Package Testing and Validation
Regulatory agencies’ concerns for labeling and packaging of a medical device lead to product quality scrutiny. Package validations are a key component of all medical device design history files and regulatory submissions. Whether the device is sterile or nonsterile, packaging of the product to ensure it arrives as intended is of the utmost importance.
Our technical experts approach these validations by looking at the components of the packages both individually and as a whole. Packaging validation consists of three components: package and seal integrity testing, accelerated aging or shelf life stability, and simulated distribution testing. Our validation and ongoing testing incorporate the aging of the product packaging to support shelf life stability and product expiration labeling. In addition, our validation design will evaluate package integrity, seal strength, and burst properties, to verify that during distribution of the final finished devices – whether boxes or cartons – the packaging remains intact.
Seal Integrity Testing
Regulations dictate that the seal strength and specification limits be determined for pre-sterilization sealer performance verification (high, low, and standard parameter settings) and seal strength consistency qualified for post-sterilization production, shipping, and shelf-life qualifications.
Seal Tensile Strength [ASTM F 88]
This method determines the strength of a specific area of the seal for a medical device package.
Burst Strength [ASTM F 1140]
This method determines a package’s ability to resist internal pressure and measures the strength of the package seals.
Package Integrity Testing
Regulations require the integrity of sterile packages be maintained during the production, shipping, and shelf life of the product. Physical testing for package leaks has been shown to be more sensitive than the microbial challenge test and is generally the preferred method.
Bubble Emission Test (ASTM F 2096 or FPA/SPMC 005-98)
This method, which covers the determination of gross leaks in flexible packaging, is applicable to nonporous packaging and to porous packaging that has its porous component sealed using a blocking agent. It is used to detect leakage of air through a channel in the seal or pinhole in the package.
Compression Test [ASTM D 642]
This method covers compression tests on shipping containers (e.g., boxes and drums), their components, or both.
Drop Test [ASTM D 5276]
This method is used in evaluating the capability of a container to withstand the sudden shock resulting from a free fall, or to evaluate the capability of a container and its inner packing to protect its contents during the sudden shock resulting from a free fall.
Dye Penetration [ASTM F 1929]
This method, which covers the determination of gross leaks in flexible packaging, is applicable to porous and nonporous medical device packages. It is used to detect small leaks in materials or seals of packages where harmful biological or particulate contamination may enter.
Liquid Dye Immersion [USP <1207.2> and USP <381>]
This method is used to detect failures, such as cracks, seams, and laminations, due to leaks or lack of fusion. The dye immersion method can be used on various types of materials, such as nonporous, metallic materials (ferrous and non-ferrous) and nonmetallic materials (glazed ceramics, certain nonporous plastics, and glass).
Whole Package Microbial Aerosol Challenge with Sterility Test
This microbial barrier test evaluates the ability of an intact, production package to maintain its sterile barrier until it reaches its end of use point. In the test chamber, the package is subject to an aerosol challenge, which may be performed under dynamic or static conditions.
Whole Package Microbial Talc Challenge with Sterility Test
This microbial barrier test is used to evaluate the ability of an intact, production package to maintain its sterile environment until it reaches its point of end use.
Microbial Ingress / Immersion Challenge
This microbial barrier test is used to assess the ability of a non-porous package to provide a microbial barrier.
Transportation/Distribution Simulation Testing
Manufacturers must adequately evaluate the ability of the package and shipper to protect the product through the handling, shipping, and distribution environments. Damage such as puncture, abrasion, and seal failure may result.
Distribution Simulation Shipper Test [ASTM D 4169 – DC 13]
This test method is performed by subjecting shipping units to a test plan consisting of a sequence of hazard elements (e.g., shock, drop, vibration, or compression) that are encountered in various distribution environments.
Transportation Simulation Test [ISTA Project 1A, 2A and 3A]
These tests provide a means for manufacturers to predetermine the probability of the safe arrival of their packaged products at their destination through the utilization of tests developed to simulate the shocks and stresses normally encountered during handling and transportation.
Thermal Controlled Transport Packaging Test [ISTA 7D]
This method covers the thermal performance testing of packaged products to evaluate the effects of external temperature exposure.
ISTA Environmental Conditioning [ISTA Series]
Temperature cycling sequence. This series of testing will help mimic the environmental conditions your product and packaging will encounter, heat, humidity and vibration to ensure package performance.
ASTM Environmental Conditioning [ASTM D4332]
This practice is used to simulate particular field conditions that a container, package, or packaging component may encounter during its life or testing cycle.
Accelerated Aging/Shelf Life Expiration Dating Studies (ASTM F 1980)
Accelerated Aging is a key component of the overall packaging validation for medical devices. Following ISO 11607, package validation includes accelerated aging and the corresponding integrity testing as well as simulated distribution and its subsequent integrity testing.
Accelerated aging serves as key interim data to support product shelf life dating until real-time data are available. When needed, will provide recommendations regarding aging of additional samples—if appropriate and if chamber space would allow. This additional aging may be useful in the event of a future issue to support shelf life extension or supplemental data.
Product and Environment Validation
WuXi AppTec’s technical and regulatory experts leverage their scientific knowledge of microbiology for product and manufacturing environment validations. We validate cleaning, disinfecting and sterilizing of reusable and third party reprocessed devices processes in addition to sterilization validation of both radiation and ethylene oxide (EO).
We also support ongoing product testing through dose audits of sterilized products. The manufacturing environment validation we offer includes environmental monitoring of water, surface, air, and personnel protective equipment (PPE), as well as surface disinfectant efficacy studies. We will also support continued testing for your validated manufacturing environment.
Without a standard definition of clean, the responsibility falls to device manufacturers to ensure their cleaning and disinfection and/or sterilization instructions are adequate and comprehensive. Regulatory bodies expect device manufacturers to validate their instructions to demonstrate a reliable and repeatable process using worst-case scenarios. Our team will work with you to develop a test plan that meets these stringent guidelines. Our test plans and final reports support regulatory submissions, product adoptions, and testing confidence on device or process changes. Our approach remains the same – we construct a protocol and challenge the device to ensure that it meets the latest regulatory expectations.
All sterilization processes require validation of the efficacy and reproducibility of the process. WuXi AppTec offers a full range of services in this area – from stand-alone testing to complete validation management.
Our technical experts collaborate with you to design the validation based on a sterilization method and manufacturing process that will meet regulatory requirements. We continue to support device testing with bioburden, sterility, microbial identification, and additional ongoing product safety testing.
Radiation Sterilization Validation
For validation of radiation (gamma, electron beam, or X-ray) sterilization, critical steps are outlined in ISO and AAMI standards. As part of the performance qualification, a dose setting or dose substantiation study must be performed to demonstrate the adequacy of the minimum dose to achieve the desired sterility assurance level (SAL). Several methods are available for validation of the minimum sterilization dose, and the choice of method is dependent on a number of variables. Our study design for complete radiation validation studies is for a specific product and process, and all aspects of the studies follow the requirements of ISO and AAMI standards.
Dose Audit Services
With more than 25 years of experience and extensive knowledge of the regulatory requirements, WuXi AppTec offers unmatched expertise and the convenience of three levels of dose audit services. Your choice of service level depends on how much of your company’s time, manpower, and expertise you want to commit to your ongoing dose audit program.
Three Levels of Dose Audit Services
- At the most basic level, we provide only testing services while you schedule and manage all aspects of the sterilization process and develop all of the documentation to present an organized and compliant study.
- In addition to the testing, we can also handle all of the sterilization services for you, and you would be responsible only for producing the final documentation showing compliance.
- We can take care of everything. You simply give us your product samples, and, at the end, we provide you with a complete summary report manual showing dose audit compliance.
Ethylene Oxide (EO) Sterilization Validation
For validation of ethylene oxide (EO) sterilization, critical steps are outlined in the ISO and AAMI standards. As part of the performance qualification, a microbial challenge must be performed to demonstrate the adequacy of the process to achieve the desired sterility assurance level (SAL). One of the most utilized methods is the half-cycle (overkill) method, which uses a biological indicator (BI) challenge, typically 106 spores of Bacillus atrophaeus. Our study design for complete EO validation is for a specific product and process, and all aspects of the studies follow the requirements of ISO and AAMI standards.
Ethylene Oxide (EO) Testing
Medical devices that are sterilized by ethylene oxide (EO) must be shown to have adequately degassed EO residues before the devices may be used. Analyses are performed for EO and ethylene chlorohydrin (ECH) according to current ISO and AAMI standards (10993-7). The allowable limits are for EO and ECH; no exposure limits have been set for ethylene glycol (EG). The allowable limits are based on patient contact duration and are designated as limited (≤24 hours), prolonged (>24 hours and ≤30 days), or permanent (>30 days).
- EO Residual Panel (Water Extraction) – EO, ECH, EG
- EO Residual Panel (Headspace Extraction) – EO, ECH, EG
- EO Water Analysis
- EO Water Analysis – Exhaustive
- EO Headspace Analysis
- EO, ECH (Water Extraction)
- EO (Headspace Extraction), ECH (Water Extraction)
- ECH (Water Extraction)
In complex manufacturing environments, disruptions in production and unplanned downtime are inevitable. To support your environmental monitoring quality program, WuXi AppTec focuses on testing your water, air, and surface samples.
Our team will coordinate with your manufacturing facility to quickly test and report results. Our scalability supports overflow sample collection as well as large-volume testing when the unexpected occurs.
Microbial Sampling Tests
Environmental Air and Surface Sample
Growth on each environmental air (plate or strip) or surface (contact plate—e.g., RODAC) sample is enumerated. Gram stain and/or genus/species identification is available.
These assays are used as an indicator of the water quality. Sample aliquots obtained from a water system are evaluated for a number of viable microorganisms. Specifically, coliform counts and pseudomonas counts can be enumerated.
Surface Disinfectant Efficacy
Study designs commonly follow the USP <1072> regulatory guidelines. In addition, our standard methods (ASTM, AOAC, USP, ISO, etc.) can be modified, expanded, or customized. Our program design evaluates the log reduction of a disinfection process on hard surfaces. The study challenges a disinfectant surface in combination with a variety of microorganisms.
We partner with manufacturers to support the feasibility study and validation of the disinfectant(s) that works best for your facilities. Our regulatory experts will work with you to design a validation that meets the latest regulatory guidelines. Our flexible study designs combined with our microbiology expertise enable us to build a comprehensive, customized study that best suits your needs.