1. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 1 of 23 Bioburden Failure Analysis An E. coli strain being plated for identification.

2. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 2 of 23 Presentation Outline Important environmental monitoring data to collect and analyze Most common reasons for exceeding validated bioburden limits Containment & corrections Corrective actions & preventive actions Conducting a supplier audit of environmental monitoring Training & quality objectives

3. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 3 of 23 What to do first Double-check your math for calculation of bioburden and trend of bioburden Identify the organism(s) found Confirm effectiveness of cleaning agent(s) on organism(s) found Re-sample work environment (duplicate conditions of previous sample if possible) Sample additional locations

4. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 4 of 23 Records you should collect Raw data from environmental monitoring Trend analysis of environmental monitoring Identification of organisms found Cleaning logs Preventive maintenance logs Temperature data logs Device History Records Training Records

5. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 5 of 23 Documents you should collect Maps of controlled environment and warehouse – Location of personnel – Location of specific raw materials/components – Process flow Gowning procedure Preventive maintenance procedure(s) Cleaning procedure(s)

6. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 6 of 23 Most Common Causes People not following gowning procedures Inadequate gowning procedures Inappropriate storage conditions for components Failure to remove secondary packaging or clean primary packaging outside controlled environment Failure to follow cleaning schedule Inadequate cleaning and preventive maintenance

7. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 7 of 23 Supplier Audits Supplier qualification audits should be conducted on-site—not remotely Types of suppliers that should include a review of environmental monitoring, gowning and cleanroom cleaning procedures – Contract manufacturers of finished devices – Contract packagers – Component suppliers for sterile devices

8. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 8 of 23 When NOT to Audit Remotely Onsite visits facilitate the building of supplier-customer relationships. Touring facilities and watching demonstration of processes improves understanding of a supplier’s processes better than reading documents and records can. Cleanliness and capabilities of suppliers are best evaluated onsite, where camera angles can be used to crop out important details Sometimes suppliers misrepresent their capabilities by showing photographs on their website of other companies.

9. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 9 of 23 “Witch Hunts” Request copies of documents and records in parallel with requesting a supplier corrective action (SCAR)

10. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 10 of 23 SCAR Effectiveness Check http://www.medicaldeviceacademy.com/supplier-auditing-tool-kit

11. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 11 of 23 If supplier delays SCAR… How do you monitor production processes? Step 7 Output is the DHR for each production lot. Input is the production work order or job order. Step 2Step 3 Step 5 Step 6 Sample calibration records. Sample maintenance records. Sample validation & re-validation records. Sample environmental monitoring and cleaning records. Step 4 Step 1: Describe the process for controlling production processes. Reference supplier’s procedures and forms, including revisions of documents. Sample training records for person(s) performing manufacturing. Look for effectiveness of training and competency.

12. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 12 of 23 Remote Auditing “Any time you can audit in a conference room, you could probably do the audit remotely.” http://medicaldeviceacademy.com/4-ways-make-best-use-remote-audits/

13. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 13 of 23 Root Cause Analysis

14. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 14 of 23 Containment Which lots? If specific cause is unknown, there should be statistical rationale for the bracketing based upon sampling and trend analysis of bioburden. Identify product and/or raw materials as nonconforming (i.e., initiate an NCR) Don’t contaminate your “good” product

15. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 15 of 23 Corrections Re-sterilization of product (if you do not have this validated, evaluate the adverse effects of re- sterilization) Conducting a recall Scrapping product Cleaning product (rework procedures with an evaluation of the adverse effects of rework) Cleaning—a lot!

16. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 16 of 23 Corrective Actions Changes to supplier environmental controls Changes to raw material storage Changes to gowning procedures Increasing the frequency of cleaning Changing the disinfection solution & creating a rotating schedule More frequent replacement of HEPA filters Retraining

17. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 17 of 23 Hairnets & Gloves 1 2

18. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 18 of 23 Preventive Actions Most companies struggle to identify purely preventive actions Bioburden trend analysis is an excellent source Don’t wait until you have an excursion. Examples of Preventive Actions: – Monitoring raw material bioburden – Improved gowning procedures – Increasing the frequency of cleaning – Rotating disinfecting solutions – Preventive maintenance of HEPA filters

19. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 19 of 23 Effectiveness Checks No further excursions Re-audit of environmental monitoring Training exams Bioburden trend analysis

20. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 20 of 23 Training Importance of cleanliness – “As part of their training, personnel shall be made aware of device defects which may occur from the improper performance of their specific jobs.” 21 CFR 820.25(b)(1) Personnel should be able to answer hypothetical questions about what to do if specific excursions occur Personnel should be able to describe and demonstrate proper gowning and cleaning procedures

21. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 21 of 23 Quality Objectives Compliance with preventive maintenance schedules, cleaning schedules and completion of cleaning records Reduction in the bioburden found at various sampling points

22. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 22 of 23 Q&A

23. Rob Packard, President www.MedicalDeviceAcademy.com rob@13485cert.com Slide 23 of 23 Need help? Contact me. Rob Packard rob@13485cert.com +1.802.281.4381 rob13485