Tuesday , September 26 2023

Non Conformance and Failure Investigation Checklist in pharmaceutical Products

Non Conformance and Failure Investigation Checklist in pharmaceutical Products

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Product Name                :                                           Batch No.  :                               Batch Size   :

Manufacturing Date    :                                                                                                 Expiry Date:   

Investigators                  :

Investigation Started on   :                                                                         Investigation completed on:   

Suspected cause of product failure or NCR, if any :

S. No. Statement Observation Remarks
Checking of raw material(s) used for Batch Manufacturing and records
1. Check the receipt documents of the materials used for manufacture of the product under investigation:    
i.   Check the Goods-In-Inspection report for physical status of consignment received    
ii.  Verify if the materials, especially the active ingredient(s) have been received from approved vendors

a.       Does Store has a current list of Approved Vendors

b.       Has the API (s) been received from more than one approved vendor (especially supplier)? If yes, compare the consignments received w.r.t. :

–     Transportation chosen (measures taken by the transporters to prevent exposure of material to heat, humidity, light, etc.)

–       If the vendor is approved, has the vendor appraisal been conducted

iii. Check the environmental conditions in the quarantine area during storage of material(s)    
2. Does the Raw Materials Specification of the raw materials, especially the API include parameters like particle size, density, etc. in its specification?    
3. Check the raw material reserve / control samples in Quality Control for :

i.       Proper labelling

ii.     Proper Storage

iii.   Adherence to the Standard Operating Procedures for storage and withdrawal of control samples

4. Verify Standard Operating Procedures for accuracy of procedure, records maintained and operational status of the SOPs e.g. Material receipt, Dispensing and storage of materials, handling of etc.

i.      As on date of investigation

ii.    During period of manufacture of product under investigation

5. Are the materials available in Stores (both Raw Material and Packaging Material Store)

i.       Stored properly (isolated from floor and detached from the walls)

ii.    Properly Labelled

iii.  Stored as per recommended Storage conditions

iv.   Stored in the relevant areas

v.     Retested, where applicable, as per requirement and labelled accordingly

6. Check the raw material currently stored and sampled by QC for

i.      Proper labelling of the sampled containers

ii.    Proper Resealing of the sampled container

iii.  Inquire the QC Chemist for procedure followed for sampling

-Cleaning procedure of sampling aids

-Handling of material during sampling

iv.   Check the records maintained in QC for :

–    Date of receipt of sample in QC

–    Conditions during storage of material in QC

–    Date of release of

7. Check the calculation used for dispensing of active ingredient.

a. Has the calculation been checked by production personnel and verified by QC personnel?

8. Check the weighment sheet and issuance record for raw materials issued for manufacture of the product in the Store for :

i.        Quantities of materials dispensed

ii.      AR. No. of materials dispensed

iii.    Conformance of issuance of materials to FEFO

iv.     COA of materials dispensed and retest date (cross check AR. No. recorded in the issuance records, value of assay, water/ LOD, etc.)

9. Check the Dispending Booth Records at the time of dispensing for the product batch:

i.        Area Cleaning records

ii.      Line Clearance records

iii.   Cleaning records(of both Dispending Booth, dispensing aids and vessels/ containers in which the materials have been dispensed

iv.    Machine Log sheet

v.      Preventive Maintenance

10. Check the Status of balances used for dispensing of Raw Materials in Store for :

i.        Calibration Status

ii.      Cleaning Status

11. Has any material been released on deviation? If yes, verify:

i.      Reason of deviation

ii.    Deviation authorised by

12. If the material is still available in stores, check the following:

i.      Labelling on the containers

ii.    Retest date, if applicable on the label

iii.  Proper storage

13. Check the calibration records of :

i.        Balances used for dispensing

ii.      Hygrometer

iii.    Pressure gauges of the Dispending Booth

iv.    Master weight certificate (Issuance date:                         valid up to:                         )

14. Is the access to the printed packaging material store restricted?    
15. Does Store maintain list of persons authorised to entry areas with “restricted entry”?    
Checking of Manufacturing Operation and records
16. Verify Standard Operating Procedures relevant to different manufacturing operations. Are these ‘current’?

i.      As on date of investigation

ii.     During the period of manufacture of the product

17. Are the SOPs relevant to operations accessible and available for use?    
18. Are the equipment labelled according to their status and content?    
19. Is the manufacturing area clean?

i.      Check area cleaning records

ii.    Has the frequency of cleaning as per SOP

iii.  Has rotation of disinfectants implemented

iv.   Has the checking of area undertaken by IPQA as per frequency mentioned in the SOP

20. Check and record the following information w.r.t. product under investigation:

i.      Material dispensed on:

ii.    Batch manufacturing started on : (date)                                (time)

iii.  Storage conditions of materials during the period dispensed material was stored prior to the start of batch manufacturing

21. Observe the area environment conditions and cross check with the records.    
22. Select any machine e.g. blender, sifter, filling machine and check the following:

i.      Line Clearance record (cross check with the Batch Manufacturing Record of the previous product mentioned)

ii.     Preventive maintenance label and verify

iii.    Calibration records of instruments, where applicable

iv.    Qualification data

23. Check the Batch Manufacturing Record of the product under investigation

i.      For overwriting, cutting or any other indications suggestive of intentional change in data.

ii.     Environmental conditions at the time of manufacturing    
iii.    Check the equipment used for manufacture of the product for:

a.       Description/ capacity of equipment  as per BMR

b.      Line Clearance

c.       Calibration status of critical instruments, if applicable

d.      Preventive Maintenance Status

e.       Training records of the personnel who operated the machines at the time of manufacture of  the product (Select any three machines e.g. Compression/ Capsule filling/ Bottle filling, blender, FBD, etc.)

Machine name and code          Operator Name            Operator Name     Operator Name _________________       ____________           ____________   ____________

_________________       ____________           ____________   ____________

_________________       ____________           ____________   ____________


iv.    Are all the production stages entries signed by designated personnel?    
v.     Has the “on-line” in-process test undertaken by production personnel as mentioned in the BMR of the product?    
vi.    Has the sampling for in-process tests other than the above mentioned, been conducted by IPQA personnel?    
vii.   Check the In-process testing records for:

a.     Check if the parameters tested is an per specification or as mentioned in BMR.

b.    Check if the in-process request is signed and dated both by production and IPQA, as appropriate

c.     Check the raw data

d.    Is the analysis records signed by both person who executes them and an authorised person from QC

e.     Verify if the testing has been done as per Standard Testing Procedure

viii.  Has the thorough put time of the process gone beyond the normal judged time?    
ix.    Is the Process Capability Index, if any available for the product?    
24. Observe the Batch Manufacturing Record for duration for which various intermediates have been stored? Record few examples.

Stage                                        Process Completed on                           Next step started on ______________            ________________                       _________________

______________          _________________                       _________________

Does the period suggest any detrimental effect on the quality of intermediate e.g. de-blending?

25. Has difference between particle size of various ingredients evaluated during product development/ validation?    
26. Has Purified Water been used during manufacture of product? If yes, check:

i.        Sampling procedures followed

ii.      Testing records

iii.    Release reports

27. Does the product intermediates like blend, compressed tablets, etc. require specific storage conditions? If yes, then check the following:

i.    Storage Area environmental records for the period when the intermediate was stored

ii.  Period for which the intermediate was stored

iii.   Is the entry to the Intermediate storage area restricted

iv.   Is list of person(s) authorised for entry into restricted areas available

28. Is the packaging material stored in the designated area? Check the storage of issued packaging materials, especially printed packaging material, before use    
29. Check the packaging materials issued for the product for:

i.       Quantities issued

ii.      Stock register of stores for compliance to FIFO

iii.     Verification of Quantities by production after receipt of material in production

30. Is the entry to the Printed Packaging Material Restricted?    
31. Does Packaging Material Store Maintain a list of person(s) authorised for entry into restricted areas?    
32. Was line and area clearance done before start of printing and packaging operations?

Check the line clearance records of the packaging machine.

33. Verify

Time of issue of Packaging Material:                              Time of Start of Packaging Operation:

34. Has reconciliation of packaging material done after completion of batch?    
35. Has the returned packaging material adequately entered in the Store registers?    
36. Has destruction of packaging materials, especially printed packaging material, done under the supervision of IPQA personnel?    
37. v.     Check the Control Samples of the product

i.       Quantity of samples withdrawn

ii.      Physical condition of Control Samples

iii.     Condition of Control Sample storage area.

iv.     Is the access to Control Sample storage area restricted

38. Verify if the yields at different stages of manufacturing operations of the product.

i.If within the limit, compare the yield with at least preceding two batches and succeeding batch.

ii. If out of limit, has deviation been raised and investigated?

iii. Are any corrective and preventive actions taken?

39. Has deviation occurred during manufacturing? If yes, has deviation been raised?

i.     Deviation Report No.:

ii.    Has investigation been completed

iii.  If investigation is pending, reason:

40. i.     Date of transfer to Quarantine Finished Goods Stores:

ii.    Date of release of batch by Production:

iii.    Date of release of batch by QC:

iv.    Does the product has any microbiological testing? If yes, date of release of batch after       microbiological analysis:

v.     Date of despatch of first consignment and quantity:

41. Check the Distribution Warehouse for:

i.         Storage condition

ii.       Environmental conditions

iii.     Labelling

iv.      Segregation

42. Are temperature and relative humidity records available during the transit and transportation of the finished products?

–          If no, reasons thereof

–          If yes, are the conditions appropriate with the labelled storage conditions

–           Collect data of a period spreading across different season to obtain information regarding environmental conditions during transportation.

Other Queries  
43. What tests have been used to assess the uniformity of the final product? Verify the Content Uniformity/ weight variation testing?    
44. Check for a possible interactions between the process and its effect on the tablets compression e.g. tablet machine rpm on the dwell time and hardness or capping    
45. Does any ingredient in the formulation affects the density of the final blend to a greater extent than any other ingredient? If yes, does the specification ensures the density of such ingredient is well controlled?    

Note: Investigation shall not restrict to this checklist, it can go beyond it.


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About Pharmaceutical Guidanace

Ms. Abha Maurya is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 18 years of rich experience in pharmaceutical field. During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube

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