AQL (Acceptable Quality Levels) for all Lyophilized injectable Products

What is Acceptable Quality Level (AQL) :

Acceptable Quality Level (AQL) is a percent defective that is the base line requirement for the quality of the product. The sampling plan required to be prepared or design in such a way that there is high probability of accepting a lot that has a defect level less than or equal to the AQL.

Procedure :

  • After completion of Visual inspection, all the inspected vials shall be re-inspected for its physical defects and shall be evaluated for AQL prior to batch packing operation.
  • Clean the unlabelled vials with lint free cloth to remove any adhering particles or oily substance.
  • Check the vials for different type of rejects as per following sequence but not limited to:
  1. Volume rejects

                           a) Low fill.

                           b) High fill.

.                     2. Broken vial rejects.

                      3. Sealing rejects                       

                      4. Melt back rejects.

                      5. Glass particles

                      6. Particulate matter rejects

                           a) Black particles.

                          b) Fiber particles

                           c) White particles in lyophilized vials (in case of colored cake)

                           d)  Fiber particles (in case of colored cake)

                           e) Red particles

                      7. Abnormal Spots of filled and sealed vial

                      8. Others

Reference Vial selection (Dry Powder & Lyophilized vial):  

Randomly select 20 vials and place all the vials on plane surface and check the powder height. In case of Lyophilized vial check the cake height. Select the vial as reference having a height in maximum no of vials. Label the vial as reference vial.

Description of Rejects :

Sealing rejection : Check visually the vials for any type of sealing reject.  If found, separate the vials  as sealing rejects.

 Broken vial rejection : Check the vials for any type of breakages on the vial surface. If found, separate them as broken vial rejects.

Low fill rejection: Compare the vials for cake height with the reference vial. If the height is found to be lower than the reference vial separate those as low fill rejects.

 High fill rejection:  Compare the vials for cake height with the reference vial. If the height is found to be higher than the reference vial separate those as high fill reject.

Melt back rejects : Check the vials for any type of change in cake shape and size, any shrinkage in cake or cake collapsing. Check the vials for presence of moisture and water also. If found, separate vials as melt back rejects.

Black particle rejection : Check the vials on the cake peripheral surface and vial surface from inside for black particles against white back ground. If found, separate the vials as black particle rejects.

White particle rejection : Check the vials on the powder peripheral surface and vial surface from inside for white particle against black back ground. If found, separate them as white particle rejects.

Red particle rejection : Check the vials on the cake peripheral surface and vial surface from inside for red particles against white background. If found, separate them as red particle rejects

Fibers (colored cake) : Check the vials on the cake peripheral surface and vials surface from inside for fibers against black back ground (for colored cake) If found separate them as fiber rejects

Keep the rejected vials with respect to the rejection type in designated place provided on the table and the operator shall collect the rejected vials separately in different crates / trays showing the status label as “REJECTED” and all the rejects shall be placed in Quarantine area.

During inspection process collect representative samples of required quantity in a separate crate / shipper as mentioned in the below table to cover entire inspection process i.e from Initial, Middle & End of the process and required quantity of samples shall be drawn for AQL inspection as per the below table and shall write all the details of AQL inspection.

The inspected vials shall be finally verified by QA person for critical, major and minor defects as per the below mentioned AQL level.

Acceptance criteria: 

AQL 0.01% for critical defects, 0.1% for major defects and 1.0 % for minor defects

Examples of Defects :

  • Critical Defects: Safety risk may cause permanent injury to patient.       

Examples of a Critical defect (Mentioned below but not limited to):

1. Cracks on glass / leakage of product from vial

2. Hidden cracks under the crimp

3. Particulate matter (glass particles)

4. Sealing defect

5. Incorrect product

6. Incorrect color

7. Presence of more than one product ( mix-up)

8. Empty vial ( with out product)

  • Major Defects: Functional risk, product impossible or difficult to use. Result in the patient being unable to obtain the dose of a non-life saving medicine.

Examples of a Major defect (Mentioned below but not limited to)

1. Crack in primary container of a sterile product.

2. Gross over or under fill of liquid injection or lyophilized injection.

3. Black particles, white particles, fibers

4. Molding defects

5. Powder spillage on the surface of the vial

Minor Defects: A defect which is cosmetic in nature:

1. Molding defects

2. Scratches          

3. Abnormal spots on filled and sealed vials

If any non conformity observed against the  specified AQL limits in any batch / lot , such entire batch  / lot shall be appropriately stored and affix “ Quarantine “ label until re-work plan for re inspection initiated and In case of any abnormality,” Under Hold” label shall be pasted on to the containers and the container shifted to the Quarantine area till further decision.

Investigation shall be initiated for the batches / lots those exceeds AQL limits before proceeding to  next processing stage and based on the investigation made the batch / lot  shall be re inspected for the whole batch / lot and the appropriate corrective actions shall be implemented.

In case the percentage of defects are found to be within the specified AQL levels, the IPQA executive shall  verify the AQL results and release the entire lot for next process stage.

The quantity withdrawn for the AQL check shall be added to a good vials of particular batch / lot and the approved good vials should be shifted to the approved quarantine area or to the labeling and packing area as per the requirement after pasting the proper status label.

You can also Read the AQL in Pharmaceuticals for Oral solid dosage form https://pharmaceuticalupdates.com/2020/02/23/acceptable-quality-level-aql-in-pharmaceuticals/

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