Introduction
This document provides guidance for determining the suitability of packaging materials and the evaluation and testing of the integrity of packaging systems for sterile Medical Devices manufactured and/or packaged by GMP sites.
The Suitability of a Packaging System should be confirmed by testing the quality attributes of the medical device over its shelf life.
Studies should be executed to simulate the effects of environmental stresses, handling, and use conditions on the packaging system including, and not limited to:
- Temperature, pressure, and relative humidity extremes;
- Shock and vibrational stress (e.g., shipping trials); and
- Exposure to light.
The Microbial Barrier Properties of Impermeable Packaging Materials should be evaluated by using methods that demonstrate that the material is impermeable (e.g., dye penetration and Schopper method for determination of air permeability).
The Microbial Barrier Properties of Porous Packaging Materials should be evaluated by challenging samples with an aerosol of bacterial spores or particulates under a set of test conditions, which specify flow rate through the material, microbial challenge to the sample, and duration of tests. The microbial barrier properties of the materials should be determined by comparing the extent of bacterial or particulate penetration through the material with the original challenge.
Critical Factors That Affect Packaging System Integrity for Sterile Medical Devices include, and are not limited to:
- Packaging components composition, dimensions, coatings, and critical defects;
- Sealing/packaging operation variables of time, temperature, pressure (seal force), gas flow rates, torque limit, and energy level/frequency (radio frequency/ultrasonic);
- Processing variables of packaging components including washing, drying, siliconization, and sterilization; and
- Final product processing, such as terminal sterilization.
Quality Properties of the Final Packages produced at the both the upper and lower process parameter range limits should be considered for evaluation, including and not limited to:
For forming/assembling:
- Package completely formed/assembled,
- Product fits appropriately into package, and
- Essential dimensions met.
For sealing:
- Total continuous seal width,
- Punctures or tears,
- Material de-lamination or separation, and
- Channels or open seals.
For other closure system:
- Continuous closure,
- Punctures or tears,
- Material delamination or separation.
Final Package Visual Evaluation should be performed under specified conditions of distance, illumination, illumination source, time and magnification (if required).
The external surface of the final package should be inspected for defects such as:
- Irregularities in or on the sterile barrier materials, such as tears, cracks, holes or fractures;
- Presence of foreign material;
- Dimensional accuracy;
- Seal integrity (open or incomplete seals); and
- Presence of humidity, moisture or staining.
Sealing Equipment Commissioning and/or Qualification should include, and not be limited to:
- Verification that the sealing equipment is installed according to design criteria;
- Verification of mechanical operation (e.g., valves, hydraulic vacuum pumps, heating elements);
- Identification of utilities and instruments and elements (I/Es);
- Calibration of I/Es;
- Testing of alarm systems; and
- Verification that equipment operates properly throughout the Normal Operating Ranges (NOR).
- Successful seal strength tests such as Tensile Seal Strength tests and Burst/Creep Pressure tests on three (3) separate container lots;
- Tests performed within established critical process parameter ranges; and
- Use of closures that have been subjected to the maximum number of wash and sterilization cycles that are allowed during routine production.
Physical Testing Methods Used to Determine Sterile Medical Device Packaging System Integrity should include consideration of, and not limited to, the following:
- Internal pressure test;
- Dye penetration test;
- Gas sensing test; and
- Vacuum leak test.
Other physical methods may also be used if properly validated.
In-Process Controls (IPC) Used to Verify Packaging System Integrity include, and are not limited to, the following:
- Torque monitors for screw-capping equipment;
- Headspace analysis for products requiring inert gas headspace; and
- Visual inspection of seals.
In-Process Control Sampling and Test Procedures should include, and not be limited to:
- Number of samples to be tested per batch/lot;
- Test Methods (TM);
- Test equipment;
- Acceptance criteria; and
- Retest criteria and methods.