Standard Operating Procedure (SOP) for the Calculation of Yield and finalize the Limit at the different stages of drug product processing/manufacturing. This SOP is also applicable for Investigation of out of limit yield obtained during processing.
Calculation of Yield and finalize the Limit
1.0 OBJECTIVE :
-
- To lay down a procedure for fixation of yield and investigation of out of limits yield obtained at various stages of processing of a product.
2.0 SCOPE :
-
- This SOP shall be applicable for all Batch Records (Batch Manufacturing Record and Batch Packaging Record) for Calculation of Yield and finalize the Limit at the different processing stages.
-
- This SOP is also applicable for Investigation of out of limit yield obtained at pharmaceutical drug manufacturing plants.
3.0 RESPONSIBILITY- YIELD CALCULATION :
-
- Officer/ Executive Production: Evaluation of yields and Investigation of out of limit.
-
- Officer / Executive QA: Review of calculation data and Investigation of out of limit obtained.
-
- Head production: Review of Investigation of out of limit result obtained.
-
- Head, Q A: Compliance to SOP
-
- DEFINITION (S)
-
- Yield is a rationale of usable quantity obtained from a process to the actual starting quantity provided.
4.0 PROCEDURE FOR CALCULATION OF YIELD :
-
- % Yield (henceforth referred to as Yield) shall be evaluated at each stage were the quantifiable measure of a product is possible.
-
- However, yield shall be evaluated at different stages mentioned below but not limited to, depending on the nature of the process,
-
-
- End of granulation stage/ Dry Mixing
- Sizing / Compaction and Milling
- End of Blending
- Completion of compression/ filling
- End of coating*
- End of packing
- * Yield to be evaluated at each coating process for products where coating to be done in multiple stages (e.g. Seal coating, Polymer coating, Enteric coating, Polishing, Etc.)
-
-
-
Two types of yields shall be evaluated: % actual yield and reconciliation yield.
-
-
- The reconciliation shall be done for each stage.
-
- While undertaking reconciliation, Loss during the process, rejection, samples, and actual quantity shall be evaluated.
| Stage | Parameter | UOM |
| A | Actual batch size of the preceding stage | Kg |
| B | Actual weight of the stage | Kg |
| C | Samples for Analysis (QC + Inprocess) | Kg |
| D | Rejects | Kg |
| E | Loss during process | Kg |
-
- Reconciliation Yield = (B+C+D+E)/A x 100 =………….%
-
- When the packing of a product is done in multiple packs, the complete batch reconciliation shall be done after the completion of the last pack.
-
-
For the New Product :
-
-
- For a new product, the yield limit at each individual stage shall be provided as a tentative limit.
- If it is observed below tentative limits justification/ reasons to be provided in the concerned Batch Record.
-
- This is also applicable for existing / validated products when a major change in the manufacturing process is introduced.
-
- Assigning/ Resetting of limits shall be based on general process knowledge, batch size, sampling due to validation, etc.
-
- If any unwarranted low yield values are observed as that of tentative limits, adequate investigation to be done,
-
- However, the need of investigation depends on the nature of the process and decisions taken by stakeholders.
-
- Tentative limits shall be as per Table 1.
-
- However, limits may be made stringent or loose based on product nature / atypical process/ batch size/ packing types.
Table-1
For Tablets & Capsules (Up to 250,000 units) |
|
| Granulation/ Dry mixing | Not Less than 99.0 % |
| Sizing/ Compaction & Milling | Not Less than 98.5 % |
| Blending stage | Not Less than 98.0 % |
| Compression stage | Not Less than 97.5 % |
| Coating stage | Not Less than 97.0 % |
| Filling Stage | Not Less than 96.5 % |
| Inspection stage | Not Less than 96.0 % |
| Packing stage | Not Less than 95.5 % |
For Tablets & Capsules (> 250,000 units) |
|
| Granulation/ Dry mixing | Not Less than 99.5 % |
| Sizing/ Compaction & Milling | Not Less than 99.0 % |
| Blending stage | Not Less than 98.5 % |
| Compression stage | Not Less than 98.0 % |
| Coating stage | Not Less than 97.5 % |
| Filling Stage | Not Less than 97.0 % |
| Inspection stage | Not Less than 96.5 % |
| Packing stage | Not Less than 96.0 % |
Dry Powder injections |
|
| Blending | Not Less than 99.0 % |
| Filling | Not Less than 98.0 % |
| Packing | Not Less than 97.0 % |
Oral Dry Powder Suspension |
|
| Granulation/ Dry mixing | Not Less than 99.0 % |
| Sizing/ Compaction & Milling | Not Less than 98.5 % |
| Blending stage | Not Less than 98.0 % |
| Filling Stage | Not Less than 97.5 % |
| Packing stage | Not Less than 97.0 % |
-
- The yield for a product shall be fixed after completion of 10 manufacturing batches (excluding the validation batches) or at the time of completion of Product Quality Review (Refer SOP for APQR/PQR), whichever is early.
-
- In case it is fixed after completion of 10 batches, a certificate shall be attached to the Batch document (BMR or BPR) as per the template attached as Annexure-1.
- Where the yield is fixed, any out of limit obtained shall be investigated for possible reasons.
- The investigation shall be done on an unplanned deviation format (Refer SOP for Deviation).
- The head of the Department of Production shall provide a reason for the out of limit yield with corrective and preventive actions.
5.0 ABBREVIATION(S) :
-
- BMR: Batch Manufacturing Record
-
- BPR: Batch Packaging Record
Annexure – I: Yield certificate (template)
The yield of the …………………………………………………………………. (Product Name) has been fixed after completion of 10 consecutive batches ( ) / after completion of Product Quality Review ( ) (tick the appropriate)
The fixed limits are as below
|
Sr. No |
Stage | Previous Limit |
Revised Limit |
| 1. | |||
| 2. | |||
| 3. |
**********************************************END**********************************************
Pingback: Antimicrobial Efficacy Test - Guideline - Pharma Beginners