Out of Specification (OOS) test results have been a major concern during the manufacture of drugs for many decades. To avoid OOS in order to release the product, it has been found during audits and inspections that data or testing was manipulated (including compromising data integrity), product was re-tested repeatedly until a passing result was obtained or tests results were averaged using unapproved procedure to mask failing results. As most product specifications are based on statistical principles or methods, these methods were applied in an unethical manner to test a lot repeatedly until a passing result was obtained. The product was released on one passing result. Such practice has been known as "testing into compliance" and became a major issue following the 1993 lawsuit between the US Government and Barr Laboratories. Following historic judgement by Judge Alfred M. Wolin in 1993 on US versus Barr and FDA’s OOS Guidance issued in 2006 (Draft Guidance in 1998), handling OOS results and performing investigation into OOS by pharmaceutical companies receive close scrutiny during regulatory inspections. In this Seminar, historical aspects of OOS and understanding of the stigma associated with OOS will be presented in order to mitigate the risk for OOS. A thorough investigation procedure into OOS results following the FDA Guidance will be discussed with an aim to finding a root cause for the OOS. Challenges in Investigating OOS results for Microbiology testing will also be presented. Ways to avoid OOS risk will be discussed.
The CAPA system is an important QMS in the Pharmaceutical Industry and is a critical tool to achieve sustainable compliance through continuous improvement. A robust CAPA system, supported by a thorough investigation to find a root cause helps in improving manufacturing operations, the company and the business. As per ICH Q10 Guidelines, the pharmaceutical company should have a system for implementing CAPA resulting from the investigation of complaints, product rejections, non-conformances, recalls, deviations, audits, regulatory inspections and findings, and trends from process performance and product quality monitoring. This seminar will discuss the data of exceptions during manufacturing operations and performing investigations into these observations using a structured approach with the objective of determining the root cause. The level of effort, formality, and documentation of the investigation should be commensurate with the level of risk, in line with ICH Q9 guidelines. Ways to implement corrections, corrective actions and preventive actions and a follow-up to monitor effectiveness and sustainability of these procedures will be described.
Learning Objectives:
Upon completing this course the participants will understand:- Role and Responsibilities of Quality Control Unit with regard to assuring manufacture of quality products consistently and to achieving sustainable compliance during laboratory operations
- Laboratory Quality Management Systems and their role in QC operations
- Data of Exceptions - Deviations, Non-Conformances, Out of Specifications (OOS), Out of Trend (OOT), Out of Frequency (OOF)
- Managing Data of Exceptions
- Biological Deviations
- Regulations, History, Background and Importance of OOS
- Uncertainty of Methods & Re-testing
- Re-test and Investigative Testing during OOS investigation
- Issues with Testing into Compliance
- Reportable Results and Averaging of Data
- OOS investigations for Microbiological data
- OOS Investigation - Phase I Investigation, Phase II Investigation
- Re-testing, Re-Sampling, Outlier Tests
- Root Cause Analysis for Investigations from Deviations, Non-Conformances, OOS, OOT, OOF
- Correction, Corrective Actions and Preventive Actions
- Effectiveness and Sustainability of CAPA
Course Content
Course Provider
Rajesh Gupta,
Biologics Quality & Regulatory Consultants, LLCRajesh K. Gupta has a Ph.D. in microbiology and is the Principal Consultant at the Biologics Quality & Regulatory Consultants, LLC. He has more than 35 years' experience in the development, production, testing and regulation of biologics, working at both the regulatory agencies and the industry.
At FDA, CBER, he was a Deputy Director and the Lab Chief in the Division of Biological Standards and Quality Control, managing lot release of biological products, regulatory reviews of analytical methods in the biologics license applications (BLA), generation of reference standards and development of new methods.
In his previous jobs, he worked at the Biologics Consulting Group, Wyeth, Chiron, Massachusetts Public Health Labs and National Institutes of Health (NIH), in the USA and at National Institute of Immunology and Central Research Institute in India. His major accomplishments are in sterility assurance for biological products, adjuvants and delivery systems for vaccines, polysaccharide-protein conjugate vaccines, combination vaccines and development and validation of analytical methods. In these areas, he has published more than 100 papers in peer reviewed journals and books and has made numerous presentations at scientific and regulatory meetings.
Who Should Attend
- Pharmaceutical Industry
- Biotech Industry
- Managers and Scientists involved in Drug Development
- Analytical Development Managers and Scientists
- Quality Control Managers and Scientists
- Quality Assurance Staff for Informed Review of Data and for Managing and Providing Oversights on data integrity, Investigations, CAPA, etc.
- Senior Management and Corporate Team
