SELECTION OF THE WORST CASE AND

ACCEPTANCE CRITERIA FOR THE

CONTAMINATION

    8.1    MAXIMUM ALLOWABLE
CARRYOVER (MACO)

                                TD X BS X SF
             MACO =   ……………………
                                      LDD         

Where,
MACO   : The maximum allowable
carryover of previous product into next
product.
TD         : Minimum therapeutic dose of
previous product A.
BS         : Batch Size of the next product.
SF         : Safety factor (1/1000)
LDD      : Largest daily dose of the next
product.
             

A)  For Swab,
    

             mg of permissible active per

swab   =        MACO  X  Swab Area  
                                                                    
         -----------------------------------
         
Common Surface Area

B) Maximum Allowable residue per swab

    

based on 10 ppm Criteria, mg of

permissible active per swab      
                            10 X B S (kg)
 =                     --------------------------- X
Swab Area
                             Common Surface Area

9.0              ACCEPTANCE CRITERIA:

A. For Visual Inspection Criteria:

    

 There shall not be any visual evidence of

         

previous product on the product contact

parts and other equipment surface after
cleaning.
 
B. 10 ppm Criteria:
     

 Not more than 10 ppm of previous

         

product residue shall appear in the Next

Product.

C. 0.001 % Dose Criteria:

    
  Not more than 0.001 % of previous
         

product residue shall appear in the

maximum daily dose of the next product.

D. For Microbial Contamination:

    

Sr. Swab Acceptance limit

 
No. Sample
01 Total NMT 100 CFU/Swab
Bacterial
Count
02 Total NMT  10  CFU/Swab
Fungal
Count
              Based on these acceptance
criteria lowest value shall be
considered for determination of
cleaning validity.

Cleaning Procedure: Reference SOP

            

(Page No. 7/17) & SOP No. PRT-022

 10.0    SAMPLING PROCEDURES &
SAMPLING PLAN:

I. SAMPLING PROCEDURE
                                      

 Prior to swab sampling, cleaned

         

equipment shall meet “Visual Clean”

criteria.
 After cleaning of the equipment visual
         

inspection shall be done and reported in

report.
 After Visual Inspection is found
         

satisfactory sampling shall be carried out.

 Use Hand gloves and mask during
         

sampling.

A).  For Swab Sampling:

Soak the swab for about 10 minutes in Purified water in a test tube. Swab the area of not less

than 100 cm2 and transfer the swab back into the test tube containing Purified water and cover

the same. Sonicate the test tube for about 2 minutes and filter the solution
 The Swabbing shall be done in horizontal
         

or vertical strokes like below shown

procedure in the marked area assuring
that the entire area is swabbed.
 
            

            

            

         

After swabbing, rinse the swabbing location by

        

purified water to remove the traces of solvent.

         through Whatman No. 2 filter paper.
          B).   For Rinse Sampling:
 Rinse the entire equipment with the
         

specified quantity of the Purified water

and collect the rinse in a clean container.
Remove appropriate quantity of rinse
sample and filter through Whatman No. 2
filter paper.
                  Prior to sampling, cleaned
equipment shall meet “Visual Clean”
criteria.
Sampling shall be carried out as per
current version of SOP No. SQA- 075
according to sampling diagram attached
in the Annexure I. Number Of locations
shall be sampled as mentioned below.   
  
II. SAMPLING PLAN:
            

a. Swab sample for chemical/Microbial

      

analysis
 Product Contact Sampling Locations Total
Name of
Surface Area Nos. of
Equipment
(In cm2) Swabs

 Outlet of feeder hopper (S3)

Sifter 100  Inner Surface of Sifter Bowl (S4) 4

 Sifter Sieve surface (S5)

        Gasket of Sifter Ring (S6)

 Discharge Valve (S7)

Rapid Mixer
100
 Below the chopper (S8)
4


Granulator    (RMG)
Below the Mixer  (S9)

  Gasket (S10)

 Discharge Chute(S11)

FBD/FBP 100
 Upper Plenum(S12)
4

 Product Bowl Sieve(S13)

 Bowl(S14)
       Blades of multimill (S15)
Multimill 100 2
        Sieve of multimill (S16)

 Side Wall Corner  (S17)


Blender 100 3
Discharge Port  (S18)
        Gasket (S19)


Compression 100 5
Machine Die Cavity of Turret (S20)

 Discharge Chute (S21)

 Inner Surface of Hopper – (S22)

  Punch Tip – (S23)

 Inner Surface of Die – (S24)

b. Rinse Sampling For Chemical/

      

Microbial Analysis

Name of Equipment Sampling Locations Quantity of rinse (ml)

Collect the 500 ml rinse samples after rinsing the

FBD/FBP Outlet of hose pipe (R1) equipment with purified water.

Collect the 500 ml rinse samples after rinsing the

Compression machine
Outlet of hose pipe (R2) equipment with purified water.

III. SAMPLING PLAN FOR CHEMICAL

            

ANALYSIS
(NON CONTACT PARTS):
 Swab Location Sample No

Wall NC 1
Ceiling NC 2
Return Grill NC 3
Wall NC 4
Ceiling NC 5
Return Grill NC 6

CHEMATIC DIAGRAM WITH SAMPLING

LOCATIONS FOR EQUIPMENTS:

a) SIFTER
      
b) RMG
     

c) FBP/FBD