General Testing Procedure For PVC PACKING MATERIAL

    1.      Description:

PVC film of specification: - Non toxic transparent /nontransparent PVC. It shall be free from foreign matter, patches. It shall be wound on Aluminium / Plastic / Cardboard core without any loose pieces.
 2.      Width:
Ø  Take a sample of 1 meter from each roll if the no. of rolls is less than 5. If the no. of rolls is more than 5 then sample should be taken by the formula √n + 1.
Ø                  Measure the width by measuring scale at different places.
Ø            Take average of above readings. Tolerance: ± 1.0mm
 3.      Total Grammage:
Take 3 samples from 3 different rolls. Cut it to 05 X 05 cm, Weigh it and calculate the Grammage with following formula.
                              Weight of the piece in gm X 100 X 100                 =     −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−
                                                5.0    X      5.0 4.      Thickness:
Cut 5.0 X 5.0 cm Piece of the PVC film. Record the weight of this piece and thickness by the following formula.
                                                                                 X 10
                       Thickness of PVC =     ------------------------------- mm                                                                           X             X1.41Whereas 1.41 is specific gravity of PVC film

 

5.      Functional Test:
Take a roll of different specimen take trail on machine for the first consignment of Manufacturer or if any new manufacturer is there.
   
1.  Sealing – Check it for leakage.
2.  Blister formulation.
3.  Colour change during sealing.
 

6.      Shrinkage and Expansion Test of PVC Film:

Cut a piece of 10 x10 cm. accurately marking machine direction and web direction put this piece on a butter paper and Keep in an oven for 10 minutes the temperature  of which is set at 140°C. Remove the film and after attaining room temperature, measure the in both directions. The limits are as follows
 Shrinkages in machine direction …….7.0 % max.
Expansion in web direction      ……... 2.5 % max.
    After Treatment Wt:       =    −−−−−−−−−−−−−−−−−−−−−−− gm                                                               X 100 X 100Gram mage of PVC:       =    -------------------------------------    gm/m²                                                            X                                                                                                 X 100 X 100 Gram mage of PVC Layer (a -b):   =   ----------------------------------------------   gm/m²                                                                                            X   

General Testing Procedure For Printed Aluminium Blister Foil

Description:

An Aluminium Blister foil printed with text matter as per approved artwork and colour scheme.

Width:

Take a sample of 1 meter from each roll if the no. of rolls is less than 5. If the no. of rolls is more than 5 then sample should be taken by the formula √n + 1.

 Measure the width by measuring scale at different places.

Take average of above readings. Tolerance: ± 1.0mm

Thickness:

Measure the thickness by thickness gauge at different places.

Calculate the average of thickness note it.

Printing:

Check the printing of foil with approved artwork or approved specimen. Printing on sample foil shall match with approved specimen.

Measure the length (using a printing repeat length scale) from the beginning of the first eye mark to the beginning of the last eye mark.

Slitting:

                  Should be perfect without cutting of any text matter.

Text matter:

Compare the text mater at sample with Approved artwork or approved sample. If the text matter is similar to approved art work or sample then release the sample.

Colour scheme:

Check the colour of foil with approved shade card/approved sample. The sample colour should match with approved shade card/approved sample then sample is release. 

A.Total Grammage:

Take 3 samples from 3 different rolls. Cut it to 05 X 05 cm, Weigh it and calculate the Grammage with following formula.

                                       Weight of the piece in gm X 100 X 100

Grammage       =     −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− gm/cm²

                                                             5.0    X      5.0

B.  Grammage for 1^st poly / Alu. / 2^nd poly Foil:

1.   Take 3 samples from 3 different rolls, cut it to 05 x 05 cm, weigh it. Calculate the total Grammage with above formula.

2.   Then deep the piece into conc. Nitric Acid for 15 min. Poly layer get separate from Aluminium Foil and poly layer using filter paper. Weigh it.

3.   Calculate the grammage with above formula for all layers.

Scotch test:

No ink lifting from printed side on cell tape after removing the tape by 10 to 15 minutes from foil.

VMCH Coating:

VMCH is the Heat Seal Lacquer Coating given to the foil surface for Blister packing. Cut a Piece of 5.0 x 5.0 cm and weigh it calculate total grammage, then dip the piece into ethyl acetate, dry the piece and weigh again and take difference between these two weights which is the VMCH coating .Calculate the GSM of VMCH coating as per formula.  

Pin Hole Test:

Cut a one meter foil from the roll and check the pinholes on the foil by pin hole tester.

General Test Procedure For Oxidisable Substance

PROCEDURE 

To 100 ml of sample in 250 ml conical flask, add 10 ml of dilute sulfuric acid and 0.1 ml of 0.02M potassium permanganate and boil for 5 minutes. The solution remains faintly pink.

Preparation of Nitrate standard Solution (100ppm) for limit Test

PROCEDURE:
Dissolve and dilute 0.163 g of potassium nitrate to 100ml with water. Dilute 1 volume of above solution to 10 volumes with water.

Preparation of Nitrate Standard Solution (2ppm) for Limit Test

PROCEDURE:

Dissolve and dilute 0.163 g of potassium nitrate to 100ml with water. Dilute 1 volume of above solution to 10 volumes with water (100 ppm NO3). Dilute 1 Volume of nitrate standard solution (100 ppm NO3) to 50 Volumes with water.

Preparation of Lead Nitrate Stock Solution (1000ppm) for Limit Test

PROCEDURE:

Dissolve 0.4gm of Lead nitrate in water containing 2ml of nitric acid and add sufficient water to     produce 250.0ml.

Preparation of Iron Standard Solution (10ppm) for Limit Test

PROCEDURE:

Dissolve 7.022 g of ferrous ammonium sulphate in water containing 25 ml of 1M sulphuric acid and add sufficient water to produce 1000 ml. Dilute 1 volume to 100 volumes with water.

Preparation of Chloride Standard Solution (25ppm) for Limit Test

PROCEDURE:

Dilute 5 volumes of a 0.0824 % w/v solution of sodium chloride to 100 volumes with water.

Preaparation of Arsenic Standard Solution (10ppm) for Limit Test

PROCEDURE:

Dissolve 0.33 g of arsenic trioxide in 5 ml of 2M sodium hydroxide and dilute to 250.0ml with         water. Dilute 1 Volume of this solution to 100 volumes with water.

Preaparation of Ammonium standard Solution (1ppm) For Limit Test

PROCEDURE

Dilute 10.0 ml of a 0.0741% w/v solution of ammonium chloride to 25.0 ml with ammonia-free     water. Dilute 1 Volume of the resulting solution to 100 volumes with ammonia-free water, immediately before use.

                                                            

Preaparation of Lead Standard Solution (1ppm) For Limit Test

PROCEDURE:

Dilute 1 volume of lead standard solution (0.1 % Pb) to 10 volume with water (i.e.100 ppm  Pb), Dilute 1 volume of lead standard solution (100 ppm Pb) to 10 volumes with water (i.e.10 ppm Pb), further dilute 1 volume of lead standard solution (10ppm Pb) to 10 volumes with    water (i.e.1 ppm Pb).  

OR   Dilute 1ml of lead stock solution (1000ppm) to 1000ml with water.

Operating and temperature monitoring of incubator/BOD incubator

1.0       Objective

     To lay down a procedure cleaning, operating and temperature monitoring of incubator/BOD incubator.

      2.0        Responsibility

      Microbiologist/QC-Executive.

      3.0        Accountability

      Head-QC executive

      4 .0       Procedure 

      5.0       Operation

      5.1         BOD Incubators

     5.1.1      Connect the BOD incubator with main power supply.

     5.1.2          Switch ‘ON’ the incubator and observe the set value (SV) and process value (PV).

     5.1.3         Press up arrow ‘▲’or down arrow’▼’ then press ‘set (P) to set the desired temperature.

     5.1.4     Open the door of BOD incubator then open the inner Acrylic door and keep the material on the BOD                        incubator shelves.

      5.1.5    After keeping the material inside of the incubator, close the inner Acrylic door and then main door of                    BOD    incubator.

 5.2      Incubator

 5.2.1     Connect the incubator with main power supply.

 5.2.2     Switch ‘ON’ the incubator and observe the set value (SV) and process value (PV).

 5.2.3     Set the desired temperature by pressing◄ key and then increasing or decreasing the temperature by    using ▲ or ▼ key respectively.

 5.2.4     Open the door of incubator then open the inner Acrylic door and keep the material on the incubator   

               Shelves.

 5.2.5     After keeping the material inside of the incubator, close the inner Acrylic door and then main door of   incubator.

  5.3     Temperature monitoring of incubators and BOD incubators.

         5.3.1      Observe the temperature of BOD incubators and incubators once in a morning with calibrated                         thermometer and digital display of incubator.

Microbial analysis of oral suspension.

      1.0       Objective

     To lay down a procedure for microbial analysis of oral suspension.

      2.0        Responsibility

      Microbiologist/QC-Executive.

      3.0        Accountability

      Head-QC executive

                   Microbial Limit

                   Total bacterial count:100cfu/gm/ml

                   Total bacterial count:10cfu/gm/ml

      4.0         Procedure

          Total microbial count:

         Dissolve 10 g or dilute 10 ml of the preparation being examined, unless otherwise specified, in                     

          buffered sodium chloride-peptone solution pH 7.0 or any other suitable medium shown to have no              

          antimicrobial activity under the conditions of the test and adjust the volume to 100 ml with  

          the same medium. If necessary, adjust the pH to about 7.  

       4.1   Procedure for pathogen testing of oral Suspension

4.1.1    Transfer 10 mL oral suspension sample in 100 mL soyabean casein digest medium (SCDM).

4.1.2    After incubation, observe for growth in terms of turbidity, if it is observed perform pathogen testing.

         4.2     Tests for Escherichia coli (E. coli).

4.2.1    Transfer 1 mL of 24 hour old culture] suspension (SCDM) in 5 ml MacConkey’s Broth (MB) tube containing Durham’s tube and  incubate it at 42° to 44° for 24 to 48 hours.

4.2.2    After incubation, observe for purple to yellow color change of the MacConkey’s broth   with gas production in the Durham’s tube. If so, proceed with the following steps.

4.2.3    Subculture 1 mL of broth on a plate of MacConkey’s agar (MA) at 35° to 37° for 18 to 72 hours.

4.2.4    If growth of red, non-mucoid colonies is observed after incubation, then transfer 1 mL MacConkey’s broth in 5 mL peptone water (PW) tube and incubate at 42° to 44° for 18 to 24 hours.

4.2.5    After incubation, add 0.5 mL Kovack’s reagent into the above peptone water and if red color ring

                        appears the Indole test indicates the possible presence of E.coli.

4.2.6             Perform Gram staining of the colonies observed on MA .

4.2.7             Observe for presence of Gram negative rod.

 4.2.8         If Gram negative rod is present, streak loop full colony on Levin Eosin-Methylene Blue Agar   

                   (LEMBA) plate.

       4.2.9       Incubate this LEMBA plate at 35-37° C for 18 to 72 hours.

      4.2.10      After incubation, observe the plate and  if none of the colonies exhibits a characteristic  

                        metallic  sheen under reflected light, and if none exhibits a blue-black appearance under  

                       transmitted light, the test specimen meets the requirement for the absence of E. coli.

        4.3        Test for Salmonella Spp.

 4.3.1    Transfer 1 mL of 24 hour old culture] suspension (SCDM) in 10 mL Fluid Selenite Cystin Medium (FSCM) and        Tetrathionate Broth (TB) and incubate at 42° to 44° C for 18 to 24 hours.

4.3.2      Subculture on at least two different agar media chosen from agar media, Bismuth Sulphite Agar (BSA),                Deoxycholate Citrate Agar (DCA) and Brilliant Green Agar (BGA). Incubate at 35° to 37° C for 18 to

             72 hours.

4.3.3      The probable presence of salmonella is indicated by the growth of cultures having the  following  

              appearance:

                 BSA: well-developed, colour less colonies.

                 DCA: well-developed, red colonies, with or without black centers.

    BGA: small, transparent, colourless or pink opaque-white colonies often surrounded by a pink or

    red zone.

4.3.4     Perform Gram staining according to SOP  if the above characteristic colonies are observed.

4.3.5     If Gram negative rod is present, streak loop full culture from suspected colonies on Triple Sugar Iron (TSI) agar slant in tubes, using surface and deep  inoculation (stabbing) and incubate at 41° to 43° C for 18 to 24 hours.

4.3.6    The presence of salmonella spp. is confirmed if there is a change of color from red to yellow and usually a formation of gas, with or without production of hydrogen sulphide in the agar in the deep inoculation but not on the surface culture.

          4.4      Test for Pseudomonas aeroginosa

   4.4.1     Strick loop full of 24 hour old culture suspension (SCDM) on a plate of Cetrimide Agar (CA).

         4.4.2      Incubate this plate at 35 - 37° C for 18 - 72 hours.

  4.4.3     Perform Gram staining of the colonies observed on CA.

  4.4.4      Observe for presence of Gram negative rod.

  4.4.5     If Gram negative rod is present, streak representative suspect colonies from the CA plate on the surface   

               of  Pseudomonas fluorescin agar(PFA) medium for detection of fluorescin and Pseudomonas pyocyanin  

               agar (PPA)for detection of pyocyanin.

        4.4.6      Incubate these plates at 35° - 37° C for 48 to 72 hours.

  4.4.7     Examine the streaked surface of the both agar media under UV light, and interpret the results with  

               reference to the following table.

Selective Media	Characteristics	Fluorescence in UV light	Oxidase Test	Gram Staining
Cetrimide Agar	Generally Greenish	Greenish	Positive	Gram Negative rods
Pseudomonas Agar for detection of Fluorescin	Generally Colourless to yellowish	Yellowish	Positive	Gram Negative rods
Pseudomonas Agar for detection payocynin	Generally Greenish	Blue	Positive	Gram Negative rods

4.4.8     Oxidase disc test:

4.4.9    Transfer the colony from the PFA medium or PPA medium to disc that previously impregnated with N, N- dimethyl-p-phenylenediamine dihydrochloride.

4.4.10   If the disc colour is changed (from white to purple) within five to ten seconds it confirms the presence of

                 Pseudomonas aeroginosa.

        4.5       Test for Staphylococcus aureus:

4.5.1     Strick a loop full of 24 hour old culture suspension (SCDM) on a plate of Mannitol Salt Agar (MSA) (VPA) and Agar.

4.5.2       Incubate the plate at 35° to 37° C for 48 to 72 hrs.

4.5.3     After incubation, examine the streaked plates and interpret the results with reference to the following   table.

Selective Media	Characteristics	Gram Staining
VJA	Black colony surrounded by yellow zone	Gram positive cocci in cluster
BPA	Black, shiny colony surrounded by clear zone of 2 to 5 mm.	Gram positive cocci in cluster
MSA	Yellow colony surrounded by yellow zone	Gram positive cocci in cluster

       4.5.4     Perform Gram staining of the suspect colonies observed.

4.5.5    Observe for presence of Gram positive cocci in cluster.

4.5.6     If Gram positive cocci in cluster are present, perform coagulase test.

4.5.7     Take sterile test tubes each containing 0.5mL of mammalian, preferably rabbit or horse, plasma with or               without suitable additives.

4.5.8      Transfer representative suspect colonies from the surface of the VJA or MSA or BPA plate to the above               individual tubes and incubate in a water bath at 35° to 37° C.

4.5.9     Examine the tubes after 3 hours and at suitable intervals up to 24 hours. Compare the negative and                 positive controls.

4.5.10    If coagulation is observed, the specimen confirms the presence of Staphylococcus aureus.

microbial analysis of Hard gelatin capsule and tablets.

1.0       Objective      To lay down a procedure for microbial analysis of Hard gelatin capsule and tablets.       2.0        Responsibility       Microbiologist/QC-Executive.       3.0        Accountability       Head-QC executive                    Microbial Limit                    Total bacterial count:100cfu/gm/ml                    Total bacterial count:10cfu/gm/ml       4.0    Procedure        Water soluble product:          Dissolve 10 g or dilute 10 ml of the preparation being examined, unless otherwise specified, in                     buffered sodium chloride-peptone solution pH 7.0 or any other suitable medium shown to have no              antimicrobial activity under the conditions of the test and adjust the volume to 100 ml with the same medium.          If necessary, adjust the pH to about 7.          Product insoluble in water(non- fatty)-:        Suspend 10 g or 10 ml of the product to be examined in BP/W pH 7.0 or in another suitable liquid. In general a one            in ten dilution is prepared, but the characteristics of some products may necessitate the use of larger volumes.     A suitable surface-active agent such as 1 g/l of polysorbate 80 may be added to assist the suspension of poorly     wettable substances.     If the product is known to have antimicrobial activity, an inactivating agent may be added to the diluent.     If necessary adjust the pH to about pH 7.0 and prepare further serial tenfold dilution using the same diluents.     Homogenize and incubate at 35° to 37°C for not more than five hours.                      Testing of Pathogen          4.1   Procedure for pathogen testing of Tablets and hard gelatin capsule 4.1.1    Transfer 10 mL oral suspension sample in 100 mL soyabean casein digest medium (SCDM). 4.1.2    After incubation, observe for growth in terms of turbidity, if it is observed perform pathogen testing.                 4.2     Tests for Escherichia coli (E. coli). 4.2.1    Transfer 1 mL of 24 hour old culture] suspension (SCDM) in 5 ml MacConkey’s Broth (MB) tube containing Durham’s tube and  incubate it at 42° to 44° for 24 to 48 hours. 4.2.2    After incubation, observe for purple to yellow color change of the MacConkey’s broth   with gas production in the Durham’s tube. If so, proceed with the following steps. 4.2.3    Subculture 1 mL of broth on a plate of MacConkey’s agar (MA) at 35° to 37° for 18 to 72 hours. 4.2.4    If growth of red, non-mucoid colonies is observed after incubation, then transfer 1 mL MacConkey’s broth in 5 mL peptone water (PW) tube and incubate at 42° to 44° for 18 to 24 hours. 4.2.5    After incubation, add 0.5 mL Kovack’s reagent into the above peptone water and if red color ring                   Appears the Indole test indicates the possible presence of E.coli. 4.2.6         Perform Gram staining of the colonies observed on MA. 4.2.7        Observe for presence of Gram negative rod.  4.2.8     If Gram negative rod is present, streak loop full colony on Levin Eosin-Methylene Blue Agar (LEMBA)                plate.       4.2.9     Incubate this LEMBA plate at 35-37° C for 18 to 72 hours. 4.2.10 After incubation, observe the plate and if none of the colonies exhibits a characteristic metallic             sheen under reflected light, and if none exhibits a blue-black appearance under transmit light,                the test specimen meets the requirement for the absence of E. coli.         4.3        Test for Salmonella Spp.  4.3.1      Transfer 1 mL of 24 hour old culture] suspension (SCDM) in 10 mL Fluid Selenite Cystin Medium (FSCM) and Tetrathionate Broth (TB) and incubate at 42° to 44° C for 18 to 24 hours.  4.3.2     Subculture on at least two different agar media chosen from agar media, Bismuth Sulphite Agar (BSA),                Deoxycholate Citrate Agar (DCA) and Brilliant Green Agar (BGA). Incubate at 35° to 37° C for 18 to                72 hours. 4.3.3      The probable presence of salmonella is indicated by the growth of cultures having the  following                appearance:                BSA: well-developed, colour less colonies.                DCA: well-developed, red colonies, with or without black centers.   BGA: small, transparent, colourless or pink opaque-white colonies often surrounded by a pink or   red zone. 4.3.4     Perform Gram staining according to SOP if the above characteristic colonies are observed. 4.3.5     If Gram negative rod is present, streak loop full culture from suspected colonies on Triple Sugar Iron (TSI) agar slant in tubes, using surface and deep  inoculation (stabbing) and incubate at 41° to 43° C for 18 to 24 hours. 4.3.6    The presence of salmonella spp. is confirmed if there is a change of color from red to yellow and usually a formation of gas, with or without production of hydrogen sulphide in the agar in the deep inoculation but not on the surface culture.            4.4      Test for Pseudomonas aeroginosa  4.4.1     Strick loop full of 24 hour old culture suspension (SCDM) on a plate of Cetrimide Agar (CA).        4.4.2      Incubate this plate at 35 - 37° C for 18 - 72 hours.  4.4.3     Perform Gram staining of the colonies observed on CA.  4.4.4     Observe for presence of Gram negative rod.  4.4.5     If Gram negative rod is present, streak representative suspect colonies from the CA plate on the surface of Pseudomonas fluorescin agar(PFA) medium for detection of fluorescin and Pseudomonas pyocyanin agar (PPA)for detection of pyocyanin.         4.4.6     Incubate these plates at 35° - 37° C for 48 to 72 hours.   4.4.7     Examine the streaked surface of the both agar media under UV light, and interpret the results with reference to the following table. Selective Media Characteristics Fluorescence in UV light Oxidase Test Gram Staining Cetrimide Agar Generally Greenish Greenish Positive Gram Negative rods Pseudomonas Agar for detection of Fluorescin Generally Colourless to yellowish Yellowish Positive Gram Negative rods Pseudomonas Agar for detection payocynin Generally Greenish Blue Positive Gram Negative rods 4.4.8     Oxidase disc test: 4.4.9    Transfer the colony from the PFA medium or PPA medium to disc that previously impregnated with N, N- dimethyl-p-phenylenediamine dihydrochloride. 4.4.10   If the disc colour is changed (from white to purple) within five to ten seconds it confirms the presence of                  Pseudomonas aeroginosa.         4.5       Test for Staphylococcus aureus: 4.5.1     Strick a loop full of 24 hour old culture suspension (SCDM) on a plate of Mannitol Salt Agar (MSA) (VPA) and Agar. 4.5.2    Incubate the plate at 35° to 37° C for 48 to 72 hrs. 4.5.3     After incubation, examine the streaked plates and interpret the results with reference to the following table. Selective Media Characteristics Gram Staining VJA Black colony surrounded by yellow zone Gram positive cocci in cluster BPA Black, shiny colony surrounded by clear zone of 2 to 5 mm. Gram positive cocci in cluster MSA Yellow colony surrounded by yellow zone Gram positive cocci in cluster              4.5.4    Perform Gram staining of the suspect colonies observed. 4.5.5    Observe for presence of Gram positive cocci in cluster. 4.5.6     If Gram positive cocci in cluster are present, perform coagulase test. 4.5.7     Take sterile test tubes each containing 0.5mL of mammalian, preferably rabbit or horse, plasma with or               without suitable additives. 4.5.8     Transfer representative suspect colonies from the surface of the VJA or MSA or BPA plate to the above               individual tubes and incubate in a water bath at 35° to 37° C. 4.5.9     Examine the tubes after 3 hours and at suitable intervals up to 24 hours. Compare the negative and                 positive controls. 4.5.10   If coagulation is observed, the specimen confirms the presence of Staphylococcus aureus.