Handling of Investigation of Failure in Pharmaceutical Industry - A Review


  • Anupam Gulabdhar Pandey Oman Pharmaceutical Products Co. LLC., Raysut Industrial Estate, Salalah, Sultanate of Oman.


Investigation of Failure, Batch Failure, Failure, Manufacturing Process Investigation and Investigation


To conduct an effective failure investigation, we need to review in details to hit the root cause.
There are different areas to initiate with the investigation depending upon the nature of the failure and accordingly investigation is carried out.
Analytical: Confirmed Out of Specification.
Material: Qualification status of Vendors & review of test result of raw material/ packing material, Storage of Raw materials/ Packing materials & Deviation during Receipt/ Storage. Storage, Transportation and distribution of Finished Product.
Dispensing of Raw material/ Packing material: Line clearance procedures, Environmental condition and Deviation for/ during Dispensing. Review of Dispensing of Raw Material/ Packing material. Calibration status of Dispensing Balances and Qualification of the Personnel.
Manufacturing/ Packing: Line clearance procedures and Environmental condition for/ during manufacturing/ Packing. Review of Batch Manufacturing / Packing process and Process Validation of the product. Qualification, Calibration, Preventive maintenance and cleaning status of the equipments involved. Qualification/ training of the personnel involved in the Manufacturing/ Packing operation. Deviation/Non conformance during the Batch Manufacturing/ Packing.
Utilities and System: Review of the utilities and system involved in the manufacturing of the product. Deviation/Non conformance in the utilities and system.
Evaluation of Sample: Evaluation (Physical & Chemical) of Control samples and defective product received.
Quality System: Review of Deviation, Changes and stability test results associated with the product. Historical trend (Compliant/Recall/Failure).
Others: Impact on other batch/Product. Others, if any, which may cause the failure.


1. Title 21--Food and Drugs Chapter I--Food and Drug Administration Department of Health and Human services subchapter c--drugs: General - Part 211 current Good Manufacturing Practice for Finished Pharmaceuticals
2. (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/ cfcfr/CFRSearch.cfm?fr=211.198).
3. Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use - Part 1 Chapter 8: Complaints, Quality Defects and Product Recalls: Legal basis for publishing the detailed guidelines: Article 47 of Directive 2001/83/ EC on the Community code relating to medicinal products for human use and Article 51 of Directive 2001/82/EC on the Community code relating to veterinary medicinal products. This document provides guidance for the interpretation of the principles and guidelines of good manufacturing practice (GMP) for medicinal products as laid down in Directive 2003/94/ EC for medicinal products for human use and Directive 91/412/EEC for veterinary use.
4. (https://ec.europa.eu/health//sites/health/files/files/ eudralex/vol-4/2014-08_gmp_chap8.pdf)
5. Medicines & Healthcare products Regulatory Agency (MHRA): A Guide to Defective Medicinal Products - Reporting, Investigating and Recalling Suspected Defective Medicinal Products. A Guide for Patients, Healthcare Professionals, Manufacturers and Distributors. (https://www.gov.uk/government/http://uploads/system/uploads/attachment_data/ file/403210/A_guide_to_defective_medicines.pdf).
6. Therapeutic Good Administration (TGA) Guidelines: ICH Topic Q 7 Good Manufacturing Practice for Active Pharmaceutical Ingredients - NOTE FOR GUIDANCE ON GOOD MANUFACTURING PRACTICE FOR ACTIVE PHARMACEUTICAL INGREDIENTS (CPMP/ICH/4106/00). (http://www.ema.europa.eu/docs/en_GB/document_ library/Scientific_guideline/2009/09/WC500002825. pdf). Please note: Where European Union (EU) guidelines adopted in Australia include references to EU legislation (including EC Directives and Regulations), the requirements contained in the referenced EU legislation are not applicable to the evaluation of prescription medicines by the TGA. The Australian legislative requirements applying to prescription medicines are contained in the Therapeutic Goods Act 1989 and the Therapeutic Goods Regulations 1990, as well as in various legislative instruments such as Therapeutic Goods Orders, Notices and Determinations, see Legislation.
7. International Council for Harmonization (ICH) Guidance: ICH Q10 Pharmaceutical Quality System. (http://www.ich.org/fileadmin/Public_Web_Site/ ICH_Products/Guidelines/Quality/Q10/Presentation/ Q10_General_Presentation.pdf)
8. Pharmaceutical Inspection Co-operation Scheme (PIC/S) - GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS PART I - PE 009-13 (Part I) - 1 January 2017
9. (file:///C:/Documents%20and%20Settings/qauser4/ My%20Documents/Downloads/PE_009_13_GMP_ Guide_Part_I_Basic_Requirements_for_Medicinal_ Products_.pdf)
10. World Health Organization (WHO): WHO Expert Committee on Specifications for Pharmaceutical Preparations - WHO Technical Report Series, No. 908 - Thirty-seventh Report, (2003; 148 pages)
11. (http://apps.who.int/medicinedocs/en/d/ Js5517e/20.4.5.html#Js5517e.20.4.5)
12. Medicine Control Council (MCC) Guidelines: GUIDELINE FOR RECALL / WITHDRAWAL OF MEDICINES, MEDICAL DEVICES AND IVDs. 5.07_Recalls_Aug15_v4_for_ comment September 2015. (http://www.mccza.com/ documents/2f983a705.07_Recalls_Aug15_v4_for_ comment.pdf).
13. Saudi Food & Drug Authority - Guide to Good Manufacturing Practice for Medicinal Products - The basic concepts of Quality Assurance, Good Manufacturing Practice, Quality Control and Quality Risk Management are inter-related. They are described here in order to emphasize their relationships and their fundamental importance to the production and control of medicinal products.
14. HEALTH SCIENCES AUTHORITY–HEALTH PRODUCTS REGULATION GROUP: GUIDANCE NOTES ON PRODUCT QUALITY REVIEW - JANUARY 2013, REFERENCE PIC/S PE 009-10 (effective 01 January 2013). www.hsa.gov. sg (http://www.hsa.gov.sg/content/dam/HSA/HPRG/ Manufacturing_Importation_Distribution/Overview_ Framework_Policies/GUIDE-MQA-024-004.pdf)