SELECTING AND MANAGING CONTRACT STERILIZERS AND TESTING LABORATORIES

SELECTING AND MANAGING CONTRACT STERILIZERS AND TESTING LABORATORIES Pacific Bio. Labs Inc. (510) 964 -9000 info@Pacific. Bio. Labs. com

CONTRACT STERILIZERS n Written agreement between the contract sterilizer and the device manufacturer is required by 21 CFR- 801 -150(e), Medical Devices, processing, labeling or repacking 2

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

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

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

RESPONSIBILITIES OF CONTRACT STERILIZER n 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 6

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

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

TESTING LABORATORY n Manufacturing Facility n Contract Laboratory n Contract Sterilizer 9

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

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

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

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

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

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

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

STERILITY TEST VALIDATION n 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 17

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

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

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

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

DEVICE PACKAGING 21 CFR 820. 130 “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” 22

DEVICE PACKAGING 21 CFR 820. 130 n Package integrity is required to maintain the microbial barrier and sterility of the product n 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 23

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

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

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

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

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

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

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

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

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