1. SELECTING AND MANAGING CONTRACT STERILIZERS AND TESTING LABORATORIES
Pacific BioLabs Inc.
(510)

2. CONTRACT STERILIZERS
Written agreement between the contract sterilizer and the device manufacturer is required by 21 CFR (e), Medical Devices, processing, labeling or repacking

3. WRITTEN AGREEMENT MUST INCLUDE:
Instructions for maintaining proper records
Acknowledgement that the device is non-sterile and awaiting processing
Detailed specifications for the sterilization process
Division of responsibilities

4. DIVISION OF RESPONSIBILITY
The device manufacturer is ultimately responsible for the sterility of its products
The contract sterilizer is responsible for a quality control system for steps under its control
Therefore, ……..

5. RESPONSIBILITIES OF MANUFACTURER
Ensure devices are sterile by confirming quality control system of contractor
Validation of the process
Ensure process controls are appropriate
Maintain records of specification & evidence they were followed
Product release

6. RESPONSIBILITIES OF CONTRACT STERILIZER
All requirements of the quality system regulation that apply to its operations
Equipment installation, maintenance, and equipment calibration
Installation and operation qualifications
Building adequacy
Personnel training
Environmental controls

7. RESPONSIBILITIES OF CONTRACT STERILIZER (cont.)
Quality system requirements:
Process controls
Documentation and record keeping
Acceptance of manufacturing materials
Procedures for handling process deviations
Any other requirement of the written agreement

8. COMMON PROBLEMS FOUND BY FDA
Manufacturer does not assume responsibility for sterilization performed by the contract sterilizer
Communication between the two parties of changes
Product is released following sterilization without approval of device manufacturer

9. TESTING LABORATORY Manufacturing Facility Contract Laboratory
Contract Sterilizer

10. LAB ATTRIBUTES Quality System FDA Track Record Experienced Personnel
SOP
Calibrated equipment
Training
FDA Track Record
Experienced Personnel
Industry Reputation
Committed Client Services

11. STERILIZATION QUALITY TESTS
Bioburden
Bioburden Recovery Validation
Sterility
Bacteriostasis and Fungistasis
Biological Indicators
Pyrogen or Bacterial Endotoxin
Inhibition and Enhancement

12. STERILIZATION QUALITY TESTS (cont.)
Package Integrity
Chemical Residuals
Environmental Monitoring
Microbial Identification

13. BIOBURDEN Webster’s Medical Device bio (Greek) – life, living
burden – that which is carried, load
Medical Device
Population (number and types) of viable microorganisms on a product and/or a package

14. BIOBURDEN TEST Three steps Bioburden Recovery Validation
Removal of microbes from a product
Culturing on a medium appropriate for growth
Enumeration
Bioburden Recovery Validation
Demonstrates the adequacy of the steps above

15. BIOBURDEN METHODS Pour plating Spread plating Membrane filtration
Automated microbiology systems

16. STERILITY TESTS Product Sterility Biological Indicators (BI) Sterility
Membrane filtration
Direct transfer
Biological Indicators (BI) Sterility
Testing the BI by placing it in microbiological growth medium

17. STERILITY TEST VALIDATION
Bacteriostasis and Fungistasis (B & F)
Test using known organisms to demonstrate whether the combination of the product and sterilization method do or do not inhibit microbial growth

18. STERILITY TEST USP vs. AAMI/ISO
Two microbiological media
SCDM and FTM
B&F (6 organisms)
AAMI/ISO
One microbiological medium
SCDM
B&F (3 organisms)

19. BIOLOGICAL INDICATOR TESTS
Three quality attributes may be measured:
Species identification
Population
Resistance
D-Value
Z-Value

20. BACTERIAL ENDOTOXIN TEST
Endotoxin = Pyrogen
Bacterial Endotoxin Test = LAL Test
Gel clot method
Photometric techniques
Photochromogenic
Turbidimetric

21. INHIBITION AND ENHANCEMENT TEST
Validation of the LAL test
3 lots of product must be tested

22. DEVICE PACKAGING 21 CFR
“Each manufacturer shall ensure that device packaging and shipping containers are designed and constructed to protect the device from alteration or damage during the customary conditions of processing, handling, and distribution”

23. DEVICE PACKAGING 21 CFR
Package integrity is required to maintain the microbial barrier and sterility of the product
Expiration dating
Required for IVD’s and certain other devices that may degrade over time
If label includes expiration, you must have data to back it up

24. PACKAGE INTEGRITY TESTS
Dye Penetration
Microbial Challenge
Burst
Creep
Seal peal

25. CHEMICAL RESIDUALS (EO ONLY)
EO (ethylene oxide)
ECH (ethylene chlorohydrin)
EG (ethylene glycol)
No longer required

26. ENVIRONMENTAL MONITORING
Conducted in-house
Laboratory field technicians conduct sampling at manufacturing facility
Samples collected by sponsor’s personnel and incubated/counted at testing laboratory

27. ENVIRONMENTAL MONITORING TESTS
Non-viable particles
Viable particles
Bacteria
Soybean Casein Digest Medium (SCDM)
30 – 35 °C
Yeast and Mold
Sbouraud Dextrose Agar (SDA)
20 – 25 °C
Growth promotion required

28. MICROBIAL IDENTIFICATION
Morphological characterization
Colony description, Gram stain
Identification to genus and species level
Phenotypic
Genotypic

29. MICROBIAL IDENTIFICATION
Biochemical Tests
Vitek
Fatty Acid Analysis
MIDI
Carbon Utilization
Biolog
Genetic Based Technology (preferred)
RiboPrinter

30. MICROBIAL WATER TESTS Total Heterotrophic Counts Yeast and Mold Counts
Coliform Determinations
Thermophiles Counts
Anaerobes counts
Pseudomonas screening

31. WATER TESTS Choice of Media Choice of Incubation Temperature
Plate Count Agar
Soybean Casein Digest Agar
R2A
Tryptone Glucose Extract
Choice of Incubation Temperature
30-35°C, 20-25°C
Choice of Incubation Times
2, 3, 5 or 7 days

32. THANK YOU
Q & A