0 Purpose:        To provide instructions for batch deviation handling. The purpose and objective of this SOP is to lay down the steps for dealing with batch deviations, re-processing and rejections which occur due to various reasons as a part of the manufacturing process for API. It includes immediate implementation of necessary measures, investigations of the cause of problem, failure analysis, correction of the problem and appropriate measures to prevent recurrence.

2.0  Objective:      To provide a documented procedure of batch deviation handling. The objective

                               of this  SOP is to describe how deviations and failures during the manufacture of a    drug  substance or drug product will be investigated and documented.

3.0    Scope:           This procedure is applicable for batch deviation handling.

4.0  Responsibility:

·        Primary: Officer – QA / Officer – Production

·        Secondary: Production In-change

5.0  Procedure:

·        Definition

Ø       A batch deviation is any event during the course of manufacture or testing, which prevents it from being processed and / or released in the routine way. This entails a proper investigation as regards the reason for the failure, the corrective actions being implemented and the preventive mechanism that will prevent a recurrence of the same or a similar incidence. Some examples of a Batch Deviation are given in checklist.

Ø      The term batch deviation is defined as the unplanned non-compliance with procedures and specification, control tests and SOPs that are laid down in writing and may or may not affect the quality of the product.

Ø      A failure investigation is initiated when Quality Control results fail to comply with established specification. A failure is defined as any unplanned incident that has an impact on the acceptability status of a product during manufacture.

·        Requirements: -

Ø      Batch Deviation: - The investigation, resulting out of specification batch deviation or batch difficulty as and when it is observed, must be followed and the form mentioned below must be filled and processed.

• Batch deviation observed by: - Production / Q.C / Q. A.

• Describe the deviation in brief with date and time of observation.

• Mention the Batch / Batches of the involved product.

• Corrective action if taken immediately.

• Reason for probable causes for deviation.

o       Signature & Date by QC___________ Production __________

Ø      Forward the filled form to QA

·        QA investigates in to the causes of the failure evaluates the immediate and following corrective actions and recommends whether the affected batch / batches can be released or reprocessed or rejected, whether stability testing or any other additional testing is warranted must be commented by QA. If required preceding and succeeding batches may also need to be evaluated. The final responsibility of the batch to be released or rejected lies with the QA In-charge. Comments on corrective action / preventive action to avoid a recurrence must be jointly agreed and made by the QA / QC and production departments.

·        The entire investigation and rationale for the final decision is documented, signed and dated and maintained along with the Batch Record. A copy to be forwarded to QA for records. All Batch Deviation should be tracked and reported on a biannual basis and a summary report is forwarded to The Chairman, Head of Production and Head of QA / QC.

·        Raw material failures are not included in the purview of this SOP. However, if a raw material is accepted for production and is the cause of the failure, then it must be included in this batch deviation system.

·        QA must later check if preventive action has been implemented.

·        Checklist:

Ø      General

o       All rejected batches

o       All batches that need rework or reprocessing.

o       All batches that can only be partially released.

o       All batches with yields that are outside the established acceptable range, e.g. excessive product loss due to equipment malfunction.

o       All significant deviations from written procedures (Batch Manufacturing Records, Testing Procedures, Standard Operating Procedures)

o       Unplanned changes to the production / manufacturing process.

o       Any observation outside routine experience indicating at least a potential quality problem.

o       Potential mix up found at the site.

Ø      Testing: Out of specification results of Raw Material, Intermediates, and Finished Products

o       Any re-testing due to unexpected results during the first testing.

o       Use of testing equipment

o       That was not successfully calibrated or

o       Calibration expired before use of the equipment

o       Stability test failures.

Ø      Bulk Drug: -

o       Check weighs errors of active components which result in potentially low/high potency / assay product.

o       Use of non-released and / or rejected raw materials

o       Out of sequence addition of raw material.

o       Weighing process error, e.g. one batch receives one component twice.

o       Maximum processing / storage periods are exceeded.

o       In process controls not performed as required (including wrong time / wrong amount)

Ø      Contamination

o       Fibers / papers / plastic pieces found from raw material or in – process compound.

o       Nuts / bolts / hard objects found or going through processing equipment and came in contact or mixed with product causing metal contamination.

o       Insect or insect parts ( dead or alive ) found in product or during processing.

o       Discolored material found in raw material while processing dispute the former testing and release of the raw material.

o       Cross product contamination due to inadequate cleaning ( e.g. carry – over of product residue / cleaning solution to subsequent product due to failure in equipment cleaning)

o       Product or in-process components from one lot mixed with another lot due to potential loss of each lot identity.

o       Damaged material at receipt or sampling.

Ø      Equipment failures

o       Equipment failure causing batch to run significantly outside validated parameter range.

Ø      Utilities failures

o       Problems with air / water / steam supply that disrupt manufacturing cycles.

o       Energy breakdown with process interruptions not controlled during the interruption.

6.0  Reference Document:

·             Batch Deviation Form

7.0  Abbreviations:

·             QA   = Quality Assurance department

·             SOP = Standard Operating Procedure

·             QC = Quality Control

8.0  Copies to Distribution Sites :

·             QA

·             Production

BATCH DEVIATION FORM

    To,

    QA Manager,

    Name of the Product                 : ______________________________

    Observed By                             : Dept.:_____________Name:_______

    Description of the Deviation      : ______________________________

    Affected Batch / Batches           : ______________________________

    Mfg. / Exp. Date                        : ______________________________

    Date & time of Occurrence /     : ______________________________

    Detection of the Deviation

    Corrective action if taken          : ______________________________

    Immediately

    Reason of Deviation                 : ______________________________

    Sign / Date                               Quality Control                 Production

    CORRECTIVE ACTIONS / PREVENTIVE ACTIONS :-

    Signature / Date

    Quality Control                  Production

    Final Statement: - Release / Rejected by QC / Q.A.

    Name / Sign. / Date

    QC / Q.A.