PROCESS DEVELOPMENT, OPTIMIZATION AND VALIDATION OF MANUFACTURING PROCESS OF ALLOPURINOL
Objective: The objective of the present research work is to identify the critical parameters in the process that affect the quality of the finished product. The processs validation of the manufacturing process for Allopurinol tablet USP, 300 mg to be manufactured with change in manufacturing site and with increased batch size.
Methods: Prior to Scaling up to production, pilot batches were manufactured. Three consecutive commercial batches are to be produced using similar test equipment and in full compliance with cGMP and existing SOPs. Critical process parameters of the machine was set within operating range and was not exceeded upper and lower control limits during process operation. Equipment were operated within its assigned control limits, which shows upon scale up into new site, the specification for hardness did not meet requirements that had been set during development. There was no significant effect observed on thickness, friability, disintegration, dissolution, uniformity of dosage and were found within specification. Pre process batch was challenged by manufacturing product at upper and lower processing limits and circumstances which pose the greatest chance of process or product failure compared to ideal condition.
Results: Based on the data obtained from pre-process validation batch, operating ranges for compression force and machine speed had been established. Collected data shows robustness around these parameters and there is increased confidence that the process can be successfully scaled up under target conditions for these parameters.
Conclusion: From this study, it was concluded that process was optimized and gave a reproducible product that meet predetermined quality requirements and do so consistently and reliably.
2. Garston Smith H. Considerations for improving validation. J Validation Technol 2001;7:150–7.
3. Nash Robert A, Wacher Alfred H. Pharmaceutical process validation an International. 3rd edition. New York; 2003. p. 159, 198-229.
4. USA FDA, Drug process validation and drug application, Singapore; 2001.
5. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/QuestionsandAnswersonCurrentGoodManufacturingPracticescGMPforDrugs/ucm071836.htm. [Last accessed on 02 Oct 2020]
6. Raghunandanan R. Validation aspects of solid dosage forms pharma times; 2009. p. 41.
7. Guidelines on General Principles of Process Validation, Division of Manufacturing and Product Quality, CDER, FDA, Rockville, Maryland; 1987.
8. Guidance for Industry SUPAC-IR/MR: Immediate Release and Modified Release Solid Oral Dosage Forms U. S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER); 1999.
9. Shah Dhiron. Bureau of the census. Census of manufactures. U. S. Department of Commerce. 1995. SUPAC-IR and XPACs Industry Survey Report; 1997.
10. Quality Management Systems–Process Validation. edition 2. Available from: http://www.ghtf.org/sg3/sg3-final.html) [Last accessed on 02 Oct 2020]
11. Guidance for Industry, Scale-Up and Postapproval Changes, CDER, FDA; 1995.
12. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm [Last accessed on 02 Oct 2020]
13. Melkebeke VB, Vervaet C, Remon JP. Validation of a continuous granulation process using a twin-screw extruder. Int J Pharma 2008;356:224-30.
14. Jatto E, Okhamafe AO. An overview of pharmaceutical validation and process controls in drug development. Trop J Pharm Res 2002;1:115-22.
15. ICH harmonised tripartite guideline, “GMP guide for active pharmaceutical ingredients” Q8, current step 4 version, 10 Nov 2000.
16. Williams AC, Cooper VB, Thomasb L. ICH harmonised tripartite guideline, “GMP guide for active pharmaceutical ingredients” Q8, current step 4 version, 10 Nov 2000. Evaluation of physical drug form during granulation, tabletting and storage. Int J Pharm 2004;275:29-39.
17. United States pharmacopeia NF; 2011.
This work is licensed under a Creative Commons Attribution 4.0 International License.