Open Access
Subscription Access
Open Access
Subscription Access
Investigation of Manufacturing Defects and Cgmp Lessons Learnt from Quality Issues in Pharmaceutical Sterile Preparations
Subscribe/Renew Journal
Any medicinal product introduced in the market ought to have the highest safety, quality, purity and efficacy as it is received by an ailing patient. Parenteral products are sterile pharmaceutical preparations that are injected, infused or implanted in the body. These products must maintain their quality and sterility as they are introduced directly into the bloodstream. Negligence associated with parenteral preparations can lead to severe or fatal adverse events. Although each country has its own regulatory body to keep a check on medication errors, defects keep occurring in pharmaceutical products. It should be the top priority of pharmaceutical companies to avoid these defects and related issues. This study focuses on three such real life defective parenteral products obtained from the hospital pharmacy. The probable root cause, remediation and clinical significance of the noted defect is also mentioned. These case studies can help pharmaceutical manufacturers minimize defects, quality issues to avoid product recalls and to achieve better therapeutic compliance.
Keywords
Parenteral preparations, Real life defects, Clinical significance, Quality, Sterility, Therapeutic compliance.
Subscription
Login to verify subscription
User
Font Size
Information
- Hemanth KG, et al. Pharmaceutical Defects: A critical review on defects of various dosage forms and regulatory impacts. Research Journal of Pharmacy and Technology. 2020 Sep;13(9):4505–8. doi: 10.5958/0974-360X.2020.00794.5
- Raul S, Padhy G, Mahapatra A, Charan S. An Overview of Concept of Pharmaceutical Validation. Research Journal of Pharmacy and Technology. 2014 Sep;7(9):1081-90. Available at: https://rjptonline.org/AbstractView.aspx?PID=2014-7-9-17
- Vyas S, Goyal A, Rath G. Introduction to Pharmaceutical Dosage Forms. In: Handbook of Pharmaceutical Dosage Forms. Vallabh Prakashan; 2011. pp. 71.
- Turco S, King R. Chapter 1- Introduction. In: Sterile Dosage Forms- Their Preparation and Clinical Application. 3rd ed. Lea & Febiger; 1987. pp. 7–8.
- Jones D. Parenteral Formulations. In: Pharmaceutics- Dosage Form and Design. Indian ed. Pharmaceutical Press; 2008. pp. 106–7.
- Kushwaha P. Parenteral Products. In: Handbook of Pharmaceutical Technology. Jaypee Brothers Medical Publishers; 2015. pp. 161.
- Frampton N, Dean D. Sterile products and the role of rubber components. In: Dean D, Evans E, Hall I, editors. Pharmaceutical Packaging Technology. 2nd ed. Taylor & Francis Group; 2000. pp. 345–62.
- Nebeker JR, Barach P, Samore MH. Clarifying Adverse Drug Events: A Clinician’s Guide to Terminology, Documentation, and Reporting. Annals of Internal Medicine. 2004 May;140(10):795–801. doi: 10.7326/0003-4819-140-10-200405180-00009
- Williams D. Medication errors. Journal of Royal College of Physicians of Edinburg. 2007 Jul;37(4):343–6.
- Samp JC, Touchette DR, Marinac JS, Kuo GM. Economic evaluation of the impact of medication errors reported by U.S. clinical pharmacists. Pharmacotherapy. 2014 Nov;34(4):350–7. doi: 10.1002/phar.1370
- Tax SS, Brown, Stephen; Chandrashekaran M. Customer Evaluations of for Service Complaint Experiences : Implications Relationship Marketing. Journal of Marketing. 2013;62(2):60–76. doi: 10.2307/1252161
- Vamshi, Kumar L, Muddukrishna B, Pai K. Market Complaints in Pharmaceuticals: A Brief Review on its Handling, Investigation and Reporting. Research Journal of Pharmacy and Technology. 2013 Jan;6(11):1314–6. Available at: https://www.scopus.com/inward/record.uri?eid=2-s2.0- 84903480516&partnerID=40&md5=b0a80dbf55077798266d43f6924215e2
- Rodriguez D. Six Sigma Methods to Reduce Defects and Variation - Invensis Learning [Internet]. 2020. Available at: https://www.invensislearning.com/blog/six-sigma-methods-to-reduce-defects-and-variation/
- Simplilearn. The Concept of Zero Defects in Quality Management [Updated] [Internet]. 2021 [cited 2021 Jun 15]. Available from: https://www.simplilearn.com/concept-of-zero-defects-quality-management-article
- Psarommatis F, May G, Dreyfus PA, Kiritsis D. Zero defect manufacturing: state-of-the-art review, shortcomings and future directions in research. International Journal of Production Research. 2019 Apr;58(1):1–17. doi: 10.1080/00207543.2019.1605228
- Kulkarni S, Panda A, Tiwari R. Pharmaceutical Process Validation: A Key Requirement for Quality Attribute. Research Journal of Pharmacy and Technology. 2014;7(1):74-7. Available at: https://rjptonline.org/AbstractView.aspx?PID=2014-7-1-7
- Forcinio H. Selecting Primary Packaging for Parenterals. Pharmaceutical Technology [Internet]. 2018;42(7):46–50. Available from: https://www.pharmtech.com/view/selecting-primary-packaging-parenterals
- Eakins M. Parenteral Products: Pharmacopeial Control of Containers, Storage and Distribution. American Pharmaceutical Review [Internet]. 2011;14(2). Available from: https://www.americanpharmaceuticalreview.com/Featured-Articles/37187-Parenteral-Products-Pharmacopeial-Control-of-Containers-Storage-and-Distribution/
- Avis K. Chapter 22- Sterile Products. In: The Theory and Practice of Industrial Pharmacy. Indian ed. CBS Publishers & Distributors Pvt Ltd; 2009. pp. 644–9.
- Dr Bettine Boltres. Primary packaging material for parenteral drugs [Internet]. 2015 [cited 2022 Jan 5]. Available from: https://www.expresspharma.in/primary-packaging-material-for-parenteral-drugs/
- Manoj. Review on: The Pharmaceutical Packaging [Internet]. 2011 [cited 2022 Jan 5]. Available from: https://www.pharmatutor.org/articles/the-pharmaceutical-packaging-article
- Benefits of Amber Glass Bottles in Packaging [Internet]. 2021 [cited 2022 Jan 5]. Available from: https://packagingoptionsdirect.com/benefits-of-amber-glass-bottles-in-packaging
- Tim Sandle. Closures for Pharmaceutical Preparations: A Review of Design and Test Considerations [Internet]. 2012 [cited 2022 Jan 5]. Available from: https://www.biopharminternational.com/view/closures-pharmaceutical-preparations-review-design-and-test-considerations
- Gopinath E, Bhadauria RS, Jain A. Pharmaceutical Product Recall: An Overview for Handling and Decision Making. Research Journal of Pharmacy and Technology. 2011;4(9):1333–9. doi: https://rjptonline.org/AbstractView.aspx?PID=2011-4-9-1
- Jabeen S, Sridhar S, Balamuralidhara V. Drug Recall Procedure in ASEAN Countries. Research Journal of Pharmacy and Technology. 2019;12(12):6041-8. doi: 10.5958/0974-360X.2019.01049.7
- CDSCO. Guidelines on Recall and Rapid Alert System for Drugs [Internet]. 2017 [cited 2022 Jan 5]. Available from: https://cdsco.gov.in/opencms/export/sites/CDSCO_WEB/Pdf-documents/biologicals/4GuidelineRecalRapidAlert.pdf
- FDA. Corrective and Preventive Actions (CAPA) [Internet]. 2014 [cited 2021 Jun 15]. Available from: https://www.fda.gov/corrective-and-preventive-actions-capa
- Vamshi TK, et al. Process Deviations in Pharmaceutical Industry: Various Types, Handling Procedure and Systems. Research Journal of Pharmacy and Technology. 2014 Jan;7(3):340–2. Available at: https://rjptonline.org/AbstractView.aspx?PID=2014-7-3-4
- Jain S, Jain R. Evolution of GMP in Pharmaceutical Industry. Research Journal of Pharmacy and Technology. 2017; 10(2) :601-6. doi: 10.5958/0974-360X.2017.00118.4
- Alexis Flaquiere and Jean Malthête. Qualification of Manual Visual Inspection Still Critical [Internet]. 2020 [cited 2022 Jan 5]. Available from: https://www.pda.org/pda-letter-portal/home/full-article/qualification-of-manual-visual-inspection-still-critical
- Janki Singh. Acceptable Quality Limit (AQL) Procedure & Chart [Internet]. 2020 [cited 2022 Jan 5]. Available from: https://guideline-sop.com/aql-acceptable-quality-limit-procedure-chart/
- Semi-automated visual inspection (SAVI) [Internet]. 2021 [cited 2022 Jan 5]. Available from: https://www.coriolis-pharma.com/analytical-services/particle-characterization/semi-automated-visual-inspection-savi
- All About Automated Visual Inspection Systems [Internet]. 2021 [cited 2022 Jan 5]. Available from: https://www.eaminc.com/blog/automated-visual-inspection-systems/
- Nayak A, et al. A Research on effective Management of Manufacturing defects to avoid Product Recalls: A Challenge to Pharmaceutical Industry. Research Journal of Pharmacy and Technology. 2019;12(12):6124–32. doi: 10.5958/0974-360X.2019.01064.3
- Hou Y, Wu G. Nutritionally essential amino acids. Advances in Nutrition. 2018 Nov;9(6):849–51. doi: 10.1093/advances/nmy054.
- Tawde SA. Particulate Matter in Injectables: Main cause for Recalls. Journal of Pharmacovigilance. 2015 Jan;03(01):1–2. doi: 10.4172/2329-6887.1000e128
- FDA. Quality System Regulation Labeling Requirements [Internet]. 2018 [cited 2021 Jun 15]. Available from: https://www.fda.gov/medical-devices/device-labeling/quality-system-regulation-labeling-requirements#specific
- Electronic Code of Federal Regulations (eCFR) Title 21: Part 201.18 Drugs; significance of control numbers. [Internet]. 2021 [cited 2021 Jun 15]. Available from: https://www.ecfr.gov/cgi-bin/retrieveECFR?gp=&SID=0d1aef6897c32d98264b24973e6234d3&mc=true&n=pt21.4.201&r=PART&ty=HTML#se21.4.201_118
- Turco S, King R. Appendix 2- Hazards Associated With Parenteral Therapy. In: Sterile Dosage Forms- Their Preparation and Clinical Application. 3rd ed. Lea & Febiger; 1987. pp. 363–92.
- Akers M. Chapter 41-Parenteral Preparations. In: Remington-The Science and Practice of Pharmacy Volume I. 21st ed. Lippincott Williams & Wilkins; 2005. pp. 818–9.
- CDSCO. Good Manufacturing Practices and Requirements of Premises, Plant and Equipment Pharmaceutical Products [Internet]. 2001. Available from: http://www.rajswasthya.nic.in/Drug Website 21.01.11/Revised Schedule M 4.pdf
- Turco S, King R. Chapter 4-Large Scale Preparation. In: Sterile Dosage Forms- Their Preparation and Clinical Application. 3rd ed. Lea & Febiger; 1987. pp. 39.
- DeLuca P, Knapp J. Chapter 3-Particulate Matter. In: Avis K, Lieberman H, Lachman L, editors. Pharmaceutical Dosage Forms: Parenteral Medications Volume 3. 2nd ed. Replika Press Pvt. Ltd, India; 2005. pp. 121–2.
- Levchuk J. Chapter 12- Parenteral Products in Hospital and Home Care Pharmacy Practice. In: Avis K, Lieberman H, Lachman L, editors. Pharmaceutical Dosage Forms: Parenteral Medications Volume 1. 2nd ed. Replika Press Pvt. Ltd, India; 2005. pp. 537.
- Luna C. Chapter 6- Personnel: The Key Factor in Clean Room Operations. In: Avis K, Lieberman H, Lachman L, editors. Pharmaceutical Dosage Forms: Parenteral Medications Volume 2. 2nd ed. Replika Press Pvt. Ltd, India; 2005. pp. 386–7.
- Levchuk J. Chapter 12- Parenteral Products in Hospital and Home Care Pharmacy Practice. In: Avis K, Lieberman H, Lachman L, editors. Pharmaceutical Dosage Forms: Parenteral Medications Volume 1. 2nd ed. Replika Press Pvt. Ltd, India; 2005. pp. 558–9.
- Electronic Code of Federal Regulations (eCFR) Title 21: Part 211.22 Responsibilities of quality control unit. [Internet]. 2021 [cited 2021 Jun 15]. Available from: https://www.ecfr.gov/cgi-bin/text-idx?SID=a90c1d262ff95c12594d76d6328548d4&mc=true&node=se21.4.211_122&rgn=div8
- Electronic Code of Federal Regulations (eCFR) Title 21: Part 211.42 Design and construction features. [Internet]. 2021 [cited 2021 Jun 15]. Available from: https://www.ecfr.gov/cgi-bin/text-idx? SID=7f1d0980849d17ec415b1b1bb3f8ebd2&mc=true&node=se21.4.211_142&rgn=div8
- Electronic Code of Federal Regulations (eCFR) Title 21: Part 211.46 Ventilation, air filtration, air heating and cooling. [Internet]. 2021 [cited 2021 Jun 15]. Available from: https://www.ecfr.gov/cgi-bin/text-idx?SID=7f1d0980849d17ec415b1b1bb3f8ebd2&mc=true&node=se21.4.211_146&rgn=div8
- FDA. FDA alerts health care professionals to voluntary nationwide recall of all sterile products from Coastal Meds [Internet]. 2018 [cited 2021 Jun 15]. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-health-care-professionals-voluntary-nationwide-recall-all-sterile-products-coastal-meds
- Martin LR, Williams SL, Haskard KB, DiMatteo MR. The challenge of patient adherence. Therapeutics and Clinical Risk Management. 2005 Sep;1(3):189–99.
- Glasby J. Regulatory Aspects of Pharmaceutical Packaging. In: Dean D, Evans E, Hall I, editors. Pharmaceutical Packaging Technology. Informa Healthcare, UK; 2010. pp. 94.
- Pai G, Hemanth, Thunga G. CS1: Small volume parenteral; Primary label having two generic names. In: Pharmaceutical Consumer Complaints-A guide to Academia and Pharmaceutical Industry. Manipal University Press; 2020. pp. 20–1.
- Levchuk J. Chapter 12- Parenteral Products in Hospital and Home Care Pharmacy Practice. In: Avis K, Lieberman H, Lachman L, editors. Pharmaceutical Dosage Forms: Parenteral Medications Volume 1. 2nd ed. Replika Press Pvt. Ltd, India; 2005. pp. 546–7.
- Pai G, Hemanth, Thunga G. CS13: Liquid Orals; Batch over-coding details missing on primary label. In: Pharmaceutical Consumer Complaints-A guide to Academia and Pharmaceutical Industry. Manipal University Press; 2020. pp. 40–1.
- Hanna S. Chapter 1- Quality assurance. In: Avis K, Lieberman H, Lachman L, editors. Pharmaceutical Dosage Forms: Parenteral Medications Volume 3. 2nd ed. Replika Press Pvt. Ltd, India; 2005. pp. 45–6.
- McConnell M. Chapter 115-Product Recalls and Withdrawals. In: Remington-The Science and Practice of Pharmacy Volume II. 21st ed. Lippincott Williams & Wilkins; 2005. pp. 2104.
- Jonathan A, et al. Medication errors: causes, prevention and reduction. British Journal of Haematology. 2002 Feb;116(2):255–65. doi: 10.1046/j.1365-2141.2002.03272.x
- Guchelaar HJ, Kalmeijer MD, Jansen MEP. Medication error due to ambiguous labelling of a commercial product. Pharmacy World and Science. 2004 Feb;26(1):10–1. doi: 10.1023/b:phar.0000013517.84814.58
- Hellier R, Kelly S. Medication errors and confusion over labelling. Journal of the Royal Society of Medicine. 2004 Oct;97(10):506. doi: 10.1258/jrsm.97.10.506-a
- Sanjay R, Narayan S, Manupriya C. In-Process Quality Control (IPQC): A Review. Indo American Journal of Pharmaceutical Research. 2017 Nov;7(10):707–11.
- Lachman L, Hanna S, Lin K. Chapter 27-Quality Control and Assurance. In: The Theory and Practice of Industrial Pharmacy. Indian ed. CBS Publishers & Distributors Pvt Ltd; 2009. pp. 829.
- Electronic Code of Federal Regulations (eCFR) Title 21: Part 211.25 Personnel qualifications. [Internet]. 2021 [cited 2021 Jun 15]. Available from: https://www.ecfr.gov/cgi-bin/text-idx?SID=7f1d0980849d17ec415b1b1bb3f8ebd2&mc=true&node=se21.4.211_125&rgn=div8
- Hemanth KG, et al. Solid dosage forms: A detailed research on non-conforming product quality. Indian Journal of Pharmaceutical Education and Research. 2020 Oct;54(3):S473–84. doi: 10.5530/ijper.54.3s.146
- Pai G, Muddukrishna, Hemanth, Thunga G. CS16: Capsules; Missing capsule and black particle on blister. In: Pharmaceutical Consumer Complaints-A guide to Academia and Pharmaceutical Industry. Manipal University Press; 2020. pp. 46–7.
Abstract Views: 103
PDF Views: 0