Materials Characterization and Analytical Chemistry

Ethylene Oxide, Ethylene Chlorohydrin and Ethylene Glycol Analysis

When medical devices are sterilized with ethylene oxide gas, the gas may leave behind residuals of ethylene oxide (EO), Ethylene Chlorohydrin (ECH) and Ethylene Glycol (EG) on the product.  Ethylene chlorohydrin and Ethylene Glycol are formed when ethylene oxide comes in contact with chlorine and water, respectively.  There are a variety of procedures for determining the amount of residual Ethylene Oxide (EO) present in medical devices and materials.  Methods performed are based on ISO 10993-7, although in this document, the analysis of Ethylene Glycol is no longer required.

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pH Determination

The pH of a solution is measured on a scale of 0 to 14.  When the pH is less than 7, the solution is considered acidic, while those with a pH greater than 7 are considered basic (alkaline).  A bench top pH meter is used to perform this testing. 

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USP <661> testing

Physicochemical testing

Designed to determine physical and chemical properties of plastics and their extracts, these tests in USP <661> are based on the extraction of the plastic material.  It is essential that the designated amount of the plastic be used. Also, the specified surface area must be available for extraction at the designated temperature.  Only water is used in this extraction process.

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Physicochemical Testing, Alternate Solvent

Designed to determine physical and chemical properties of plastics and their extracts, these tests are based on the those USP <661>, however an alternate solvent is used, so no limits are provided

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USP Polyethylene Container Testing

These standards in USP <661> are designed to test containers and components used to package medical articles (pharmaceuticals, biologics, dietary supplements, and devices), produced from either low-density polyethylene or high-density polyethylene of either homopolymer or copolymer resins.   

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USP Polyethylene Terephthalate Bottle Testing

These standards in USP <661> are designed to test containers and components used to package medical articles (pharmaceuticals, biologics, dietary supplements, and devices), made from polyethylene terephthalate (PET) and polyethylene terephthalate G (PETG).

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USP Polypropylene Container Testing

These standards in USP <661> are designed to test containers and components used to package medical articles (pharmaceuticals, biologics, dietary supplements, and devices), produced from either low-density polypropylene or high-density polypropylene of either homopolymer or copolymer resins.   

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Fourier Transform Infrared Spectroscopy

Provides a fingerprint of a material by passing infrared radiation through the test article. This can be used for confirmation of the identification of known materials, or to identify an unknown material.  This procedure can be used on test articles, extracts of the test article, or in conjunction with a microscope to identify small particles and contaminants.

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Particulate Analysis

Based on USP <788>, used to count particles with sizes between 10 mm and 25 mm.  This can be performed on a device by rinsing the test article with high purity water and counting the particles found in the wash, or on a solution.  There are two methods available; light obscuration in which particles are passed through a detector and counted based on the blockage of light; or microscopic, in which the solution is filtered and particles are counted manually.

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Gas Chromatography

An analysis technique in which a sample is vaporized and injected onto the head of the chromatographic column.  It is useful for extractables with lower molecular weight and lower boiling points (<300°C). A variety of detectors may be used including Flame Ionization, Mass Spectrometry and Headspace.

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Liquid Chromatography

High Performance Liquid Chromatography (HPLC) covers a broad range of analytical techniques that use a liquid mobile phase to analyze for non-volatile, larger molecular weight compounds.

A variety of detectors and separation techniques are available including, UV/Vis, Refractive Index, Mass Spectrometry, Quadrapole Time of Flight (QToF), Gel Permeation (for molecular weight analysis), and Ion Chromatography (for analysis of cations and anions).

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Hardness Testing

Test used to measure the resistance of plastics toward indentation and provide an empirical hardness. Shore Hardness, using either the Shore A or Shore D scale, is the preferred method for rubbers/elastomers and is also commonly used for 'softer' plastics such as polyolefins, fluoropolymers, and vinyls. The Shore A scale is used for 'softer' rubbers while the Shore D scale is used for 'harder' ones.

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Ultraviolet/Visible Scan

The UV/Vis test measures the amount of UV/Visible light transmitted or absorbed by either from a test article or a test article extract.  In the case of a plastic or glass material it can be an indication of the ability to protect the product.  In the case of an extract, it can be an indication of the extractables present.

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Heavy Metals Testing per United State Pharmacopeia (USP)

This test is provided to demonstrate that the content of metallic impurities that are colored by sulfide ion, under the specified test conditions, does not exceed the Heavy metals limit specified in the individual monograph in percentage (by weight) of lead in the test substance. Substances that typically will respond to this test are lead, mercury, bismuth, arsenic, antimony, tin, cadmium, silver, copper, and molybdenum.  The test can be conducted on water soluble materials, or those that can be brought into solution by acid digestion.

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Melting Point Determination

Determination of the temperature at which a solid becomes a liquid.  Differential Scanning Calorimetry (DSC) can also be used to determine phase shifts, glass transition temperatures, and crystallization temperatures.

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Refractive Index Determination

Specific Gravity

The ratio of a substance's density compared to a reference (generally water's) density

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Aging Studies

Chambers available at a variety of temperatures and humidities to simulate aging of test articles at real or accelerated times to study long term effects.  Aging Chambers are available for Package testing, and Medical Devices. General chambers are available,  as well as those set to those temperatures specifically outlined in the guidance document for the International Conference on Harmonisation for drug products, antimicrobials and other medical device testing needs.

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USP Sterile Purified Water

Procedure for determining the chemical purity of water samples obtained by distillation, ion-exchange treatment, reverse osmosis, or other suitable process.  These tests are designed to confirm compliance to specification found in the USP chapters on Sterile Water.

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Package Testing

Mechanical testing instrument used to measure stress and strain of medical device materials and packages.  Tensile properties such as load, stress, strain and Young’s modulus, can be evaluated.  Peel strength and compression can also be determined.

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Japanese Pharmacopeia Monograph Testing

This test code can be used to follow the Japanese Pharmacopeia for any test method that does not have its own unique test code.

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Osmolarity/Osmolality Determination

Used to determine osmotic concentration of biological fluids by freezing point depression.

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ASTM Glove Leakage Testing

Procedure to determine acceptance or rejection of latex examination and surgical gloves as determined by Watertight test

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European Pharmacopeia Monograph Testing

This test code can be used to follow the European Pharmacopeia for any test method that does not have its own unique test code

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Inductively Coupled Plasma Spectroscopy

Inductively Coupled Plasma (ICP) Spectroscopy is a quantitative technique for analyzing metals and elements in a device or in an extract from a device.  It is an emission spectroscopy technique that uses plasma to produce excited atoms and ions, which emit electromagnetic radiation at wavelengths characteristic of particular elements.  The intensity of the reading is indicative of the concentration. This technique can provide detection levels at the part per billion level.

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United States Pharmacopeia Monograph Testing

This test code can be used to follow the United States Pharmacopeia for any test method that does not have its own unique test code

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USP Purified Water Testing

Procedure for determining the chemical purity of water intended for use as ingredient water and is prepared by distillation, ion-exchange treatment, reverse osmosis, or other suitable process.  Purified Water is not meant to be used for preparations intended for parenteral preparations.  Total Organic Carbon (TOC) analysis measure the organic molecules present in water.

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Japanese Pharmacopeia Test Methods for Plastic Containers

Test methods for design and quality assurance of test containers as outlined in JP 7.02

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EP Section 3.1.8, Silicone Oil used as a Lubricant, Monograph Testing

Identification section of 3.1.8, Silicone Oil used as a Lubricant

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EP Section 3.2.1, Glass Containers for Pharmaceutical Use Monograph Testing

Test Methods for Glass Containers for Pharmaceutical Use

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EP Section 3.2.9/ USP <381> Monograph Testing

Harmonized Test procedure for rubber closures intended for use in injectables

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USP Glass Container Testing, <660>

Glass Container testing as outlined in USP <670>.  Glass used for pharmaceutical containers is either a borosilicate (neutral) glass or a soda-lime glass.

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JP Test for Rubber Closure for Aqueous Infusions

Test methods for rubber stoppers that are in direct contact with an aqueous solution, on a container 100 ml or larger in size, as outlined in JP 7.03

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USP Arsenic Analysis, Method I

Designed to determine the presence of trace amounts of arsenic (As) by converting the arsenic in a substance under test to arsine, which is then passed through a solution of silver diethyldithiocarbamate to form a red complex.  Method I is used for inorganic materials.

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External Standards Testing

Any test method where work instructions are provided by a standard method such as ISO, ASTM EN, etc.

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Japanese MHLW Extraction process

Procedure are available, for performing a preliminary and exaggerated extractions.  The preliminary extraction is performed on a test article to determine the most suitable extraction method for genotoxicity or sensitization testing.  Based on the results, the appropriate method is chosen for the exaggerated extraction process for the definite studies.  Method 1 requires 1 gram of residue to be produced from the test article. Method II requires 15 grams of residue for Induction I and 10 grams of residue for Induction II and Challenge Phase, to be produced from the test article.

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Exhaustive Extraction

Exhaustive extractions are primarily designed for materials characterization, especially in the case of permanent use or drug delivery devices.  Samples are heated multiple times until >90% of all extractables are removed.  This determination is made gravimetrical (by weight) using the total non-volatile residue from each extraction time point.  The time points and temperatures to extract at are based on the materials stability.

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USP <671>, Containers, Light Transmission

Determination of the amount of light transmitted through a glass or plastic container

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