FINISHED PRODUCT SPECIFICATION

Transcription

1 Product : Triptorelin Product / Item No : Specification : PPLI/FPS/TP Synonym : Not Applicable Abbreviation : Not Applicable Molecular weight : Effective Date : APPROVALS Prepared by : Bhagwan Shinde, Executive QC Date: Reviewed by : Sharangi Vaiude, Asst. Manager, Microbiology Date: QC Approval : Ravindra Mohite, Asst. Manager, QC Date: Production Approval : Atul Harshe, Manager Production Date: QA Approval : Rajkumar Mirajgave, Manager Quality Unit Date: SEQUENCE: pglu-his-trp-ser-tyr-dtrp-leu-arg-pro-gly-nh 2 TEST SPECIFICATION METHOD 1 Appearance White to off-white homogeneous powder SOP-IQC-101# 2 Clarity (10 mg/ml Solution in Milli-Q water or Equivalent) Clear SOP-IQC Color (10 mg/ml Solution in Milli-Q water or Equivalent) 4 Solubility Colorless or < Y 7 Water, acetic acid: Very soluble Ethanol: Sparingly soluble Hexane: Practically insoluble SOP-IQC-155 SOP-IQC-106 Page 1 of (4)

2 Product : Triptorelin Specification No: PPLI/FPS/TP TEST SPECIFICATION METHOD 5 IDENTIFICATION (by Mass Spectral Analysis) Monoisotopic Mass: ± 0.4 m.u. SOP-IQC-111* 6 IDENTIFICATION The main peak co-elutes with reference SOP-IQC-156# 7 PURITY Related substances [D-Ser] 4 -Triptorelin 0.5% [D-Tyr] 5 -Triptorelin 0.5% Sum of [DesGly]-Triptorelin and [D-Leu] 7 -Triptorelin 0.5% Sum of [D-His] 2 -Triptorelin and [D-Glu]-Triptorelin 0.5% Triptorelin-OH 0.5% [EndoGly]-Triptorelin 0.5% Any unspecified impurities 0.5% Sum of all impurities 1.5% SOP-IQC-156# 8 Water content by Karl Fisher 7.0 % SOP-IQC-105# 9 Acetic Acid Content % SOP-IQC Residual Trifluoroacetic acid 0.1 % SOP-IQC Specific Optical Rotation [ ] D ~ 20 (c= 1,1% HOAc) -67 to -77 (With reference to anhydrous and acetic acid free substance) SOP-IQC Residual organic solvent Acetonitrile 410 ppm Tert-butyl-methyl-ether 5000 ppm Heptane 5000 ppm SOP-IQC Microbiological Tests Total aerobic microbial count TAMC Total Yeast and Mould count TYMC 100 CFU/0.1g 10 CFU/0.1g SOP-IQC-711 Page 2 of (4)

3 Product : Triptorelin Specification No: PPLI/FPS/TP TEST SPECIFICATION METHOD 14 Bacterial Endotoxins 10 EU/mg SOP-IQC Triptorelin Content, Note the results SOP-IQC Mass Balance 95% - 105% (NPC/100-AcOH-H2O-Sum of impurities)*100 * Analysis shall be performed at Contract Laboratory. #Tests to be performed when retesting. SOP-IQC-132 Sample size for Analysis QC Sample size for Micro Sample size for retention QC Sample size for retention Micro References: Approx. 750 mg Approx. 220 mg Approx mg Approx. 2 X 220 mg Retest Period: 12 months Storage condition -20 C ± 5 C Triptorelin Specification for registration batches received from Malmo with article number Revision History: Revision : 0.0 Change Control Number CC Effective Date 25/10/2013 Reason for Revision New Document Revision : 1.0 Change Control Number CC Effective Date 06/03/2014 Reason for Revision Revised SOR limit from between -66.0º & º to -67º & - 77º, minor editorial changes. Page 3 of (4)

4 Product : Triptorelin Specification No: PPLI/FPS/TP Revision : 1.1 Change Control Number CC Effective Date Reason for Revision 1. To add EndoGly-Triptorelin 0.5% and replacing [D-Leu] 7 - Triptorelin by Sum of [DesGly-Triptorelin] and [D-Leu] 7 - Triptorelin 0.5%. 2. To add Sum of [D-His] 2 -Triptorelin and [D-pGlu]-Triptorelin 0.5% by eliminating [D-His] 2 -Triptorelin as a single impurity. 3. Net peptide content determined by AAA to be replaced by with results to be noted from 80%. 4. To eliminate N, N-Dimethyformamide; limit: 880 ppm, Diisopropylethylamine; Limit: report results and 2- propanol; Limit: 5000 ppm and add Heptane; limit 5000 ppm. Annexure-I for data monitoring. Page 4 of (4)

5 Product : Triptorelin Specification No: PPLI/FPS/TP ANNEXURE I Following tests shall be performed for registration and Process validation batches & for data compilation purpose and not for release. TEST SPECIFICATION METHOD 1 Sequence by MS-MS Confirms expected sequence SOP-IQC-111* 2 Chiral purity Report values GC* 3 Elemental impurities Report results ICP-MS* 4 IDENTIFICATION (by UV Spectroscopy) ^max =280 nm with a shoulder at 287nm ^min =247 nm A 0.005% 1cm at 280nm=0.427 to SOP-IQC-133 (With reference to anhydrous and acetic acid free substance) 5 Purity Unrelated substances Any unspecified impurity 0.15% LC-MS* * Analysis shall be performed at Contract Laboratory. Page 1 of (1)

6 Product: Triptorelin ANALYTICAL REPORT Page 1 of 2 Product /Item PPL Lot Q.C. AR Retest Date Specification Number: PPLI/FPS/TP Appearance Test Specification Test Method Result White to off-white homogeneous powder SOP-IQC-101# 2 Clarity (10 mg/ml Solution in Milli-Q water or Equivalent) Clear SOP-IQC Color (10 mg/ml Solution in Milli-Q water or Equivalent) 4 Solubility 5 IDENTIFICATION (by Mass Spectral Analysis) Colorless or < Y 7 Water, acetic acid: Very soluble Ethanol: Sparingly soluble Hexane: Practically insoluble SOP-IQC-155 SOP-IQC-106 Monoisotopic Mass: ± 0.4 m.u. SOP-IQC-111* 6 IDENTIFICATION The main peak co-elutes with reference SOP-IQC-156# 7 PURITY Related substances Sum of impurities by Any single impurity by [D-Ser] 4 -Triptorelin 0.5% [D-Tyr] 5 -Triptorelin 0.5% Sum of [DesGly]-Triptorelin and [D- Leu] 7 -Triptorelin 0.5% Sum of [D-His] 2 -Triptorelin and [D- Glu]-Triptorelin 0.5% Triptorelin-OH 0.5% [EndoGly]-Triptorelin 0.5% Any unspecified impurities 0.5% Sum of all impurities 1.5% SOP-IQC-156# 8 Water content by Karl Fisher 7.0 % SOP-IQC-105# 9 Acetic Acid Content % SOP-IQC Residual Trifluoroacetic acid 0.1 % SOP-IQC Specific Optical Rotation [ ] D ~20 (c= 1,1% HOAc) -67 to -77 (With reference to anhydrous and acetic acid free substance) SOP-IQC-107

7 ANALYTICAL REPORT Page 2 of 2 Product: Triptorelin Q.C. AR Test Specification Test Method Result 12 Residual organic solvent 13 Microbiological Tests Total aerobic microbial count TAMC Total Yeast and Mould count TYMC Acetonitrile 410 ppm Tert-butyl-methyl-ether 5000 ppm Heptane 5000 ppm 100 CFU/0.1g 10 CFU/0.1g SOP-IQC-146 SOP-IQC Bacterial Endotoxins 10 EU/mg SOP-IQC Triptorelin Content, Note the results SOP-IQC Mass Balance * Analysis performed by Contract Laboratory # Tests to be performed when retesting. 95% - 105% (NPC/100-AcOH-H 2O-Sum of impurities)*100 SOP-IQC-132 Conclusion: Complies/Does not comply as per above Specification Signature Prepared by Checked by Approved by Date

8 ANALYTICAL REPORT FOR ANNEXURE I Page 1 of 1 Product: Triptorelin Q.C. Reference TEST SPECIFICATION METHOD Result 1 Sequence by MS-MS Confirms expected sequence SOP-IQC-111* 2 Chiral purity Report values GC* 3 Elemental impurities Report results ICP-MS* 4 IDENTIFICATION (by UV Spectroscopy) 5 Purity Unrelated substances ^max =280 nm with a shoulder at 287nm ^min =247 nm A 0.005% 1cm at 280nm=0.427 to (With reference to anhydrous and acetic acid free substance) Any unspecified impurity 0.15% SOP-IQC-133 LC-MS* Conclusion: Tests performed for registration and Process validation batches & for data compilation purpose and not for release. Signature Prepared by Checked by Approved by Date