Interview Question

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