STANDARD OPERATING PROCEDURE MANUFACTURING INVESTIGATION REPORTING SYSTEM.

STANDARD OPERATING PROCEDURE

SUBJECT: MANUFACTURING INVESTIGATION REPORTING SYSTEM.

DEPARTMENT           : QA SOP NO.                      : Page No                       : Effective Date             : Next Review                : SOP REVISION            :

     

1.0       OBJECTIVE:

The purpose of this procedure is to identify the events (variances, discrepancies, unplanned deviations) in manufacturing, packing, distribution and handling of Active Pharmaceutical Ingredients that are subject to investigation, to describe the procedure and timelines for investigations, it’s reporting to management, tracking  &  trending  of  investigations, and documentation.

2.0       POLICY:

2.1       This procedure is applicable to manufacturing, testing and warehousing operations.

2.2       This procedure shall be followed if any of the following events is observed:

2.2.1    Damaged or unlabelled or incorrect receipt of raw materials,

      

2.2.2    Improper sampling techniques,

      

2.2.3    Incorrect dispersal of R.M/P.M

     

2.2.4    Use of unapproved or incorrect production material,

      

2.2.5    Use of wrong version or unapproved document,

      

2.2.6    Equipment / instrument not in calibrated state or out of tolerance   or status stickers missing,

      

2.2.7    Violation / Deviations from established, validated procedure, process parameters or system during                   manufacturing or testing.

2.2.8    Environmental parameters exceeding action limits,

2.2.9    Fortification,

2.2.10  In-process failure,

2.2.11  Any equipment, instrument or procedure (system) failure that may or may not create hazard to the product quality and may or may not result in quality problem,

2.2.12  Any human error / failure that may or may not result in any type of quality problem, Spillage, drain or loss of raw / packaging material,                                                                                            

  

2.2.13  Reprocessing in manufacturing, is permissible for tablets, liquid orals etc. No reprocessing is allowed for Creams, Lotions & Ointments.

2.2.14  Laboratory out of specification when the test results indicate the problem in manufacturing,

2.2.15  Testing not performed within established timeframe or not performed at all,

2.2.16  Product complaint and recalls,

2.2.17  Contamination / Cross Contamination,

2.2.18  Calculation errors, missing reading or entries,

2.2.19  Incorrect dispatch of finished goods,

2.2.20  Reduction in approved expiration etc….

2.2.21  Any event that is not listed above but is vital for the cost and quality of the product shall be considered.

2.3       KEY ROLES AND RESPONSIBILITIES:

2.3.1    All personnel      :    Identify and communicate reportable event.

2.3.2    The Section In charge: Take immediate actions, Initiating investigation form, taking necessary corrective actions and preventive measures, follow up for the action getting authorization, attaching a Copy of completed investigation form to BMR and submitting original form to QA.

2.3.3    Head of the      : Completing the Investigation procedure within Department stipulated time.

2.3.4    Manager, Q.A. : Assigning numbers to investigation                

                                                                                                                                   

2.3.5    Investigation team        : Conduct thorough and timely investigation involving concerned personnel

           

2.3.6    Quality  Council: Ensure  effectiveness  of  corrective  actions  and measure  the  performance  of  the  investigation process.

2.4       DEFINITIONS

Assignable Cause - A documented and scientifically justified determination made by the laboratory that the discrepant result is due to laboratory error. This is detailed in a Laboratory Investigation Report. [Note: Assignable cause is congruent with the term “determinate cause.” The absence of an assignable cause is known as an “indeterminate cause.”]

Batch Failure – A determination of unacceptability of a critical quality attribute based upon at least one (1) confirmed out-of-specification laboratory result that should result in rejection of the batch.

Manufacturing Investigation – A formal process employed to investigate and recommend appropriate corrective actions stemming from a confirmed laboratory out-of-specification result (related to production or support services) for which no laboratory assignable cause has been identified or conclusively proven. A cross-functional team composed of departmental representatives from Quality; Manufacturing etc will conduct an investigation.

Manufacturing Investigation Report (MIR) - The detailed, centrally archived document that constitutes a compilation of the documents generated during the manufacturing related investigation process, i.e., Laboratory Investigation Report and Manufacturing Investigation findings.

Manufacturing Discrepancy - Any outcome of a procedure or an occurrence during the performance of a production operation differing from the normal or expected.

Out-of-Specification (OOS) Result - All results that fall outside the specifications or acceptance criteria established in new drug applications, official compendia or by the manufacturer.

Planned Deviation: A deviation that is known to all functionary departments before the issue of batch manufacturing record. (E.g: Non availability of secondary packing materials like literature, labels etc. before the start of manufacturing).

Unplanned Deviation: A deviation that happens during the process of Manufacturing & Packing due to sudden breakdown of equipment etc. (E.g. Break down of online coding machine and coding done off line).

           

ABBREVIATIONS

MIR     -           Manufacturing Investigation Report

            HOD   -           Head of the Department

            GMP   -           Good Manufacturing Practices

QA      -           Quality Assurance

            IMR    -           Integrated Management Report

             OOS    -           Out of Specification

3.0       PROCEDURE:

3.1       The area in-charge shall report the incident verbally to the Department Head who in turn shall report the same to the Q.A. Head and Facility Head within one business day.

3.2       Q.A. Manager shall allot the investigation form number as follows upon receipt of the notification. 

Constitution of the No :           Year / Serial Number

The year shall be 03, 04, 05 for the years 2003, 2004, 2005, etc…

The Sr. No. shall be 01 to n for a year. Shall start from 01 from next January.

3.3       The Management representative of the area where any of the event as explained in the scope is observed shall complete the Part I & II of the manufacturing investigation report form (Hereinafter referred as MIR form, attached to this SOP) within three working days and submit it to the department Head for further action.

3.4       The Section In-charge shall withhold and quarantine (isolate) the affected lot / batch until the final batch disposition is decided / suggested by the investigation team.

3.5       A team of Department Head (Team Leader), Section In-charge of the area (who had initiated the investigation form) and a Q.A. representative shall conduct / complete the investigations within 30 days of the occurrence of the event.

3.6       The Department Head shall decide upon the investigation date (planning) and additional decision criteria, if any, in consultation / concurrence with Q.A. and other team members including the principal company representative.

3.7       The Department Head, from time to time, shall report verbally to the Management about the progress of the investigation if required.

3.8       The Section In-charge (who had initiated the investigation form) shall take the corrective actions and preventive measures as recommended in the MIR form by the specified date.

3.9       The Section In-charge shall get approval of the Q.A. Manager and facility Head.

3.10     Q.A. Manager shall indicate his views in the of investigation form about various requirements.

3.11     The Q.A. Department shall submit a copy of duly authorized MIR form for Q.A. concurrence if it is indicated on the form. The final lot disposition shall be done upon receipt of Principal concurrence

3.12     The Section In-charge shall intimate to Q.A. Executive and seek his acknowledgement on the MIR form when MIR review is required before batch release.

3.13     The Section In-charge shall complete / close out the investigation process by completing the MIR form,  attach  a  copy  of  duly  completed  &  approved  MIR  to  batch  manufacturing / packing  records and submit the original investigation form to Q.A.

The original Investigation form shall be maintained in Q.A.

3.14     Investigation procedure and completed Investigation Forms are confidential Company documents. Photocopying and / or giving it to outside personnel / agencies is not permitted except approved by Q.A.

3.15     GUIDELINES FOR VARIOUS ASPECTS OF INVESTIGATIONS:        

3.15.1              LOT DISPOSITION:   

3.15.1.1           If the quality of the product is suspected to be adversely affected OR accessed as adversely affected, the affected batch or part of the batch shall be destroyed as per relevant procedure.

3.15.1.2           If the quality of the product may not be adversely affected by reprocessing or repacking, it can be done so as per relevant procedure.

3.15.1.3                       Follow the recall procedure for goods recalled or returned from market.

3.15.1.4           The Q.A. shall be informed by Section In-charge / Department Head about the incident before the final release of the affected batch / lot.

                                                           

3.15.2              IMPACT OF THE PROBLEM:

3.15.2.1           If the problem has potential to impact other lots, products, validated processes or systems negatively, it can be indicated in the investigation form.

3.15.2.2                The Head of Department shall suggest / take necessary corrective actions/ preventive measures.

3.15.2.3                       He shall keep necessary documentation for the actions.

3.15.3              NO ASSIGNABLE CAUSE:

3.15.3.1           The Head of Department shall extend the investigations to the previous and / or next batches, processes, products or systems if the investigation is concluded with ‘No Assignable Cause.’

3.15.3.2           The same shall be indicated in the investigation form.

3.15.3.3           The Section In-charge shall complete MIR form.

3.15.4              PRINCIPAL Q.A. CONCURRENCE:

3.15.4.1                       Following situations require principal Q.A. concurrence before final disposition.

3.15.4.2                       Market recalls,

3.15.4.3                       Product mix ups,

3.15.4.4                       Suspected contaminations,

3.15.4.5                       Yield alert,

3.15.4.6                       Reduction in approved expiration,

3.15.4.7                       Events that has potentially affected the quality, safety or efficacy of the product,

3.15.4.8                      Batches failing in release testing,

3.15.4.9           When MIRs require Q.A. concurrence, a copy of duly completed locally approved MIR shall be submitted to Q.A. 

 

3.15.4.10         If Q.A. concurs with batch / lot disposition recommendations, they shall return approved copy to the site Q.A. head. The affected batch / lot shall be disposed upon concurrence.

3.15.4.11         If Q.A. do not concurs with the MIR recommendations, additional information / Executive summary shall be provided or amended MIR shall be submitted.

3.15.4.12         Q.A. shall provide their final decision to concur or not.

3.15.5              METRICS:

3.15.5.1           All the departments shall maintain records as suggested by IMR co- coordinators and report the metrics on regular basis.          

3.15.5.2           The Quality Council shall review the metrics to identify and recommend Corrective actions and preventive measures and monitor the effectiveness of the actions.

4.0       FREQUENCY:  As and when required.

5.0       RESPONSIBILITY:  GM-QA, Manager-Production.

6.0       REVIEW GUIDE: Manufacturing investigation report.

7.0       ANNEXURE: 1. Manufacturing Investigation Report Form (MIR Form)

8.0       SOPs DISTRIBUTION:

            This SOP shall be distributed to following Departments:

Name of the Department	Master Copy	Circulatory Copy
QA/QC	√	√
Production	x	√
Warehouse	x	x
General	x	x
Maintenance	x	x