SOP on Container Closure Integrity Testing (CCIT) for Dry Powder for Injection

SOP on Container Closure Integrity Testing (CCIT) for Dry Powder for Injection

1.0 Objective

1.1 To lay down the procedure for performing Container Closure Integrity Testing (CCIT) for Dry Powder for Injection using Chemical (Dye Ingress) Method and Microbial Challenge Study.

2.0 Scope

2.1 This SOP is applicable to Container Closure Integrity Testing of Dry Powder for Injection products manufactured and tested in the Quality Control Laboratory.

3.0 Responsibility

3.1 Officer or above – Microbiology Laboratory: Execution of the procedure and documentation.
3.2 Head – Microbiology Section: Review of test results and ensuring compliance with the procedure.

4.0 Accountability

4.1 Head – Quality Control: Overall compliance and approval of records.

5.0 Procedure

5.1 Chemical Method – Dye Ingress Method

(Dye solution outside the vials)

5.1.1 Preparation of Dye Solution

a) Prepare 3 liters of 5.0% Methylene Blue dye solution in a clean stainless steel (S.S.) vessel.
b) Transfer the prepared dye solution into the vacuum leak test apparatus.

5.1.2 Test Procedure

a) Submerge seven (7) intact vials containing Dry Powder for Injection into the dye solution.
b) Operate the vacuum leak test apparatus as per SOP  (Operation of Vacuum Leak Test Apparatus).
c) Apply and maintain a vacuum of 15 inches of Hg for 3 minutes.
d) After releasing the vacuum, keep the vials immersed in the dye solution for an additional 5 minutes to allow equilibration with external pressure (assuming potential leakage through the container closure system).
e) Remove the vials and rinse externally, if required.

5.1.3 Controls

a) Negative Control: Unchallenged (untested) intact vial.

5.1.4 Observation

a) Examine each vial individually against an illuminated dark background.
b) Observe for the presence of dye inside the vial.
c) Compare the test vials with the negative control.

5.1.5 Acceptance Criteria

a) No dye should penetrate into intact vials.
b) Presence of dye inside the vial indicates failure of container closure integrity.

5.1.6 Documentation

a) Record observations as per Format .

5.2 Microbial Challenge Study

5.2.1 Entry Procedure

a) Enter the Microbiology (MLT) room as per SOP.

5.2.2 Preparation of Microbial Suspension

a) Prepare Escherichia coli suspension (ATCC 8739) having a concentration of approximately 10⁶ CFU/ml as per SOP .

5.2.3 Challenge Procedure

a) Immerse twenty (20) intact Dry Powder for Injection vials in a container containing E. coli suspension (approx. 10⁶ CFU/0.1 ml).
b) Keep the vials immersed for four (4) hours.
c) After immersion, remove the vials and disinfect the external surface using 70% IPA.

5.2.4 Sterility Testing

a) Enter the sterility testing room as per SOP.
b) Transfer the disinfected vials through the pass box.
c) Perform sterility testing as per procedure GTP.

5.2.5 Controls

a) Negative Control: Unchallenged intact vial.

5.2.6 Incubation

a) Remove canisters from the drain tray.
b) Incubate at 30°C to 35°C for 72 hours.

5.2.7 Observation

a) Observe for any microbial growth after incubation.
b) Record observations as per Format .

5.2.8 Acceptance Criteria

a) There shall be no microbial growth after incubation at 30°C to 35°C for 72 hours.
b) Presence of growth indicates failure of container closure integrity.

6.0 Annexures

Annexure – I: Dye Ingress Method Record 
Annexure – II: Microbial Challenge Test Record

Annexure – I
Dye Ingress Method Record

Dye Ingress Method

Indicator Used: _______________________________

Indicator Concentration: _______________________

Product Name: ________________________________

Batch No.: ___________________________________

Number of Vials Taken: ________________________

Vial Size / Type: ______________________________

Date: ________________________________________

Observation Record

Negative Control: Unchallenged vial

Acceptance Criteria

The dye solution shall not penetrate through any intact vial when examined visually against an illuminated dark background for the presence of dye. Test vials shall be compared with the unchallenged (negative control) vial.

Any presence of dye inside the vial shall be considered as failure of container closure integrity.

Remarks:

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Done By / Date: ___________________________  Checked By / Date: _________________________