White Paper. Risk Management in Environmental Monitoring: Should you be spotting it sooner?

Transcription

1 White Paper Risk Management in Environmental Monitoring: Should you be spotting it sooner?

2 Executive Overview Quality Risk Management is a comparatively new approach in the pharmaceutical manufacturing industry. Historically, the pharmaceutical manufacturing industry has focused on regulatory compliance as the means to achieve product quality; the industry has now shifted to include a more robust and holistic process incorporating risk-based quality management. Starting with the publication of Pharmaceutical cgmps for the 21st Century A Risk-Based Approach, in August 2002, several international publications have followed in fashion, including, ICH Q9 Quality Risk Management, and the Parenteral Drug Association (PDA) Technical Report No. 44 on Quality Risk Management for Aseptic Processes, and ICH Q10 Pharmaceutical Quality System. The trend over the last decade has moved towards Quality Risk Management, this is apparent as the strategy is being incorporated into more and more organizations procedures. A strategically planned, and effectively executed, environmental monitoring program, delivers enhanced assurance of sterility for aseptically produced products. Over the past decade, environmental monitoring has evolved into a more complex process switching from a grid based approach, sampling in cleanrooms section by section, to the more recent approach, which emphasizes risk assessment, and the application of risk assessment tools, to define the most representative locations, and methods, for environmental monitoring sampling. Environmental Monitoring is an important process through which the efficiency of contamination control procedures can be measured, and the possible threats to the pureness of products being produced can be identified. The outcome of environmental monitoring needs to be part of the equation when assessing whether a batch can be released. There are many potential uses for Quality Risk Management in the pharmaceutical industry: this white paper focuses on its application in cleanroom control, specifically relating to Environmental Monitoring and the interpretation of the data generated from monitoring, by using examples of the risks associated with monitoring, and the mitigation of those risks. Risk Management in Environmental Monitoring: Should you be spotting it sooner? 2

3 Business Challenge What are the risks involved in Environmental Monitoring? How can we spot it sooner? How does a risk based approach apply to an automated Environmental Monitoring program? Risks in Environmental Monitoring begin with the sheer amount of data generated from sampling, and the required evaluation of the data as the basis for determining those sampling sites. Risks continue throughout the process making it necessary to include trending for process control, pattern recognition, and root cause analysis. These risk factors are compounded by time; data trending should be done in real-time, and being able to trend it quickly and effectively by collecting, organizing, and analyzing your data in a meaningful way will substantially reduce risk. RISK 1: INEFFECTIVE ANALYSIS DUE TO HIGH VOLUME OF DATA Environmental Monitoring produces large amounts of data; each sample taken must track everything from lot of Media used, to incubators, and personnel, with which the sample has come in contact. The table below shows the fields which are typically captured for each and every viable sample taken; this is not a complete list as various organizations will track other criteria as well. Environmental Monitoring Data Fields Sample Type Taken By Media Type Equipment ID Room Handled By Media Lot No. Calibration Date Location Read By Equipment Exposure Time Operator (Gowning Lot Number Microorganism Incubator (20-22 C ) Monitoring) identification Date Test Taken Equipment Genus Temp Date Test Entered Media Species Time / Unit Test Disposition Sample Start Time Strain Calibration Date Location Description Sample End Time Gram Stain Incubator (30-32 C ) Group Shift Reference Temp Room Classification Comments Micro Comment Time / Unit Room Status ID Code Exposure Calibration Date In the case of fixed, continuous monitoring, non-viable samples, the volume of results for the 5.0µ and 0.5µ can be upwards of 20,000 data points per day. Tracking this data is a must when effectively managing an Environmental Monitoring Program; the critical data is the data you do not have when conducting an investigation into a failure. Applying such measures requires adaption to large amounts of data entry in an expedited manner; otherwise known as rapid data entry. Further, the system should be a truly paperless automated system. Rapid data entry grid-based screens are the most flexible and efficient way to enter data in batches, or copy it across different criteria and different samples. Adding in Barcoding/RFID technology can provide additional automation, in addition to connectivity of instruments for direct data transfer. Finally, system availability would be provided on tablets and notebooks with touchscreen interfaces. Risk Management in Environmental Monitoring: Should you be spotting it sooner? 3

4 RISK 2: LACK OF PATTERN RECOGNITION DUE TO POOR TRENDING METHODS Remediation involves having a system in place with robust analysis capabilities, real-time trending and correlation of sampling data. These abilities must facilitate analysis for current, monthly, quarterly, and yearly reports, as well as batch related reporting. It should enable the trending of one site, multiple sites, for one room or multiple rooms/departments. Further, it should track micro-organism identification and the locations where contamination is found, personnel monitoring, trending by lot, or reverse trace reporting based on equipment, media lot, and other sampling data collected. The end goal is to deliver reporting and trending capabilities for Issue Visibility, Root Cause Analysis, Pattern Recognition, and proof of State of Control. Case Study A real world example of how pattern recognition, and ease of access to trends, assists in root case analysis: In this example a company found the root cause using an annual trend graph, and correlating the spikes (action level events) with other data in the data warehouse. In January 2013, changes were being made in the manufacturing area, based on these changes the gowning requirements for certain Grade D areas were upgraded to include hairnets, boot covers and lab coats. All personnel were trained on the new gowning requirements. The new monitoring locations were established in the Grade D rooms affected by the change, and a regular monitoring schedule (weekly) was put in place. In February 2013 an action level excursion occurred at a site in a Grade D room. The sample was a floor surface sample. The room was for production support, there was no product contact in the room, it contained gauges, water buffer controls, and tanks, and it was a production support area. The excursion occurred only at the one site in the room, all other sites were within levels. Using the Novatek Environmental Monitoring System the data was reviewed, it was determined it was a singular site, no other sites were affected. Also, there was no creep up, it was a singular occurrence and previous monitoring at that same site did not result in any abnormal counts. The corrective action was to sanitize and retest to verify the room was back in control. In May 2013, an action level excursion occurred at the same site. The limit was again breached, at that single site in the room. The data was again reviewed and the results were the same. Only the singular site was showing the high count, no prior increase of counts at that site, or any other site in the area. The corrective action was to sanitize and retest to verify the room was back in control. In August 2013, the first week after restarting production after an annual shutdown, monitoring at the same site again resulted in an action level excursion. An investigation was conducted; the following items were verified during the root cause analysis of the event: Verification of the production schedule, no production was ongoing at the time of the samples. Verification of the metal grate floor above the site, no issues were found. Risk Management in Environmental Monitoring: Should you be spotting it sooner? 4

5 Verification of the ceiling above the site, no issues were found. Inspection of the HEPA filter Additional testing for air contamination Inspection of all utility systems, gauges, control panels, etc..., in the room was done. No issues were found. The root cause was still undetermined and the corrective action was to sanitize and retest to verify the room was back in control. In November 2013 the same event occurred. Once again, inspections were done on the room. This included ceilings furnishings, equipment gauges, and control panels. Once again the cause was not determined. In January 2014 the company was conducted their annual data review. The Novatek Environmental Monitoring System was used to evaluate trends in the facility. With the computerized system, reviewing the data was much faster, and patterns were recognized. Based on this, the annual review SOP had been revised to include a more substantial look at the facility trends. During this review the root cause of the contamination at the singular site was found. The graph of the room where the site was located is displayed below. The person reviewing was able to clearly see a pattern. The action level events were occurring on a quarterly basis. The individual hits were not telling, but the pattern was telling. The pattern solved the issue (looking at month, quarter, etc did not help. Only the annual trend was able to facilitate discovery of the root cause and resolving it. Equipped with this information, the investigation into other activities in the room, in the same time frame, resulted in finding the metrology schedule for the gauge, in front of the affected site, was synchronized with the action level events. Further, the same person entered the room to perform the calibration activities each time. An interview with the person was conducted and it was determined that he had not being trained on Risk Management in Environmental Monitoring: Should you be spotting it sooner? 5

6 the change in the gowning requirements. He was simply putting on a lab coat and entering, he was following the old procedure for room access. The root cause was determined to be: Manual training records were deficient Electronic card access was not denied for untrained or ineligible personnel. Alert level excursion pattern settings in the computerized system had a timeframe that was too tight. The system was able to send out action level notifications based on x number of alerts occurring within y number of samples at any given sample point(s). The y value was set too low. Posted placards were not displayed at the entry points to controlled areas to clearly indicate gowning requirements. Once the root cause was determined the company was able to put in place the corrective actions to prevent this occurrence. The measures put in place were: The training records were converted to electronic format. They were incorporated into the computerized system. Once the training records were computerized the company was able to link them to a notification system which triggered s to management when training is either not completed or not successfully completed. Key card access is denied to personnel who have either not had the required training or if their training / qualification has expired. Placards are posted at all controlled area access points. These placards clearly indicate the gowning requirements and the qualification required for access. SOP on investigations of Alert and Action level events were updated to include metrology schedule of room access where events occur as standard criteria to review and include. Settings, in the computerized system, which trigger the notification of patterns of alert and action level incidences, were modified to be more sensitive for recognizing long term patterns in the data. With over a year of data these settings would be more effective than in the first year. The example above clearly illustrates the benefits of having a holistic system, one which provides advanced data mining, and reporting abilities, as well as notifications and pattern recognition. Conclusion Environmental monitoring software, that is designed to remediate risk, focuses on automation to enforceprocess controls (SOP/Workflow). A system which enforces best practices will substantially reduce risks associated with Environmental Monitoring processes. Using dedicated environmental monitoring software provides the ability to discern adverse trends early, allowing companies to act quickly to correct issues, while the product is being made. Implementation of a computerized, paperless, best-practices solution, to control environmental monitoring, and utility monitoring, provides an immediate and tangible ROI. The key benefit is the real-time availability of reliable data that can effectively and accurately provide documented evidence supporting product release and ensuring regulatory compliance. Risk Management in Environmental Monitoring: Should you be spotting it sooner? 6

7 Appendix/References FDA Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing-Current Good Manufacturing Practice, 2004 USP <1116> Microbiological Control and Monitoring of Aseptic Processing Environments, 2012 Author Information Susan B. Cleary, B.Cs, M.B.A. is the Director of Product Development at Novatek International. Previously holding the position of Program Manager and Lead Software Engineer for three applications; Finished Products Analyzer, Raw Materials Management and Environmental Monitoring software programs. Susan has 15 years of experience in designing, developing, implementing and managing large scale LIMS and Quality Management software implementations while working with both Pharmaceutical and Biotech companies to capture their requirements and provide fully validated turnkey systems. Susan specializes in Environmental Monitoring processes and works with clients to streamline their procedures and manage their data more effectively. Risk Management in Environmental Monitoring: Should you be spotting it sooner? 7

8 Novatek International Novatek International provides a new breed of allencompassing, process-driven laboratory information management system (LIMS) and other software solutions that target the pharmaceutical, biotech and other healthcare industries. Our unique portfolio of out-of thebox, easy to use, software solutions features specialized modules that help you manage all aspects of your quality environment with less effort and time. Novatek delivers solutions that go beyond LIMS for total enterprise wide automation. ntint.com 4480 Cote de Liesse Suite 355 Montreal, Quebec, H4N 2R1 Canada Phone: Fax: Copyright 2014 Novatek International All Rights Reserved Risk Management in Environmental Monitoring: Should you be spotting it sooner? 8