To lay down a procedure for handling of non-conformances.
This Standard Operating Procedure is applicable for handling of non-conformances associated with product (s) manufactured at pharmaceutical formulation plants.
Non-conformances observed in in-process products and Finished Products shall be handled through this SOP.
All HODs/ designee of the concerned departments shall be responsible for informing the non-conformances, if observed, in products.
Head, Quality Assurance or designee to investigate, and to decide about the disposition of non-conforming in process products or finished products.
HOD’s of concerned departments & QA Head shall be accountable for implementation of this SOP.
5.0 Abbreviations and Definitions
SOP : Standard Operating Procedure
QA : Quality Assurance
NCR : Non-conformance Report
Non-conforming product : Any product not conforming the established specifications and/ or not acceptable by virtue of its appearance/ physical state and/ or by virtue of other reasons which actually are not the part of set or established standards for that material.
Technical Committee : HODs or designee from the technical departments like QC, QA, R&D, and Production designated for investigating or giving opinion on the non-conformances.
6.1 If in-process product or Finished Product is non-conforming, then it shall be quarantined with distinct ‘HOLD’ label and shifted to the designated area under the supervision QA personnel.
6.1.1 Officer/ Executive of the concerned department shall raise NCR (Annexure-I ), mentioning description of non-conforming in process product or finished product.
6.2 NCR shall be sent to QA for further action.
6.3 In case of in-process product or finished product, Head-QA may constitute a technical committee who shall investigate the cause(s) of in process or finished product non-conformance. Refer Non Conformance Investigation checklist (Annexure-2), before further movement of the NCR to different departments.
6.3.Based on the findings of the investigations and/ or comparison with the specifications and / or validation data and / or product development report and / or sound scientific assessment and / or stability data with the product and / or the API molecule or the working experience with the similar kind of products or molecules, etc., by Head-QA and / or technical committee shall then give opinion on the non-conforming in process or finished product that whether the product can be :
- Re graded: Non-conforming product is reassigned for an alternate market or pharmacopeial compliance.
- Use as is: A non-conformance may be minor (no significant impact on product’s form or function) and it can be used as is.
- Rejected: Non-conforming products are rejected, when failing in critical or major test parameters that have significant affect on the product quality.
6.4 Concerned department shall give CAPA report, if applicable.
6.5 Following completion of investigation, each NCR shall be assigned a number by officer/ executive Quality Assurance, duly signed and dated. Each Non-conformance report shall have a nine-digit number the form NCRXXX/YY, where:
NCR – Denotes Non-Conformance Report
XXX – Serial number of the NCR
/ – “Slash”
YY – Last two digits of the year. i.e. 16 for 2016, 17 for 2017 etc. A new series of note shall be initiated every new year. The first NCR of the year 2015 shall be numbered as NCR001/15.
6.6 If non-conforming in-process product or finished product is rejected then the same shall be labeled with status ‘Rejected’ and handled as per SOP titled: Disposal of Non-Recoverable In-process materials and SOP titled: “Destruction of finished goods” respectively.
6.7 Based upon the investigation report head quality assurance or designee shall give his disposition on authorization of destruction of non-conforming in process or finished product.
6.8 After head quality assurance or designee’s disposition, quality assurance personnel shall send a copy of NCR to the concerned departments.
6.9 After disposition on NCRs, the same shall be reviewed on monthly basis by QA personnel and same shall be closed after verification.
7.0 Forms and Records (Annexures)
- Non-Conformance Report – Annexure-I
- Non Conformance Investigation Checklist – Annexure-II
- Non Conformance register – Annexure-III
- Flow Chart – Annexure-IV
- Master copy – Documentation Cell (QA)
- Controlled copies – Quality Assurance, Production, Quality Control, Finished Goods Warehouse, Raw Material Store, Packing Material Store
|Date||Revision Number||Reason for Revision|
Write ‘NA’ if not applicable; attach extra sheet if space provided below for recording is insufficient
|Specification No.:||STP No.:|
|Mfg. Date:||Exp. Date:|
|Description of Non-conformance:
Recorded by HOD/ Designee
|Investigation and finding Statements (Attach extra sheets if required):
CAPA required/ not required :……….
CAPA number (If applicable) :……………..
Signatures with date of Technical Committee Members:
Disposition by Quality Assurance:
Head Quality Assurance/ Designee
Re-evaluation of Non conformance required/ not required
|NCR No.: Sign: Date:|
|Authorization for destruction of Non-Conforming In-process product or Finished Product
Head-Quality Assurance/ Designee
Re-evaluation of Non conformance required/ not required
Re-evaluation of Non conformance:
Dated ………………….. by ………………………………………Department:……………………….
|Closure of Non Conformance:
Dated ………………….. by ………………………………………Department:……………………….
Product Name : Batch No. :
Manufacturing Date : Expiry Date: Batch Size:
Investigation Started on : Investigation completed on :
Suspected cause of product failure, if any:
Note: Investigation shall not restrict to this checklist, it can go beyond it.
|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
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.)
|iii. Check the environmental conditions in the quarantine area during storage of
|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
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
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 Open Fronted Containment Facility (OFCF) Records at the time of dispensing for the product batch:
i. Area purging records
ii. Line purging
iii. Cleaning records(of both OFCF, dispensing aids and vessels/ containers in which the materials have been dispensed
iv. Machine Log sheet
|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
iii. Pressure gauges of the Open Fronted Containment Facility
|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.||During the period of manufacture of the product|
|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 QA 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 purging 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 purging
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 /QC 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 QA, 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. 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 purging done before start of printing and packaging operations?
Check the line purging records of the packaging machine.
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 QA 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 QA:
iv. Does the product has any microbiological testing? If yes, date of release of batch
after microbiological analysis:
v. Date of dispatch of first consignment and quantity:
|41.||Check the Distribution Warehouse for:
iv. Storage condition
v. Environmental conditions
|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.
|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?|
|46.||Has the manufacturer informed Torque Pharmaceuticals regarding any major changes, if undertaken in process or specifications of the material being supplied by him?|
|Batch No.||Stage||Mfg date||Exp. date||Details of Non conformance||Implementation Status||NCR closed by date (Sign/Date)|