawing ) +-
0.08mm, for embossed/break line +0.08mm to - 0.14 mm
4)
Tip concentricity +-0.03mm
5)
Punch barrel thickness :
6)
B type
U/P punches 19.00mm( +0.00 to -.02mm)
B
type L/P punches 18.95mm( +0.00 to -.02mm)
B type U/P & L/P punches19.00mm( +0.00 to -.02mm) Sejong
D type U/P punches 25.35mm( +0.00 to -.02mm)
D
type L/P punches 25.31mm( +0.00 to -.02mm)
D type U/P & L/P punches25.35
mm( +0.00 to -.02mm) Sejong
Key
angle for sjong is 15 degree and for cad press 45 degree
QUS11: - FBD BAG DETERMINATION FOR PRODUCT.(1
center,6,11 finger)
QUS12:- ODD PUNCH IN DOUBLE ROTATORY MACHINE
QUS13: - SIEVE TESTING AND CERTIFICATES (SANJAY
GANDHI PHARMA SPARES)
Two companies supplied the sieve and screen
1)
Pharma Spares (Snehal Gawde & sanjay Gandhi) ) 2) shree ram enterprise Indore or Man mach
industries Mumbai ( Shree Ram takes the
sieve and screen from Man mach.
MOC
and LEAD free certificate ( pb ,r used during welding of mesh ,but it is toxic
so that it should be from pb )
Certificate of nominal
apertures size.
This is to certify that the
sieve supplied is LEAD free and SS316 quality sieve.
Sieve is supplied as per ISO 9044 standards.
Mesh Count is 10# and nominal aperture the mesh
is 2057 microns.
Moulding elastomer used in sieve is pure
silicone (Polysiloxane)
USP-28 Toxicology test compliance
(Pharma Spare)
Elastomer
(Silicone) passes the systemic injection test. (test done as per USP 28 Page No
2269)
Pharma spares also provide the certificate
for complience taken from LABS LABS
In
this certificate he mentioned the standard used for sieve size checking (ISO
9044:1999- Industrial woven wire cloth technical requirement & testing),
technical committee ISO/TC24 prepares standard.
Test
report is as follows:
The
sieve is calibrated to the international unit of length by microscopy and image
analysis traceable to both the National Physical laboratory and IDDC.
Type
of Woven :- Plain woven
Instrument
for calibration:- Computerized Digital Microscope.
Calibration
Procedure:- The measurement of the aperture width is made in a number of field
evenly spread over the whole area of the sieve , and so chosen that no two
field area crossed by the same wire.
Number
of Aperture measured: - 30
QUS14: - FLEXIBLE CONNECTION CERTIFICATE (PHOENIX)
ANS MAKE : PHOENIX POLYNERS (A.D
KULKARNI) OFFICE : 16, GANGA MAHAL APTS. SR. NO. 36/2/01, PLOT NO. 108109,
KARVENAGER PUNE
020-5469542,
5434053
MOC:
60% CENTRIFUGED NATURAL RUBBER LATEX, ALONG WITH CURING AGENTS LIKE ZNO,
SULPHER LESS CURING SYSTEM, ANTIOXIDENTS, STABILIZER, ADDITION OF THESE CURING
AGENT NOT EXCEED 1.5 PHR.
QUS15: - SAP VERSION (R3 module, 4.7 version)
QUS16: - PLC VALIDATION PARTY ( KVI Ahmadabad)
QUS17: - FOOD GRANDE GASKETS MATERIAL (FOOD GRADE
RUBBER CLASSIFICATION)
QUS18: - PUNCH DETERMINATION FOR PREPICKED
PUNCHES.
QUS19: - INFLATABLE GASKETS OF ANCHOR
ANS SILICONE, HARDNESS IS SHORE A 60 (LIMIT 55 5 SHORE) AND SPECIFIC
GRAVITY IS 1.1.
QUS20: - PUNCH HARDNESS ( Rockwell)
QUS21: - AHU DIAGRAM( 10,3,0.30miccron)
QUS22: - IN BALANCE
e (Verification value)
d (resolution or least count or readability)
QUS23: - DIFFERENCE BETWEEN VERIFICATION AND CALIBRATION.
QUS24: - DWEEL TIME OR CONTACT TIME.
DWELL
TIME: - THE LENGTH OF TIME THE HEAD FLAT OF PUNCH IS IN CONTACT WITH THE
MAIN
COMPRESSION
ROLLER.
QUS25 CERTIFICATE
OF POLYTHENE BAGS.
(1)
R.S MOULD PLAST INDIA PVT. LTD.
OFFICE:
CHETAK CENTRE RNT MARG INDORE.
PHONE
NO. : 0731-4070286
(2)
Anant Packaging Industries, Dewas
(3)
Novex Poly films pvt. Ltd. (Mumbai) 022-23443921
This is to certify that the
material used to make polythene bag is food grade material LDPE, purchases from
Relience Ind. LTD.
Indothene
(Low density Polyphone): - Indothene is a film grade low-density polyethylene
produced by high pressure tubular process adopting , This grade meets the
requirements of Indian Standard IS-10146-1982.
The
grade also complies with USFDA regulation: 21 CFR parts 177.1520.
QUS25 SIZE OF
POLYTHENE BAGS.( 50*20 , 30*20)
QUS26 MOC
OF TURRET ( ss 316, cost steal)
QUS28 PLC SOFTWARE VALIDATIN AND VERSION
QUS29 SAP MODULES AND VERSION.
QUS30 MAXIMUM ALLOWABLE LOAD ON PUNCHES DURING COMPRESSION AS
PER THEIR SIZE.
QUS31 DOSATOR AND TEMPER CAPSULE FILLING MACHINE.
QUS32 MIS DATA, OEE, TEAM SHEET, YIELD REPORT, DLUR ETC.
QUS33 MOC SS316L AND SS316
QUS34 BALANCE e & d.
QUS35 LUBRICANTS USED FOR COMPRESSION MACHINE
ANS LIQIUED PARFIN (LESS VISCOUS WITH LESS LUBRICANTS
QUALITY)
SANTINEL (MORE VISCOUS WITH GOOD LUBRICANTS
QUALITY)
SO FOR VERY STICKY POWDER IT IS SUGGESTED TO
USE SANTINEL OIL.
QUS36 BUA
following test r performed in BUA
1) apperance 2)% LOD 3) blend uniformity 4)R.S.D
5) Assay
ANS Comments and
suggestions regarding this draft document should be submitted within 60 days of
publication
in the Federal Register of the notice announcing the availability of the
draft
guidance.
Submit comments to Dockets Management Branch (HFA-305), Food and Drug
Administration,
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be
identified
with the docket number listed in the notice of availability that publishes in
the Federal
Register.
For
questions regarding this draft document contact Jon E. Clark, 301-594-5613 or
Mike Gavini,
301-827-9053.
BUA guidance is intended to assist
manufacturers of human drug products
in meeting the requirements of
21 CFR 211.110 for demonstrating the adequacy
of mixing to ensure uniformity of in process powder blendes and finished dosage
units.
This
guidance has been prepared by the Office of Pharmaceutical Science and the
Office of Compliance
in the Center for
Drug Evaluation and Research (CDER) at the Food and Drug Administration in
cooperation with the Product Quality Research Institute (PQRI) (see footnote
3). This guidance document represents the Agency's Current thinking on
assessment of the uniformity of powder blends and finished dosage units in the
absence of new technology development or implementation.
The
Use of Stratified Sampling of Blend and Dosage Units to Demonstrate Adequacy of
Mix for
Powder
Blends.
Stratified
sampling is
the process of collecting a representative sample by selecting units
Deliberately
from various identified locations within a lot or batch, or from various phases
or
periods
of a process to obtain a sample dosage unit that specifically targets locations
throughout
the
compression/filling operation that have a higher risk of producing failing results
in the
finished
product uniformity of content.
The in-process dosage
unit is a capsule or tablet as it is formed in the manufacturing process before
it is coated or packaged.
Assessment of Powder
Mix Uniformity
We
recommend the assessment of powder mix uniformity using the following
procedures:
Conduct
blend analysis on batches by extensively sampling the mix in the blender and/or
intermediate
bulk containers (IBCs).
Identify
appropriate blending time and speed ranges, dead spots in blenders, and
locations
of
segregation in IBCs. Determine sampling errors.
Define
the effects of sample size (e.g., 1-10X dosage unit range) while developing a
technique
capable of measuring the true uniformity of the blend. Sample quantities larger
than
3X can be used with adequate scientific justification. Appropriate blend
sampling
techniques
and procedures should be developed for each product with consideration to
various
designs of blend powder sampling and the physical and chemical properties of
the
blend components.
Design
blend-sampling plans and evaluate them using appropriate statistical analyses.
Quantitatively
measure any variability that is present among the samples. Attribute the
sample
variability to either lack of uniformity of the blend or sampling error or
Significant
within-location
variance in the blend data can be an indication of one factor or a
combination of
factors such as inadequacy of blend mix, sampling error9 or agglomeration.
Significant
between-location variance in the blend data can indicate
that
the blending operation is inadequate.
EXHIBIT/VALIDATATION
BATCH POWDER MIX HOMOGENEITY
This
section describes sampling and testing the powder mix of exhibit and process
validation
batches
used to support implementing the stratified sampling method described in this
guidance.
We
recommend that during the manufacture of exhibit and process validation
batches, you assess
the
uniformity of the powder blend, the in-process dosage units, and the finished
product
independently.
We recommend you use the following steps to identify sampling locations and
acceptance
criteria prior to the manufacture of the exhibit and/or validation batches.
Carefully
identify at least 10 sampling locations in the blender to represent potential
areas
of
poor blending. For example, in tumbling blenders (such as V-blenders, double
cones,
or
drum mixers), samples should be selected from at least two depths along the
axis of
the
blender. For convective blenders (such as a ribbon blender), a special effort
should
be
made to implement uniform volumetric sampling to include the corners and
discharge
area
(at least 20 locations are recommended to adequately validate convective
blenders).
Collect
at least 3 replicate samples from each location. Samples should meet the
following
criteria:
Weight
correction is a mathematical correction to eliminate the effect of potentially
variable tablet weight on
measurement
of mix adequacy.
Contains
Nonbinding Recommendations
Assay one sample per location (number of
samples 209 les (n) ≥ 10)
(n
= 20 for ribbon blender).
RSD
(relative standard deviation) of all individual results ≤ 5.0 percent.
All
individual results are within 10.0 percent (absolute) of the mean of the
results.
If
samples do not meet these criteria, we recommend that you investigate the
failure according to
the
flow chart in Attachment 1. We also recommend that you not proceed any further
with
implementation
of the methods described in this guidance until the criteria are met.
Sampling
errors may occur in some powder blends, sampling devices, and techniques that
make
it
impractical to evaluate adequacy of mix using only the blend data. In such
cases, we
recommend
that you use in-process dosage unit data in conjunction with blend sample data
to
evaluate
blend uniformity.
Some
powder blends may present unacceptable safety risk when directly sampled. The
safety
risk,
once described, may justify an alternate procedure. In such cases, process
knowledge and
data
from indirect sampling combined with additional in-process dosage unit data may
be
adequate
to demonstrate the adequacy of the powder mix. Data analysis used to justify
using
these
alternate procedures should be described in a summary report that is maintained
at the
manufacturing
facility.
As
an alternative, you can substitute the procedures described in the PDA
Technical Report No.
(see
reference in footnote 8) to ensure that the blend is uniform and that the
method meets or
exceeds
the criteria described above.
QUS37 PROBLEMS
AND SOLUTIONS IN TABLETTING.
ANS (1) SOURCES
OF PROBLEMS
FORMULATION
MACHINE
PROCESS
(2) TYPE
OF PROBLEMS
CRITICAL
1.DISSOLUTION
2.ASSAY
&UNIFORMITY OF CONTENT.
3.DISINTEGRATION
TIME.
4.WEIGHT
VARIATION.
NONCRITICAL
1.APPEARANCE
(CAPPING, LAMINATION, PICKING, STICKING,
CHIPPING,
MOTTLING, DOUBLE IMPRESSION)
2.HARDNESS
AND THICKNESS
3.FRIABILITY.
(3)
CAPPING AND LAMINATION:
CAPPING IS A
TERM USED TO DESCRIBE THE PARTIAL OR COMPLETE SEPARATION OF TOP OR BOTTOM CROWNS OF THE TABLETS
FROM MAIN BODY OF TABLET.
LAMINATION IS A
TERM USED TO DESCRIBE
THE
SEPARATION OF TABLET INTO TWO OR MORE DISTINCT LAYERS.
PROBABLE
CAUSES &SOLUTIONS OF CAPPING & LAMINATION:
·
AIR ENTRAPMENT DURING COMPRESSION
ELIMINATED
BY:
1.SLOWING
RPM OF MACHINE
2.REDUCING
FINAL COMPRESSION PRESSURE
BOTH OF
THIS GIVES TIME FOR STRESS RELAXATION
·
LESS MOISTURE CONTENT
DRY GRANULES TEND TO CAP AND
LAMINATE HENCE CORRECT MOISTURE SHOULD BE THERE FOR GOOD COMPACTION.
·
DEEP CONCAVE PUNCHES TEND TO MORE CAP
&LAMINATE
ELIMINATED
BY USING FLAT PUNCHES DURING FORMULATION & DEVELOPMENT
·
TABLET TOOLING
1.CONCAVE OR BEVELLED EDGE
PUNCHES SLIGHTLY INCURVED INSIDE FORM A CLAW
& PULLS IT OUTSIDE LEAD TO CAPPING & LAMINATION.
2.WEAR IN UPPER PUNCH GUIDE
ACCLERATES CLAW FORMATION BY PERMITTING PUNCHES TO STRIKE WITH EDGES OF
DIEHOLE.
3.GERATER
RADIUS OF CURVATURE OF PUNCH FACE.
·
DIE DEVELOPS A WEAR RING AT THE AREA OF COMPRESSION, WHICH
ENLARGES GRADUALLY.
ELIMINATED
BY
1.TURNING
OVER THE DIE AND CHANGING THE COMPRESSION POINT.
2.USING
DIES WITH TUNGUSTON CARBIDE INSERTS.
3.WEAR OF TOOLS INCREASES
WITH HARDNESS OF MATERIAL BEING
COMPRESSED INCREASES.BY KEEPING HARDNESS LOW THIS PROBLEM CAN BE PREVENTED.
·
SETTING OF EJECTION POINT AND SWEEP OFF BLADE
IMPROPER SETTING OF BOTH LEADS TO
BREAKING OF TABLET AS PROPER EJECTION OF TABLET NOT OCCURES.
ELIMINATED BY PROPER SETTING OF
BOTH.
·
JAMMING OF LOWER PUNCHES
THIS
RESULTS IN IMPROPER EJECTION OF TABLETS.
ELIMINATED BY PROPER LUBRICATION
& FREE FALLING PUNCHES.
(4)
PICKING AND STICKING:
PICKING TERM
USED FOR SURFACE MATERIAL OF TABLET THAT IS STICK TO AND BEING REMOVED FROM
TABLET SURFACE BY PUNCH, WHICH IS PARTICULARLY CONCERNED TO ENGRAVED PUNCHES.
STICKING TERM
USED FOR TABLET MATERIAL ADHERING TO THE DIE WALL CAN ALSO APPLICABLE TO BUILD
UP OF MATERIAL ON PUNCH FACE.
SERIOUS STICKING AT EJECTION CAN
CAUSE CHIPPING OF TABLET EDGE &CAN PRODUCE ROUGH EDGE.
THIS MAY RESULT IN WEAR OF CAM
TRACKS &PUNCH HEADS AS PUNCH MOVEMENT IS NOT FREE IN DIES.
PROBABLE
CAUSES & SOLUTIONS OF PICKING & STICKING
·
ENGRAVED PUNCHES HAVING LETTRS LIKE `B’ ,`A’
&`O’.
ELIMINATED BY ENGRAVING IN LARGE
LETTER SIZES & FORMULATING TABLET IN
LARGER SIZES.
·
ROUGH SURFACE OF PUNCHES
ELIMINATED
BY 1.POLISHING THE PUNCHES
2.CHROMIUM PLATING OF PUNCHES
ADDING COLLOIDAL SILICA IN
FORMULATION WHICH REDUCES ADHERANCE OF MATERIAL TO DIES AND PUNCHES.
CHANGING
BINDER OR INCREASING BINDER PERCENT.
EXCESSIVE
MOISTURE CONTENT.
MAINTAINING
TEMP.& HUMIDITY IN CASE OF LOW MELTING POINT INGRADIENTS.
(5)
MOTTLING:
MOTTLING TERM
USED FOR UNEQUAL DISTRIBUTION OF COLOUR ON TABLET SURFACE.
PROBABLE
CAUSES AND SOLUTIONS:
1.DRUG OR IT DEGRADATION PRODUCT
HAVING DIFFERENT COLOUR FROM ADDETIVE. ELIMINATED BYADDING COLOUR TO
FORMULATION.
2.MIGRATION
OF COLOUR DURING DRYING
ELIMINATED
BY
CHANGING
SOLVENT SYSTEM
CHANGING
BINDER
REDUCING
DRYING TEMP.
MAKING
SMALLER PATICAL SIZE.
(6)
WEIGHT VARIATION :
THE WEIGHT VARIATION OF TABLET IS
DECIDED BY GRANULES FILLED IN DIE PRIOR
TO COMPRESSION. ANYTHING THAT ALTERS THE
DIE FILLING PROCESS ALTERS TABLET WEIGHT
PROBABLE
CAUSES & SOLUTIONS .
1.GARNULE
SIZE & SIZE DISTRIBUTION BEFORE COMPRESSION.
2.POOR
FLOW
ELIMINATED
BY
-REDUCING MACHINE RPM
-BY ADDITION OF GLIDANT LIKE TALCUM
&COLLOIDAL SILICA.
-USING
FORCE FEEDER
-GEOMETRY OF HOPPER FOR
ELIMINATING RAT HOLING & BRIDGING.
POOR MIXING – ELIMINATED BY
THROUGHLY DITRIBUTION OF GLIDANT& LUBRICANTS BY SETTING PROPER LUBRICATION
TIME.
PUNCH
VARIATION –PUNCH HEIGHT VARIATION MAY LEAD TO WEIGHT VARIATION.
(7)
HARDNESS VARIATION:
§THIS IS
DIRECTLY RELATED TO WEIGHT VARIATION
§DISTANCE
BETWEEN UPPER & LOWER PUNCHES VARIES HARDNESS VARIES.
(8)
DOUBLE IMPRESSION:
THIS INVOLVES TABLETS HAVING
MONOGRAMS & BREAKLINE
PROBABLE
CAUSES
ØDUE TO
FREE FALL OF PUNCHES SOLVED BY TIGHTING PUNCHES BY ANTITURNING DEVICE.
ØIMPROPER
SETTING OF LOWER GUIDING CAM.
9) Ridging : Ridging occurs on
the edges of the tablets and is characterizes by the buildup of material around
the edge which present the rough
appearance.
10) Split : if less than app.¼ of the cap length.
11) rough cut : if less than app. 1/8of the circumference. and ¼ of the
cap length.
(9)
PROBLEMS IN FILM COATING
STICKING
& PICKING
ROUGHNESS
ORANGE
PEEL EFFECT
BRIDGING
& FILLING
BLISTERING
COLOUR
VARIATION
CRACKING
VERY
–VERY IMPORTANT TIPS FOR FILM COATING SUGGESTED BY COLORCON:
FOR
AQUOUS COATING:
·
80 to 120g solution / minute/
spray gun should be applied.
·
Total coating time should be
between 100 to 120 minutes.
·
Atomizing air pressure should be
between 0.15 to 0.2mpa to avoid spray drying.
·
Differential pressure should be
such less that heavy dusting is observed in pan.
Differential pressure should be such excess that sprays drying
occur.
So Negativity in pan should be such that facilitate the proper
spray on tablets bed.
·
Outlet temperature should be
above 42 degree centigrade to avoid the wetting of tablet bed.
·
Spray pattern should not be more
divergent because it can cause the overlapping of the sprays of the both the
gun.
·
Spray pattern should not be more
convergent because it can cause the heavy pressure on tablet bed resultant
dissolving of tablets.
·
Bed distance should be between 19
to 20 cm.
FOR
NON-AQUOUS COATING:
·
140 to 200g solution / minute/
spray gun should be applied.
·
Total coating time should be
between 50 to 70 minutes.
·
Atomizing air pressure should be
between 0.10 to 0.2 mpa to avoid spray drying.
·
Differential pressure should be
such less that heavy dusting is observed in pan.
Differential pressure should be such excess that sprays drying
occur.
So Negativity in pan should be such that facilitate the proper
spray on tablets bed.
·
Outlet temperature should be
between 35 to 41degree centigrade to avoid the spray drying due to high
temperature (High temperature cause solvent evaporation)
·
Spray pattern should not be more
divergent because it can cause the overlapping of the sprays of the both the
gun.
·
Spray pattern should not be more
convergent because it can cause the heavy pressure on tablet bed resultant
dissolving of tablets.
·
Bed distance should be between 16
to 19 cm.
Model of film coating machine : SFC 60
SFN ,28.0L ,10-17 kg
SFC 130 SFN ,225.0L ,120-200 kg
DFH 1700, 930 LT(300 – 500) kg
Area qualification following points r
checked :
1)Microbial
count : air sample ( 190 /200 CFU),settle plate(90/100 CFU),RODAC Plate (40/50
CFU) testing r carried out at 20 – 25
degree centigrade for 72 hrs and 30 – 35
degree centigrade for 48 hrs, soyabin casin &agar agar r used for
media it’s frequency is first weekly then
monthly.
2) light intensity ( NLT 200 lux or depend on the activity )
3) Sound level at Dynamic condition (NMT 80 db)
4) pressure difference : NLT 6 pascal
5) Temperature & Humidity
NMT25 degree centigrade NMT 55 % Rh
6)Air Change
: NLT 20 Cycle , two type of air flow in area 1) Uni-directional
/ laminar
displacement
of dirty air
2)Turbulent dilution
of dirty we follow turbulent type air
flow.
6)
7) Partical count In Cubic meter : For A grade In ISO 5 - at rest condition 100 paritcal
of 0.5 micron and 0 partical of 5 micron . At dyanamic condition it will same
For B grade In ISO 5 - at rest
condition 100 paritcal of 0.5 micron and 0 partical of 5 micron . At dyanamic condition 10000 paritcal of 0.5 micron and 57
partical of 5 micron
For C
grade In ISO 7 - at rest condition 10000 paritcal of 0.5 micron and 57
partical of 5 micron . At
dyanamic condition 100000 paritcal of 0.5 micron and 570 partical of 5
micron
For A
grade In ISO 8 - at rest condition 100000 paritcal of 0.5 micron and 570
partical of 5 micron . At
dyanamic condition is not define
HVAC ( Heat ventilation and air
condition system): if the difference pressure across the hepa filter is below
70 pascal that means hepa choke and its required to change, If the total
repaired area is 3% of the total filter area in this condition it is required
to replace.
MOC of HEPA : glass micromic fiber
Size of HEPA 0.03 micron &
efficiency is 99.97 %
RTD
: Resistance temp. indicator
RPM of chopper 1500(slow)/3000(fast)
RPM of better 56(s)/110(f)
Motor........
FBD : Exhaust
blower 6500/4000 CFM( 40 HP), FBD bag having
1+6+11=18 finger
Equipment capasity : 30% Minimum
& 80 % Maximum at 0.5 bulk density
Process
validation :
It is done for new product ( prospective validation )
in
Granulation Sampling(BUA) will be done in RMG( 10 Location) and Blender( 10
Location). Sample Qty is 2 to 3 times of
average weight . As per our procedure
we stop the activity till RMG result comes . As soon as result of final blending come we
start compression in the compression following sampling done
High speed,low speed,optimum speed,high
hardness,low hardness,full hopper,half hopper ,Start,middle ,end .
Three continue batch
r require for process validation.
Optimization batch :this batch is required for optimize the parameter , it may full
commercial batch size or 1/10 of
commercial batch( depend up on facility u have),it may more then one
batch,It can be sell after receiving the Accelerated study
data(40 +/- 2 deg.cen. And 75% +/- 5% rh
period 0,1,2,3,6, month). long term study( 25 +/- 2 deg.cen.
& 60% +/- 5% rh period
0,3,6,9,12,18,24,36,48,60 month) intermediate (30 +/- 2 deg.cen. &
65% +/- 5% rh period 0,3,6,9,12, month )
Concurent
validation/ re validation: No prospective validation , change in batch
size,precess parameter,critica equipment,formula, physical parameter like
particalsize,Bd,
Retrospective
validation. : For the product which r running at least 3 years ,for which
pro.&con. Validation is not done and shall be deliverd by using analytical
or other quality parameter (APR). On the basis of observation finding in
APR(annual product review) concurent validation may plan.
URS ---
DS/FS -----DQ ---- BULIDUP-----FAT---SAT----IQ---OQ---PQ
TOTAL STAFF-180-190,WRKMEN-350
Cleaning validation : the sampling
point will be hard to clean surface. The purpose of cleaning validation is to
the check efficiency of cleaning procedure. The study will be done on wast
case, which is select on the basis of
following high potent drug ,hard to
clean,,low mar value,least therapeutic dose . We take two criteria 1) dose base
for that we used following formula for calculating MAR. 2) 10 PPM.
two type of paper r used for swap. First
watmen and alpha wipe. It will be selected on the basis of recovery(70%). Three
type of template r used 10*10,5*10,5*5 cm. We select the template on the basis
of feasibility .
Three method r used to analysis the
sample 1)TOC 2) HPLC 3) UV But we used
the TOC method because is gives the total carbon of API along with expients
wheres HPLC Gives only Total carbon of API.
MAR Value =
Minimum lenthal dose* minimum batch size in the equipment(150.00Kg)*1000 / maximum
daily dose(4000 mg)* safety factor(1000)
Therapeutic dose : Minimum qty of API which produce any effect in
our body .
Lenthal dose : Minimum
qty of API which kill the 50 % of micro organism
Safty factor : 1 part of the previous product of drug is
allow in the 1000 part of next product.
Compressed air : test
perform by gather in our company. 1000
Lt air is passed through caco3 bed the check the weight. Of bed before & after and calculate the moisture % . it
should be dry as we have drier.
Criteria
of cleaning validation :1) physical checking 2) dose base : a) 10
ppm b) 0.1 % 3) Toxicity base: for that
whose dose value r not known like vitamin.
Limits of
weight variation : out of 20 tablets 2 tabs
may be fail but both the tabs should come +/- 2 time of the limit.
Other wise fail then check the weight
variation of 40 tabs in this condition 6
tabs may fail but 6 tabs should come in
+/- 2 time of limit.
Limits of
thickness : +/- 5 %
Weights : < 80 mg 10
% , 80mg
to 240 mg is 7.5 % , 240 mg < is 5%
Assay : 95% to 105 %
DR
limit(USP) : If Q is 80 % which is standard ,
S1
--- check the DR of 6 tabs ,
each unit is not less then Q+5%
S2 --- Again check the DR of 6 tabs, Av . of 12 tabs (S1+S2) is equal to or grater
then Q and no tablets
is less then
Q-15 %l
S3 --- Again check the DR of 12 tabs, Av .of 24
tablets (s1+s2+s3) is equal to or grater then Q and not
not more
then 2 tablets is less then Q-15 % and
no tablets is less then Q-25 %
Friability : 6.5 g
taken as it is given is USP or nomal
induatrial practice
Capasity of block : 1.0 Bilion( old Block ) 2.0 Bilion ( New
block ) 0.5 bilion ( amo)
Limits : Milled
grs 94 to 102 %
Lubricated grs 94 To 102 %
Com. Tabs (Yield) 95 To 102 %
Processing yield 94 to 102
%
Guide line :
ICH(international
conference for harmonization) Guide line : This Guide also known as tri
partic guide line because it is
harmonize by three country ( Europe ,japan, USA) . Most of the country use this
guide line for Stability or other.
USFDA ( 2 years) : It
is quality based audit it intention to check the system
210
---- GMP for API division(
210.1,210.2,210.3 subpart)
210.1---- CGMP
210.2-----Applicbility of CGMP
210.3--- Defination
211 -----
Gmp for Formulation ( A ,B, C, D, E, F, G, H, I, J, K)
A----- General provisions
B----
Organization and personnel
C--- Building and
Facilities
D----
Equipments
E---
Control of component and drug product container and closer
F-
Production and process control
G-----
Packing and label control
H--
Holding distribution
I----
Lab rotatory control
J---- Record and reports
K--- Return and salvage drug
product
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