Effective Use of Environmental Monitoring Data Trending
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The document outlines the effective use of environmental monitoring (EM) data trending in the context of aseptic processing, emphasizing its importance for regulatory compliance and proactive management of contamination issues. It discusses learning objectives, regulatory requirements, methods for evaluating trends, and the significance of sharing data across departments to facilitate corrective actions. Additionally, it highlights how trending data can demonstrate compliance, improve sanitation practices, and aid in investigations related to microbial contamination.
Effective Use of Environmental Monitoring Data Trending
- 1. Effective Use of Environmental Monitoring Data Trending Kim Van Antwerpen Regional Quality Compliance Specialist Siemens Medical Solutions (PETNET) IVT Life Sciences Aseptic Processing Europe November 2012
- 2. For more information on environmental monitoring and data monitoring, please visit www.ivtnetwork.com for a wide variety of SOPs, templates, journal articles, and training videos. Use promo code SLIDE1 for a 10% discount.
- 3. Learning Objectives • Why we perform EM Trending • What Data to Collect • Trend Evaluation • Interpreting and Sharing EM Data • Examples of Trending “I think you should be more • Practical Use of EM explicit here in step two” Trending Data • Learning Exercises
- 4. EM Data Trending - Background Why do we perform EM trending? We trend information gained from environmental monitoring sampling for the purposes of: – Following regulatory requirements – Understanding the “health” of the Production facility – Understanding the bacterial flora of the facility – Having a method to communicate environmental trending data to the rest of the company – The ability to be proactive with corrective action for bacterial issues
- 5. Why do We Perform EM Trending? Following Regulatory Requirements
- 6. Why do We Perform EM Trending? Understanding the “health” of Is the cleaning/ the Production Is the sanitizing facility environment program robust clean overall? and performed adequately? Does the data show good Are there control of “problem aseptic areas”? conditions?
- 7. Why do We Perform EM Trending? Understanding the bacterial flora
- 8. Why do We Perform EM Trending? Communicate EM Communicating the EM data gives data to the other departments knowledge of the Company microbial levels in the facility and allows for the development of corrective action plans The information must be shared both with management and with the personnel on the production floor
- 9. Why do We Perform EM Trending? Be proactive with contamination issues
- 10. Regulatory Requirements – EU Guidelines EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use – Part I – Chapter 6, Quality Control “For some kinds of data (e.g. analytical tests results, yields, environmental controls) it is recommended that records are kept in a manner permitting trend evaluation.” PIC/S: Recommendation on Sterility Testing, 10. Environmental Monitoring “Records should be maintained of the numbers and type of organisms isolated and results presented in a format that facilitates early detection of trends.”
- 11. Regulatory Requirements Regulatory Requirements –Code of Federal Regulations (CFR) 21CFR 211.113 “Control of Microbiological Contamination” “(b) Appropriate written procedures, designed to prevent microbiological contamination of drug products purporting to be sterile, shall be established and followed.”
- 12. Regulatory Requirements – FDA Guidance FDA Guidance for Industry - Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice (2004) Section (X) “Laboratory Controls” (A.2) “Establishing Levels and a Trending Program” Environmental monitoring data will provide information on the quality of the manufacturing environment. Each individual sample result should be evaluated for its significance by comparison to the alert or action levels. Averaging of results can mask unacceptable localized conditions. The quality control unit should provide routine oversight of near-term (e.g., daily, weekly, monthly, quarterly) and long-term trends in environmental and personnel monitoring data.
- 13. Regulatory Requirements – FDA Guidance (continued) Trend reports should include data generated by location, shift, room, operator, or other parameters. The quality control unit should be responsible for producing specialized data reports (e.g., a search on a particular isolate over a year period) with the goal of investigating results beyond established levels and identifying any appropriate follow-up actions. Significant changes in microbial flora should be considered in the review of the ongoing environmental monitoring data. Written procedures should define the system whereby the most responsible managers are regularly informed and updated on trends and investigations.
- 14. Regulatory Requirements – United States Pharmacopoeia (USP) …information is periodically evaluated to establish the status or pattern of that program to ascertain whether it is under adequate control. When data are compiled and analyzed, any trends should be evaluated by trained personnel. …critical to review results over extended periods to determine whether trends are present. The microbial control of controlled environments can be assessed, in part, on the basis of these trend data. Periodic reports or summaries should be issued to alert the responsible manager. Trends that show a deterioration of the environmental quality require attention in determining the assignable cause and in instituting a corrective action plan to bring the conditions back to the expected ranges. … an investigation should be implemented and an evaluation of the potential impact this has on a product should be made.
- 15. Obtaining Data and Trending Analysis Viable and Non-Viable Particles Personnel Water (WFI) Microbial Plant Identifications Gasses
- 16. Obtaining Data and Trending Analysis What is Trended? Data that has meaning Trending may be labor intensive - compiling data will take time, so… Try to identify areas of concern prior to beginning a trending program!
- 17. Obtaining Data and Trending Analysis For Example Are you interested in or required to report: -Frequency of observations of alerts and actions? -Types of organisms identified? -Trends by shift or manufacturing group? -Seasonal trends? -Trends for individual rooms vs. areas or sample sites vs. rooms? -Personnel trends? -Trends during filling vs. non-filling times?
- 18. Looking for Trends Within Trends What makes a Trend? And how do you find one? -Lower personnel excursions -Repeat observations of over time certain flora -Fewer EM excursions after a -Multiple excursions in one CAPA day or in one room -Reduced excursions -Seasonal trends following training -Trends for an individual -Fewer observations of CFU person after change in sanitizer or -Trends by floor/building, lot after making Engineering type, or shift control changes
- 19. Looking for Trends Detecting an Adverse Trend Adverse trends can come from many different root causes Weather Building Poor System Cleaning Failure Adverse EM Trend Change in Seasonal Personnel
- 20. Finding a Trend What should be done about an Adverse Trend? Dig Deep - A trend should warrant a deeper level of investigation • Interview persons/shifts involved • Review Maintenance Records • Try to find the “smoking gun” • Introduce CAPA to solve • Put Production On Hold
- 21. Interpreting and Sharing EM Data Methods for Trending • Electronic (EM Trending Software) +Real time trending +Automatic notification of issues – $$$ • Manual (Compiled into a spreadsheet, made into graphs) +Inexpensive +Flexible - Not real time
- 22. Example of a Trending Program
- 23. Example of a Trending Program Grade A/Class 100 Trend of Viable Particle Action and Mold Observations 12 # of Action # of Observations 10 Level Observations 8 6 4 # of Mold 2 Observations 0 May March November July January April June August February October September December Month
- 24. Example of a Trending Program Observations of Personnel Viable EM Action Level Excursions 35 # Glove # of Action Level Observations 30 Observations 25 # of Gown 20 Observations 15 Linear (# Glove 10 Observations) 5 Linear (# of Gown 0 Observations) November June July January October December September March April August May February Month
- 25. Example of a Trending Program Observations of Water (WFI) CFU 12 10 # of Action # of Actions/Alerts 8 Level Excursions 6 # of Alert Level 4 Excursions 2 # of sub- Alert Level Excursions 0 May March November July January April June August February October December September Month
- 26. Example of a Trending Program Action Alert Mold Grade A Grade A Grade C Grade B Grade C Grade B Grade B Grade C Grade Grade D Grade D C
- 27. Example of a Trending Program Bacterial Identification by Genus 25 Warm summer months - sweating 20 # of Colonies Observed Bacillus Dry skin in Winter 15 Fusarium Windy or Wet Weather 10 Corynebacterium Micrococcus 5 Staphylococcus 0 November June July January October December September March April August May February Month
- 28. Using EM Data Generated by a Trending Program The data generated by an EM trending program can be used for: – Demonstrating a level of compliance to regulatory EM requirements – Showing Efficacy of Sanitization and Gowning Processes – Supporting Investigations – Understanding flora – Proactively Preventing Future EM Issues – Communication
- 29. Using EM Data Generated by a Trending Program Use the data to show the level of compliance Auditors Customers Patients
- 30. Using EM Data Generated by a Trending Program Use the data to show good cleaning and gowning practices at the facility
- 31. Using EM Data Generated by a Trending Program Use the data to support investigations Root Cause Defend Deviations Determine Product Impact
- 32. Using EM Data Generated by a Trending Program Global Thinking – Outside of the Box and Beyond • Is this a ‘one-off’ event? • Are there other areas of the facility that could be affected by the same issue? • Does this issue occur over multiple shifts/between buildings/over a long time span? • Who and what processes are affected up- and downstream of this problem? • Can I implement global preventive action to keep this from happening again?
- 33. Using EM Data Generated by a Trending Program Use the data to understand the flora and use it for corrective action and training
- 34. Using EM Data Generated by a Trending Program Use the data to prevent future EM issues -Change Control -Training -Plant and Process Engineering “I’ll have an ounce of prevention”
- 35. Using EM Data Generated by a Trending Program Use the data to Lab Communicate Senior Leadership Manufacturing Environmental Review EM Board Quality Systems Data Engineering Operational Excellence Maintenance
- 36. Using EM Data Generated by a Trending Program The Environmental Review Board (ERB) is a management review group who meet once per month to review and discuss the previous month’s EM trending data. The ERB participants are cross-functional, and come from Microbiology (QC), Production, Quality (QA), Engineering, Maintenance, Compliance, and Upper Management (VP Level) The purpose of the ERB is to communicate the EM data to the facility. Often, people who work in the facility do not visualize the EM data on a regular basis. Communicating this data gives other departments knowledge of the microbial levels in the facility and allows for the development of corrective action plans.
- 37. Benefits of a Good EM Trending Program What’s in it for me? Internal to Company: • Defined path for communication of EM data to the facility • Data presented in a manner that is understandable to all experience levels • Ability to make data driven decisions and be proactive rather than reactive • Can be used to drive the number/frequency of EM observations down • Perform better deviation and excursion investigations External to Company • Thorough yet concise presentation of EM data to auditors • Clear demonstration of facility contamination control • Defend trends and individual excursions
- 38. Summary --There are many ways to design and use an EM Trending Program --Identify the basic needs of the program and customize to your facility --Use the data for showing compliance, communication, investigations, proactive improvements, and determination of the efficacy of processes
- 39. Interactive Exercise #1 – Who Ya Gonna Call? A trend in contamination over time with Gram negative bacteria is observed in a Grade C (class 10,000) controlled room. What are the potential sources of the contamination? Who do you notify of this issue? What CAPA might be implemented?
- 40. Interactive Exercise #1 – Who Ya Gonna Call? What are the potential sources of the contamination? Poor cleaning – The cleaning records are ok Personnel – A review shows that personnel are gowned appropriately and have no history of gowning excursions Water source – A drain for the compounding tanks is blocked and has periodically backed up into the room Who do you notify of this issue? Production Management – Suspend Compounding in that Room Engineering/Maintenance – To fix the problem Upper Management – Keep them in the Loop What CAPA might be implemented? Fix the drain Check to see if the water got behind walls or under flooring Perform extra sanitization of the room and surrounding rooms Ensure that staff are aware to report the problem right away Perform Risk Assessment to see if the contamination could get into the tank Inspect the other compounding rooms for similar issues
- 41. Interactive Exercise #2 – Do You See what I See? Grade B/Class 1000 EM Observations Drop-off in Alert Level Observations as issue becomes more severe – 30 more action level Spike in Alert Level observations # of Action 25 Observations – Opportunity Level for Proactive CAPA # of Observations Observations 20 Training for Sanitization performed – drop in # of 15 Observations # of Alert Level 10 Observations 5 # of Mold 0 Observations November December June March October September May July January February April August Low level of mold over time Month
- 42. Interactive Exercise #3 – Do You See what I See? EM Action/Mold Observations over Time Employ more sporicide use 30 in the Spring 25 Mold increases in the Spring # of Observations # of Action 20 Level Observations 15 Staff Training and illness management 10 # of Mold Actions increase during Observations back-to-school month and 5 cold/flu season 0 November December November March June March June October October September September May May July July January January February February April April August August Two Years of Data Month
- 43. Interactive Exercise #4 –Where did THAT come from? Types of Organisms over Time Sweaty personnel; poor 25 gowning practices due to being uncomfortable 20 Dry skin shedding - Winter # of Observations Bacillus 15 Fusarium April showers bring…June Corynebacterium 10 grass Staphylococcus 5 Dying and decaying plants 0 May July January February March April August October November June December September Month
- 44. Interactive Exercise #5 – Opportunities for Improvement Observations by Genus over Time Bacillus 21% 20% Fusarium Corynebacterium Training on aseptic Use of sporicide No CFU gowning technique Staphylococcus 8% Reduction of cardboard boxes and wood pallets in controlled areas Communicate the % of GOOD data, too Staff training; humidity control 11% 40%
- 45. Thank You!