NAMSA is the global marketplace leader for reliable, proven testing services

The biocompatibility of medical devices, directed by ISO 10993-1, is a critical part of the medical device risk management process. Commonly referred to as biological safety, this evaluation of risk consists of the biocompatibility component, but also multiple other mechanisms that work together to accurately predict medical device biocompatibility based on individual materials and use. The use of biological evaluation plans, chemical characterization testing, biocompatibility testing and toxicological risk assessment are all necessary components of the successful mitigation of biological risks.

NAMSA’s medical device testing team is comprised of various experts, readily available to evaluate your device. These teams include chemists, material specialists, toxicologists and biocompatibility testing experts. Together, we can ensure that your safety evaluation plan minimizes unnecessary testing, maintains compliance with all pertinent standards and regulations and provides evidence for the ultimate goal of proving product safety.

A wide range of medical devices are introduced almost daily in today’s global marketplace, which is often marked with the challenge of adhering to the industry’s constantly-changing international standards and guidelines. Planning for biological safety is as much a business necessity as it is a regulatory requirement.

Any novel device must undergo assessment for biological hazards, risk characterization and toxicological risk assessment while also meeting the test requirements of varying international marketplaces and geographies.

At NAMSA, we offer a range of biological safety solutions to ensure your medical device development program is compliant, while also focusing on the most efficient means possible to complete necessary tests.

Biological Evaluation Plan
This is the first step of the biological evaluation for medical devices. This step is most often utilized for new devices not previously marketed, and may be needed for existing devices undergoing modifications. The Biological Evaluation Plan summarizes and characterizes a medical device based on the nature and duration of body contact, assesses the selection and materials of construction, reviews the manufacturing processes, identifies the biological endpoints of concern, evaluates any existing research data available and recommends and supports a strategy (plan) to address areas of remaining biological risk, which may include both chemical and biological testing.

Biological Evaluation Report
As part of a Biological Evaluation Report, NAMSA’s  biological safety experts perform an overall evaluation of a device/family of devices with specific consideration to the type of patient contact and intended clinical use, potential hazards associated with the materials of construction, the history of clinical use of the materials of construction, manufacturing process information, the results of biocompatibility and chemical characterization testing performed on the device, the clinical history of the device, and other information available within literature. The biological evaluation report is prepared according to the current requirements for the biological evaluation of medical devices (i.e. ISO 10993-1, FDA Biocompatibility Guidance, ISO 14971) using a risk management-inspired structure as outlined below.

• Risk analysis, including a review of raw materials data (at a minimum), manufacturing process/es and when available, non-clinical studies, clinical data and post-market surveillance data
• Risk evaluation (i.e., discussion based on gathered information to determine whether or not risk control measures [complementary tests] are necessary)
• Risk control (i.e., testing plan, including chemical characterization and/or biological tests to mitigate identified/remaining biological risks not appropriately addressed)
• Overall risk assessment (i.e., after implementation of risk control measures, when required, to determine whether implemented measures are sufficient to mitigate risks or whether any new risks are raised and further investigations are necessary)
• Re-assessment of risk (in the case of device changes)
• Conclusion

Toxicological Risk Assessment
This assessment evaluates the toxicity of individual chemical ingredients of the formulation used to manufacture a particular medical device. The assessment typically includes tests for chemical composition, extractables and/or leachables, and evaluation of any degradable or leachable materials to determine patient biological risk. This assessment is often a component of a Biological Evaluation Report where analytical chemistry testing is performed.

Equivalency Assessment
NAMSA’s Equivalency Assessment evaluates the equivalency of a device to another similar marketed product. A typical request includes equivalency regarding data and properties for clinical, technical and biological parameters, methods of use, materials as well as equivalent clinical, technical and biological properties performance.

Peer Review
NAMSA’s team of Board Certified Toxicologists (DABTs) are available to provide credibility as a third party reviewer and to vigorously critique scientific claims and research to ensure integrity of data and resultant claims.

Adverse Test Result Technical Memo
NAMSA’s technical experts can assist in delivering technical clarity of adverse results, associated implications and relevance to the known biological/toxicological endpoints relative to a specific medical device and regulatory pathway(s).

Gap Analyses
NAMSA offers comprehensive analyses detailing acceptable and deficient areas (Gap) between an existing set of data and new regulatory requirements for devices, including reports of remediation and sequence recommendations.

Training
NAMSA provides industry-leading biological safety training to the medical device industry. With over 2,000 attendees to date, our customized approach to applying ISO 10993 principles and other regulatory guidance in every day scenarios is unrivaled within the medical device marketplace. NAMSA provides three specialty courses focused on the biological evaluation of medical devices including: biological safety specialist certification, advanced workshops on the biological evaluation process and custom workshops focused on chemical characterization.

NAMSA, drawing from its 50+ year history of offering reliable chemical characterization and analytical chemistry solutions to clients, provides an extensive range of testing services to help secure product safety, quality and consistency during all stages of development. Our processes are the most trusted in industry and help to efficiently define device components and enable assessment of reproducibility in manufacturing and processing.

Some of our capabilities include, but are not limited to:

• CFR Monograph Testing
• Durometer Analysis
• Differential Scanning Calorimetry (DSC)
• Fourier Transform Infrared Spectroscopy (FTIR)
• Gas Chromatography-Mass Spectroscopy for Semi-Volatiles
• Gas Chromatography-Mass Spectroscopy for Volatiles
• Inductively Coupled-Plasma Optical Emission Spectroscopy for Inorganics/Metals
• Inductively Coupled-Mass Spectroscopy for Inorganics/Metals
• Liquid Chromatography-UV/VIS Spectroscopy for Non-Volatiles
• Monograph Testing
• Osmolality Analysis
• Thermal Analysis
• Total Organic Carbon (TOC)
• United States Pharmacopeia, European Pharmacopeia, Japanese Pharmacopeia

Traditionally, when medical device cleaning studies are conducted, the focus is on sterility and biocompatibility aspects, including particulate analysis, bioburden, LAL and cytotoxicity testing. The component that is often missed pertains to the effects of the manufacturing process. This includes evaluating the use of machining oils and lubricants, mold release agents, cleaning solvents and other processing aids—all of which may have a negative impact on product performance or increase patient risk.

A cleaning study should first determine what cleaning agents are utilized and then facilitate a risk assessment to determine acceptable limits of these agents. This can be difficult since many processing aids and cleaning products do not have listed components, and because purchased manufacturing parts may have proprietary constraints.

If the product is a finished device, or if a Sponsor is seeking to assess the component or product with qualitative as well as quantitative data, chemical characterization is recommended as the preferred method of testing. In this case, analyses used in an extractable chemical characterization program includes:

• Extractable Inorganic Elements by Inductively Coupled Plasma/Mass Spectroscopy (ICP/MS)
• Fourier Transform Infrared Spectroscopy (FTIR) Analysis
• Gas Chromatography (GC) Analysis for Volatiles or Semi-Volatiles
• Gravimetric Analysis using ASTM F2459 or ISO 10993-18
• Headspace Gas Chromatography/Mass Spectroscopy (HS GC/MS) for Extractable Volatile Organic Compounds
• High-Performance Liquid Chromatography (HPLC) Analysis for Non-Volatiles
• Ion Chromatography via Conductivity Detector

If a device Sponsor wishes to assess a component through a general cleaning assessment using quantitative data (not intended for a finished device), the following tests may be considered:

• Gravimetric analysis using ASTM F2459 or ISO 10993-18
• Inorganic Contamination (ICP, Ion Chromatography, Conductivity)
• Total Organic Carbon (TOC)
• Total Hydrocarbons (THC)

Independent of the testing method selected, an effective residual analysis program is essential for maintaining an acceptable level of cleanliness for medical devices. NAMSA, using a proactive approach for establishing acceptance criteria and routine monitoring, can save Sponsors time and money down the road while also ensuring medical device safety and reducing product liability.

Environmental monitoring services are performed to meet the requirements of quality system regulations when such an environment can influence the pre-sterilization bioburden testing level or resistance on a medical device.

Our medical device testing experts ensure that clients conduct the appropriate amount of sampling to suit their particular environmental monitoring needs and requirements. We not only provide you with a protocol and track your data, but also document results that will be the underlying support of your full sterility assurance program.

Common Assignments

• Airborne Particle Counts
• Bioburden
• Data handling and analysis
• Microbial Identification
• Personnel monitoring
• Surface Sampling
• Viable Air Sampling
• Water Testing

NAMSA provides best-in-class histological technology for the testing and evaluation of implanted medical devices. Valuable tissues are collected and processed on-site and under the supervision of a Board Certified Pathologist; histopathology laboratory services are also provided.

• Consultation
• Custom Sample Preparation and Sectioning
• Histochemistry Capabilities
• Necropsy Services
• Non-Decalcified and Decalcified Processing and Sectioning
• Photomicrograph Documentation
• Routine Paraffin Processing and Sectioning
• Soft and Hard Resin (Plastic) Processing and Sectioning
• State-of-the-Art Histology Laboratory
• Timely and Efficient Reporting

Exakt^® Histological System for Specialized Tissue-Implant Processing
With Exakt Histological System, NAMSA is able to process hard implants while maintaining intimate contact with surrounding tissue, while also being able to perform routine processing of soft implants in hard tissue without decalcification.

Using the Exakt System, NAMSA’s pathologists evaluate, in detail, the interface between the medical device and the cellular layer of an implant. Remarkable photographs can also be provided that are suitable for regulatory purposes and for publishing. (Note: Exakt is a Registered Trademark of Exakt Precision Tools Limited, Aberdeen, Scotland.)

State-of-the-Art Histology Laboratory
NAMSA’s state-of-the-art Histology Laboratory has the necessary tools to provide a comprehensive Pathology analysis of your study. Watch the video below as we walk through both NAMSA’s paraffin and plastic processes, including the use of our Exakt^® Histological System as described above.

Due to the integration of active pharmaceutical ingredients (API) and antimicrobial agents, more medical devices are considered to be combination products than in years past. When the stability of combination product ingredients are known, they must be tested in conjunction with the device.

The International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use provides guidelines in a streamlined effort by global regulators and researchers to outline testing requirements and ensure the safety of combination products. These testing requirements include specific temperature, humidity and duration specifications, as well as tolerances of the chambers used for the storage conditions. Typically, after subjecting a combination product to a specific condition, certain stability-indicating tests must be performed to assure potency, functionality and sterility for the intended shelf-life of the combination medical device.

Accelerated aging studies are designed to increase the rate of chemical degradation or physical change of a substance or product by using exaggerated storage conditions as part of the formal stability study. Data from these studies, in addition to long-term stability studies, can be used to assess longer-term chemical effects of non-accelerated conditions and to evaluate the effect of short-term excursions outside the label storage conditions.

Intermediate accelerated aging studies conducted at 30°C and 65% relative humidity (RH) are designed to moderately increase the rate of chemical degradation or physical changes for a substance or product intended to be stored in hotter climatic zones. Long-term studies designed to represent real-time use as required by the FDA are also available under the recommended storage conditions for the shelf life proposed (or approved) in the label claim.

We make the following stability conditions available for client programs:

• 25°C ± 2°C / 60% RH ± 5% RH
• 30°C ± 2°C / 65% RH ± 5% RH
• 40°C ± 2°C / 75% RH ± 5% RH
• 5°C ± 3°C
• –20°C ± 5°C

NAMSA also offers a variety of additional chambers for medical product shelf life and package testing needs. These chambers are available in a wider range of temperatures (from 45°C to 60°C) and humidity conditions (from ≤20% to 70% relative humidity), and provide options for aging up to the equivalent of five years’ (or more) real-time.

NAMSA offers clients clinical advisory and validation services in tandem, supported by our fully equipped R&D laboratories. This allows us to deliver Sponsors in-depth insight into testing issues and potential solutions. Areas in which our technical experts typically provide extensive assistance are within the phases of research development, validation of analytical methods and the development and characterization of new sterilization processes.

Research Development
Our R&D Teams have a proven track record with the development of successful clinical research methods and validation services utilizing the following techniques:

• Gas Chromatography (GC)
• Gas Chromatography/Mass Spectroscopy (GC/MS)
• High-Performance Liquid Chromatography (HPLC)
• High-Performance Liquid Chromatography/Mass Spectroscopy (HPLC/MS)
• Inductively Coupled Plasma (ICP) Spectroscopy
• Ultraviolet/Visible (UV/VIS) Spectroscopy

Analytical Method Development and Validation
NAMSA’s global consultants and senior scientists partner with clients to determine the appropriate analytes of interest for testing. Drawing from resources available in literature, or performing extractables profiles in our chemistry laboratory, our scientists assist clients in the determination of specific analytes of interest for your product. Methods for these analytes are then developed in the presence of your product, ensuring that sample preparation procedures are incorporated into these methods. Following, the identified method is then validated per ICH guidelines.

The studies involved in NAMSA’s validation services include: Linearity testing; precision (repeatability and intermediate precision testing); accuracy; specificity; limit of detection; limit of quantification; range; and robustness and stability of test solutions.

New Sterilization Process Development and Characterization
NAMSA’s team of experts can also assist with the development and characterization of new sterilization processes. We offer consulting services on FDA requirements for the testing required for a 510(k) submissions for any new sterilization process. With the resources in our other internal disciplines at NAMSA, we can also assist in developing biological and chemical indicators, perform testing to demonstrate that the sterilizer and sterilized materials are safe, and investigate the toxicity of any residuals. In addition, we can provide regulatory guidance on the 510(k) application, up to and including drafting the 510(k).

Packaging validation and shelf life testing are essential components of any medical device sterility assurance program. NAMSA’s suite of validation tests ensure that sterility is maintained when a device is sealed until expiration. We can assist with all testing required for materials, equipment and process qualification.

Services include, but are not limited to:

• Accelerated Aging (ASTM F1980 and AAMI TIR 17)
• Barrier Properties (ASTM F1608)
• Biocompatibility (ASTM F2475)
• Burst Testing (ASTM F1140)
• Complete Package Validation with Protocol and Final Summary Report
• Dye Penetration (ASTM F 1929)
• Dye Penetration of a Vial
• Gross Leak Test (ASTM F2096)
• Gurley Porosity Testing
• Liquid Microbial Immersion
• Packaging Conditioning
• Real-Time Aging (ICH and Room Temperature Conditions)
• Sampling Plans
• Seal Tensile Strength (ASTM F88)
• Shipping Simulation (ASTM D4169, D7386 and ISTA or custom programs)
• Vacuum Leak Bubble Emission (ASTM D3078)
• Visual Inspection (ASTM F1886)

NAMSA performs medical device particulates testing on injections, parenteral infusions and medical devices as particulate matter is produced through various sources during processing. Since there is no single method for testing parenteral products or medical devices when conducting particulate analysis, our teams consider how manufacturing, sterilization, shipping and distribution, packaging, shelf storage, and use with other devices affect the particulate levels of a medical device. NAMSA prepares a test specification for every sample, typically established prior to sample arrival, and adheres to AAMI/TIR 42, Evaluation Particulates Associated with Vascular Medical Devices.

Methods
For injectable (parenteral) products, particulates testing is performed according to USP procedures, unless otherwise specified. In the case of medical devices, the solution is analyzed for particulate matter according to USP procedures unless otherwise specified. NAMSA also offers personalized procedure particulate tests (i.e. ISO, EP, JP).

According to USP <788> Injections and <789> Ophthalmic Solutions, the Light Obscuration Method and the Microscopic Method are the preferred approaches to analyze particulate matter.

Light Obscuration Method: This method analyzes the device rinse solution or injectable product using a light obscuration particulate analyzer. Four (4) 5 ml portions of the extract are analyzed by the instrument; the data from the first count is discarded. The second through fourth count is averaged and then compensated for the entire extract (or reported in particles per ml.). The advantage to this method is that it is a quick and easy process to count particulate, and it can count high amounts of particulate in the solution. A minimum of 25 mL of solution is required to perform this method.

Microscopic Method: This method filters the device rinse solution or injectable product through a 0.8 μm grey gridded filter. The filter is then counted microscopically at 100x to determine the number of particles, counting particles in the entire test solution.

The data from the Microscopic Method tends to be lower, so the pharmacopoeia makes up for the difference by having lower limits for the microscopic method. Both methods count particles greater than 10 μm and greater than 25 μm (and greater than 50 μm for USP <789> Ophthalmic Solutions.). Note that other sizes may be counted upon request.

Since procedures for testing medical devices are not covered in the USP, it is at the Sponsor’s discretion to determine the method of testing and the procedure to remove a particulate from the device.

Identification

The identity of particulates and potential source of matter may also be an important consideration when investigating or characterizing particulate matter on a medical device. It may be critical to the development process to consider the identity, source and potential toxicity of each type of particulate as well as the sizes, shapes and quantities of particulates. It is not expected that all particles require identification, but efforts should be undertaken when appropriate (e.g., when particulate levels have exceeded limits and as necessary to better derive the source of particles).

With unparalleled experience and scientifically-trained teams, NAMSA offers the most complete physician training solutions in the CRO industry. We understand the importance of the relationship between device manufacturers and health care professionals and its criticality to the development of innovative technologies and products.

NAMSA’s physician training locations offer an environment where meaningful interactions occur surrounding device testing and training, ensuring the delivery of safe and effective products and gathering physician feedback. After all, physicians play one of the most critical roles in determining which medical devices are utilized in the treatment of their patients.

NAMSA offers clients an accessible and adaptable research and training laboratory designed to facilitate a wide range of scientific needs. Each client that partners with NAMSA for physician training solutions benefits from the following:

• Advanced imaging and video services:

– Acuson Cypress Ultrasound
– ADI PowerLab System
– Bard Lab System Pro Electrophysiology Station
– Digital video capture, recording in ORs and live webcasting
– DNTLWorks ProCart II Mobile Dental Treatment Console
– DSI System with updated Ponemah Software
– Fresenius Dialysis Machines
– Milestone Med MacroVIEW Digital Imaging System and Quantitative Analysis Software
– Moller-Wedel Surgical Microscopes
– Philips BV Pulsera Fluoroscopy with CT
– Progeny Digital Dental X-Ray
– Stryker Lap/Endo Tower
– QCA
– Volcano IVUS

• Domestic and International Travel Capabilities
• In Vivo Anatomical Model
• Pathology Services
• Sizable Classrooms for Dry/Wet Labs and Surgical Suites

NAMSA is proud to offer preclinical, interventional and surgical study capabilities in a range of locations across the globe. Working in our state-of-the-art laboratories, NAMSA’s highly-trained experts utilize a broad range of trusted In Vivo models and analysis tools, including 4 Siemens Cath Labs and a 128-slice CT Scanner, among other advanced technologies, to deliver study results in an accelerated, cost-efficient manner. We also understand the criticality of complying with methods and regulations within the European Committee for Standardization (CEN), U.S. Food and Drug Administration (FDA) and other international guidelines to provide Sponsors with the most reliable, accurate outcomes in industry.

Combining decades of experience in therapy delivery systems and implantable medical device research, NAMSA has the distinction of serving as the industry’s premier destination for preclinical research. Some of our most requested areas of study, include:

• Cadaveric Non-Clinical Testing
• Cardiac Surgery
• Coronary and Peripheral
• Dental
• Dermal Wound Healing
• Drug Coated Balloons
• Electrophysiology
• Embolization Devices
• Endoscopy
• Gastrointestinal and Urogenital
• Heart Valves
• Neuromodulation
• Orthopedic and Bone Healing
• Physician Training
• Pulmonary Therapies
• Specialty Pathology Services
• Stents/Graft
• Tissue Engineering
• Transcatheter and Surgical
• Thrombogenicity Testing

Medical device sterilization validation studies are performed for all processes, including radiation sterilization by either gamma radiation or electron beam, ethylene oxide gas sterilization, hydrogen peroxide sterilization and thermal sterilization (both moist and dry heat).

At NAMSA, we’re known for our ability to design custom protocols that not only meet clients’ testing budgets, but are also backed by a complete documentation package that fulfills all necessary regulatory requirements.

Tests offered by NAMSA include:

• Bacteriostasis/Fungistasis Testing
• Bioburden Testing
• Biological Indicator Sterility Testing
• Dose Audits Testing
• Dose Verification Experiment Testing
• EO Cycle Development Testing
• EO Residual Testing
• Fractional Cycle Study Testing
• Growth Promotion Testing
• Half-Cycle Study Testing
• Monitor/Notification of Quarterly Testing
• Pharmacopoeia Sterility Testing

Reusable medical devices have been employed in healthcare facilities for more than a century, but today’s designs are more complex and sophisticated than in years past. This makes the process of cleaning, disinfecting, and sterilizing reusable devices very involved in order to ensure safety to the end user.

Proving sterilization validation or disinfection efficacy is only part of the equation; other issues related to medical device function, physical integrity, and biocompatibility testing must also be addressed. Reusable products must be designed to function safely and effectively following sterilization in a healthcare setting, and to withstand multiple exposures to sterilants or disinfectants without losing their ability to function effectively.

Testing should not be limited to the efficacy of the sterilization cycle; biocompatibility and functional performance of the medical device should be considered as well. This can be accomplished by exposing a product to multiple cycles equivalent to the projected maximum useful life of the device, including any cleaning steps performed between cycles. Following these exposures, functionality, physical integrity, and biocompatibility should be demonstrated through adequate testing.

NAMSA conducts studies as recommended in AAMI TIR 12 (sterilization efficacy testing) to provide data to demonstrate each product’s recommended instructions provide an equivalent sterility assurance level of 10^–6. Services range from Disinfection Validation, Cleaning Studies and Repeat Sterilization Cycles.

NAMSA’s world-class clinical research organization (CRO) testing capabilities include all areas of microbiological quality assurance. Our well-equipped facilities contain laboratories for bacteriology and sterility testing, clean rooms, aging chambers and media preparation areas. Beyond sterility assurance programs, we also offer the following services to clients worldwide:

• Antimicrobial Testing
• Bacterial Endotoxin (LAL)
• Cleaning Efficacy Studies
• Comparative Resistance Studies
• Microbial Identification
  • Genotypic/MicroSEQ^®
• Microbiological Examination of Non-Sterile Products, USP <61> and USP <62>
• Product Inoculation Testing
• Raw Material Bioburden
• Reusable Device Studies (cleaning, disinfection and sterilization)
• Surface Disinfection Studies
• Test Development
• Validation of Microbial Recovery