SELECTING AND MANAGING CONTRACT STERILIZERS AND

TESTING LABORATORIES

Pacific BioLabs Inc.(510) 964-9000

info@PacificBioLabs.com

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CONTRACT STERILIZERS

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

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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

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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, ……..

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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

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RESPONSIBILITIES OFCONTRACT 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

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RESPONSIBILITIES OFCONTRACT 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

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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

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TESTING LABORATORY

Manufacturing Facility

Contract Laboratory

Contract Sterilizer

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LAB ATTRIBUTES

Quality System SOP Calibrated equipment Training

FDA Track Record

Experienced Personnel

Industry Reputation

Committed Client Services

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STERILIZATION QUALITY TESTS

Bioburden

Bioburden Recovery Validation

Sterility

Bacteriostasis and Fungistasis

Biological Indicators

Pyrogen or Bacterial Endotoxin

Inhibition and Enhancement

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STERILIZATION QUALITY TESTS (cont.)

Package Integrity

Chemical Residuals

Environmental Monitoring

Microbial Identification

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BIOBURDEN

Webster’s 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

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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

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BIOBURDEN METHODS

Pour plating

Spread plating

Membrane filtration

Automated microbiology systems

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STERILITY TESTS

Product Sterility Membrane filtration Direct transfer

Biological Indicators (BI) Sterility Testing the BI by placing it in microbiological

growth medium

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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

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STERILITY TESTUSP vs. AAMI/ISO

USP Two microbiological media

– SCDM and FTM B&F (6 organisms)

AAMI/ISO One microbiological medium

– SCDM B&F (3 organisms)

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BIOLOGICAL INDICATOR TESTS

Three quality attributes may be measured: Species identification Population Resistance

– D-Value– Z-Value

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BACTERIAL ENDOTOXIN TEST

Endotoxin = Pyrogen

Bacterial Endotoxin Test = LAL Test Gel clot method Photometric techniques

– Photochromogenic– Turbidimetric

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INHIBITION AND ENHANCEMENT TEST

Validation of the LAL test

3 lots of product must be tested

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DEVICE PACKAGING21 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”

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DEVICE PACKAGING21 CFR 820.130

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

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PACKAGE INTEGRITY TESTS

Dye Penetration

Microbial Challenge

Burst

Creep

Seal peal

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CHEMICAL RESIDUALS(EO ONLY)

EO (ethylene oxide)

ECH (ethylene chlorohydrin)

EG (ethylene glycol) No longer required

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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

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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

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MICROBIAL IDENTIFICATION

Morphological characterization Colony description, Gram stain

Identification to genus and species level Phenotypic Genotypic

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MICROBIAL IDENTIFICATION

Biochemical Tests Vitek

Fatty Acid Analysis MIDI

Carbon Utilization Biolog

Genetic Based Technology (preferred) RiboPrinter

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MICROBIAL WATER TESTS

Total Heterotrophic Counts

Yeast and Mold Counts

Coliform Determinations

Thermophiles Counts

Anaerobes counts

Pseudomonas screening

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WATER TESTS

Choice of Media Plate Count Agar Soybean Casein Digest Agar R2A Tryptone Glucose Extract

Choice of Incubation Temperature30-35°C, 20-25°C

Choice of Incubation Times2, 3, 5 or 7 days

THANK YOU

Q & A