1.0 1.

Purpose : This SOP defines the procedures for these production batches that require reprocessing.

2.0 2.1

Scope : Quality Improvement of a batch undertaken for any parameter by undertaking the same original process in full or in part as outlined in Master Process Instruction. Note: The batch which has undergone reprocessing will not be used for marketing in Export. Depending upon the nature of reprocessing, a joint discussion is held (if required) between Manufacturing, QA and Process Development Lab to determine 1. Reasons for failure and investigation there off. 2. Whether the batch is to be reprocessed to improve quality. 3. Whether stability studies will be required. 4. Whether any specific controls to be excised during reprocessing . 5. Reasons for reprocessing Based on the out come of this discussion if reprocessing is recommended then following procedure be adopted.

3.0 3.1

Definitions : Reprocessing: Introducing an intermediate or API, including one that does not conform to standards or specifications, back into the process and repeating a crystallization step or other appropriate chemical or physical manipulation steps that are part of the established manufacturing process. Continuation of a process step after an in-process control test has shown that the step is incomplete is considered to be part of the normal process, and not reprocessing. Responsibilities : Head Production Head Quality Assurance Head R&D Head safety : To identify the non-conforming product and inform about it to QA. : To investigate the cause of non-conformance and monitor the disposal procedure. : To carry out trials for reprocessing and to investigate and provide documents for rework procedure. : To monitor the disposal procedure as instructed by the R&D.

4.0 4.1 4.2 4.3 4.4

5.0 5.1

Activities / Procedure : Precautions : None

5.2

Any unusual observations made by production personnel during the manufacturing process are to be brought to the attention of Production Manager. These observations may include but not limited to following Colour pH Odour Any relevant observations. Any observation made by QC is brought to the attention of the QA Manager & Plant Manager. These observation may include but not limited to The condition listed in 5.2 above as well as in the following Description Assay Impurities Solubility Identification Clarity and colour of solution Acidity Heavy metals Light absorption Sulphated ash Loss on Drying (LOD) Before conducting reprocessing of a batch due to Quality failure, a detailed Investigation Report is

5.3

5.4

carried out to assist in taking suitable remedial actions for future batches. Based on the area of non-compliance and type of reprocessing, Production Manager initiates reprocessing by initiating Approval for Reprocessing. For the reprocessing of the failing batch or old batch, advice from Process Development Laboratory is to be taken as per the Master Manufacturing Procedure. For the reprocessing activities that involve physical operations like repacking, resifting, relabelling etc., advice from Process Development Laboratory is not required. Depending upon the operation(s) involved, for reprocessing few pages of current BMR shall be issued or a separate complete BMR shall be prepared as per Reprocessing Recommendation given by Process Development Laboratory. The batch record is issued to production after stamping REPROCESSED BATCH. Depending upon operations involved, during reprocessing In-process samples are tested in QC lab. Except for reprocessing that involves repacking and relabeling, after reprocessing fresh finished samples are withdrawn and tested. Final test report is issued for release of batch after verification of compliance as per product specification. The test report states that the batch is REPROCESSED. Batch number is assigned as per batch numbering SOP QAD/SOP/012. Adequate documents are prepared to describe the reasons, steps taken and final result. These document are the part of original Batch Production Record (BMR). Stability studies of the reprocessed batches will be undertaken based on the assessment of QA and Process Development Lab. The batches may be released after evaluation the quality of such batches

5.5

5.6 5.7 5.8 5.9 5.1 0 5.1 1

5.1 2

is similar to normal production batches. Disposal of non-conforming products:

5 The rejected material after reprocessing, which cannot be further reprocessed or reworked to meet the . specifications should be destroyed after taking prior approval from the Managing director. 1 3 . 1 5 The rejected material is disposed either by dissolving in water or appropriate solvent to drain into the . effluent treatment plant or to incinerate in presence of Safety HOD 1 3 . 2 5.1 3 Flow Chart : None

6.0 7.0 7.1 7.2 7.3 7.4 8.0 00

Abbreviation : None Reference Documents / Annexure ( Records/ Formats): Reference Documents : QAD/SOP/012 Batch Numbering System Annexure : QAD/SOP/029/A1 Approval for Reprocessing (QAD/SOP/029/F1/0) QAD/SOP/029/A2 Reprocessing Recommendation (QAD/SOP/029/F1/0) QAD/SOP/029/A3 Post Evaluation for Reprocessing Recommendation (QAD/SOP/029/F1/0) Revision History: Reason for Revision New Document

Rev No Effective Date