FDA Fees for Device Makers to Double

Medical device makers have tentatively agreed to have FDA review fees doubled starting this year. The current five year agreement, set to expire on September 30, 2012, is set at $287 million.  If the new deal is signed off by Congress, the FDA is set to receive $595 million in user-fees over the next five years.  As a result, there will be reductions in total review times, a greater number of pre-market and 510(k) approvals, and more communication with companies during the review process.  The agreement will also require FDA reviewers to meet with the applicants halfway through the process to make sure any concerns are addressed and that goals are being met.

There has been criticism from the industry in the past few years on slow approval times, and last minute safety data requests that can cost companies a lot of money.  This can hinder innovation because the process has become so cumbersome and unexpected costs make it unpredictable.  Even with this proposed increase, medical device companies will still be paying a smaller portion of the FDA’s review budget.  Drug companies currently pay about 60%, while device companies will be paying about 35% of the budget after the increase.

If you would like to learn more about how to plan for biocompatibility testing, and for detailed information on ISO and FDA regulations for medical devices, download the 26-page booklet on Assessing Biocompatibility.

Learn About the Types of Biocompatibility Tests

Biocompatibility testing measures how compatible a device or material is with a biological system, and is needed to begin human trials of a medical device. Biocompatibility testing can provide an initial screening of whether the components of a medical device may cause adverse effects when interacting with the human body.

Initial Screening and In Vitro Testing

Usually, testing begins with the characterization and analysis of the components of a device. The device is submerged in extraction media under specified conditions to evaluate whether anything that leeches out from the device materials can be potentially harmful or toxic. Additional tests for cytotoxicity can be done to check for effects on tissue cultures before in vivo testing is done. This is done by placing the test article or an extract of the material onto cells to see whether there are any adverse effects. The viability of cells can also be measured by spectrophotometric methods or by counting the number of colonies formed after exposure to the test material.

Sensitization Assays

Various types of in vivo testing exist and are often required by federal agencies for approval of a device depending on its intended use. Sensitization studies tell us whether or not the device contains chemicals that can cause an adverse local or systemic effect after prolonged exposure. It screens for substances that would cause an allergic reaction in humans. Types of sensitization assays include the Guinea Pig Maximization Test, the Closed Patch Test, and the Murine Local Lymph Node Assay. Irritation studies evaluate local irritation on skin and mucus membranes. These include Intracutaneous, Primary Skin Irritation, and Mucous Membrane Irritation tests, which are performed depending on the route of exposure and duration of contact of the intended device.

Toxicity Testing

Systemic toxicity tests involve testing extracts of the device to evaluate whether leachables from the device produce toxic effects. Acute toxicity results in an immediate reaction after an exposure (<24 hours) and also evaluates the potential of materials to cause a pyrogenic, or feverish, effect. Subacute toxicity evaluates products with prolonged (24 hours to 30 days) exposure, while subchronic and chronic toxicity measures results for long term to permanent devices over several weeks or months. Implantation tests are often performed in addition to the previously mentioned tests for devices that will come in contact with living tissue other than skin. After the appropriate time has passed, histopathological examination must be done. Tissue from the surrounding area of the implant is examined for adverse reactions.

Genotoxicity, Hemocompatibility, and Carcinogenesis

Genotoxicity testing evaluates whether a certain material has the potential to affect the integrity of DNA by making it mutagenic or cancerogenic. Hemocompatibility tests range from hemolysis to coagulation to prothrombin time assays and is assessed for devices which will come into contact with blood. It is an evaluation of the amount of damage a device or material can cause to red blood cells. Depending on the intended use and placement of the device, carcinogenesis bioassays and pharmacokinetic studies may also be needed.

Many of these tests are done in-house at our facility in Hercules, CA but some of them are subcontracted as needed. The chart below lists which tests are done in house and which ones are subcontracted (for more information and a list of services provided visit http://www.pacificbiolabs.com/testing_services.asp)

Pacific BioLabs Toxicologist awarded DABT

Pacific BioLabs is proud to announce that we now have a certified PhD Diplomate of the American Board of Toxicology on staff. He recently was awarded this pretigous distinction from the world's premier certifying body for toxicology competency.

More than 20% of the staff members of Pacific BioLabs' Toxicology Department are PhDs, and we are happy to continue to be able to offer a high level of expertise to our valued clients.

Happy New Year and here's to a fantastic 2012!

Keys to a Successful Environmental Monitoring Program

Why is an effective environmental monitoring program so important?

In the end, whether you are manufacturing a medical device or a drug API, the safety of end users is at stake. Having a thorough environmental monitoring program in place will allow you to know the status of your environment, giving you the power to control it and make changes to it.

The overall keys to implementing an environmental monitoring program

1. Determine what the monitoring strategy will be, including:

  • Limits and acceptance levels (often based on the product being manufactured and knowledge of your facility)
  • Decide what specifically should be monitored
  • Determine the frequency of monitoring
  • Identify where problem areas might be; note where limits are most likely to be challenged

2. Decide on the type of sampling necessary:

  •  Air – good for general environment, but be aware that air contamination is affected by levels of activity
  •  Surfaces – products may come into contact with surfaces so surface collection strips may be necessary

3. Implement a thorough documentation procedure – data must match procedures

4. Must validate the monitoring procedure and ensure that collection media and techniques are sufficient

5. If any change in the manufacturing process or area occurs then you must decide whether monitoring changes need to be implemented. Also, if results have been steady for a long period of time, the frequency of testing may possibly be reduced

6. Use the results of the data to determine whether changes can be implemented to minimize the possibility of contamination

These are just some of the basic keys to implementing a successful program. For a more thorough background, we recommend "Environmental Monitoring: Making the Invisible Environment Visible" in Contract Pharma magazine.

A Background on Radiolabeled ADME

ADME studies are used to look at how drugs are processed by the body. Essentially, they measure how a drug makes its way throughout the body, how the drug is metabolized or inactivated, and how the body gets rid of the active and inactive metabolites.

A powerful way to measure this is through the use of radiolabeled compounds. By adding a radioactive isotope such as tritium or carbon-14 to a drug candidate, it is possible to accurately measure the amount of compound within plasma, urine, feces, and bile. ADME studies are not just important in drug development; they are required because they directly relate to human safety evaluations. By looking at exposures in testing species and comparing metabolites in animals and humans, it becomes possible to validate the choice of species for toxicology studies.

One important consideration in radiolabeled studies is the use of isotope. The radiolabeling process can be intensive depending on the choice of isotope. For instance, it is frequently easier to label compounds with tritium than C-14 because hydrogen atoms are more accessible for replacement, whereas substituting a carbon atom within a coumpound can require more complex chemistry. Additionally, the location of the radiolabeling is important - if the label is on a part of the compound that is cleaved off during first pass metabolism, recovery of radiolabeled compound can be altered.

These are just a few considerations when constructing a radiolabeled ADME program. If you are in the process of constructing an ADME program, PBL may be able to assist you with more information about our radiolabeled ADME testing services.

Uses of Botulinum Toxin and Botulinum Toxin Testing

What are Botulinum Toxins?    

Botulinum toxins are produced by the bacterium Clostridium botulinum and are perhaps the most poisonous natural toxins known.  Ingestion of the toxin results in rapid neurotoxicity, leading to paralysis through disruption of neuronal function. Interestingly, the toxin’s paralytic action is being exploited for cosmetic and therapeutic applications. The toxin can be delivered safely in very small doses to treat a variety of conditions including Crow’s Lines, involuntary eye muscle contractions (blepharospasm), cervical dystonia, and migraines. Current unlicensed indications include low back pain, Parkinson’s disease, and chronic anal fissures.

Botulinum Potency Testing

Every therapeutic preparation of botulinum toxin is required by the FDA to be tested for potency and stability during the production process. This testing is required to determine if the product is suitable for release to the clinic. Both the active pharmaceutical ingredient (Drug Substance) and the final formulated product (Drug Product) must be tested for potency and stability.                 

In addition to stability and potency testing, patients treated with botulinum toxin may develop antibodies that make the toxin ineffective. Clinicians need to verify if the patient has produced antibodies to botulinum toxin in order to determine if a patient will respond to treatment. The assay uses patient serum mixed with toxin. If the patient has developed antibodies to the toxin, the toxin’s effect will be decreased. If the patient does not have antibodies to the toxin, the toxin will remain fully active.

Pacific BioLabs has a dedicated staff with expertise in toxin testing for stability and potency determinations of drug substance and drug product. PBL staff can also test patients’ serum for the presence of anti-botulinum toxin antibodies. Experienced study directors and technical staff can assist in the design and execution of studies, and provide a rapid turnaround time for results. 

Why You Should be Using the MTT to test Cytotoxicity

Until recently, the only methods available to measure cytotoxicity were qualitative ones. These methods are subjective and rely on the skill of a microbiologist to identify malformed or lysed cells. Based on what the operator sees in the microscope, a determination of whether or not a material is cytotoxic is made.

The most recent revision of ISO 10993 (Biological Evaluation of Medical Devices), describes quantitative methods for cytotoxicity testing. ISO 10993-5:2009 states that while qualitative cytotoxicity methods are useful for screening purposes, quantitative cytotoxicity methods are now preferred for determining material cytotoxicity.

Annex C of ISO 10993-5 refers to the MTT assay as a prescribed quantitative cytotoxicity method. The MTT has several benefits over traditional qualitative cytotoxicity methods. It can accurately measure as few as 950 cells, it can be performed on material extracts or through direct contact, and the results are not subjective, increasing repeatability. Additionally, the MTT is a colorimetric assay and as such a standard microplate reader can be used to analyze the results, increasing throughput ability.

Pacific BioLabs has recently introduced the MTT Assay as an available test method, and the results have been very positive. The sensitivity of the assay, coupled with objective readings, provide study sponsors with greater information and increased confidence in the results. Therefore, we recommend quantitative assays such as the MTT for all final cytotoxicity data purposes.

Biotech, Medical Device, and Regulatory News - August 5, 2011

Biotech and Medical Device Weekly Roundup July 15, 2011

Life Science Roundup July 1, 2011

Biotech and Medical Device Weekly Roundup 6-24-2011

Some of the most thought-provoking stories of the week:

Electronics Manufacturers and Oil Companies Race to Hop on Biosimilar Wagon - Reuters

U. S. Supreme Court Rules to Protect Generics Makers - CBS News

Researchers Develop Novel Nanotech Particles to Battle Cancer - North County Times

Slowdown in FDA Medical Device Approval Rates - Mass Device

Finally, two articles on Big Pharma giants leaving a device industry:

AstraZeneca Sells Med Device Unit - Boston Business Journal

Johnson and Johnson Leaves the Stent Market it Created - Med City news

Biotech Weekly Roundup 6-10-2011

Strategies for Preclinical Outsourcing in 2011

When choosing and working with preclinical CROs, what are the key factors that should influence your selection? A recent article, “Smart Moves for 2011,” written by Steve Snyder for the March 2011 issue of Contract Pharma, answers that exact question. The article lists several ways in which sponsors can improve their relationships with, and the quality of work from contract research organizations. Here are some of our favorite tips:

1.       Check the regulatory status, quality history, and accreditations of CROs. There are several questions you may want to ask yourself before selecting a CRO: Will your testing be performed according to GLP regulations? What is the history of the CRO with the FDA? If inspections have resulted in a form 483 issuance what was the reason, and has it been adequately addressed? Depending on your studies, you may even want to speak with the management team regarding quality control. Additionally, you may want to look at the responsiveness of the CRO to any client dissatisfactions that may have occurred in the past.

2.       Provide accurate information when requesting study quotes. CROs, like any company, do their best to estimate business and plan personnel and capacity levels based on expected activity levels. If, as a company, you schedule studies with CROs and then cancel them, it can negatively impact the CROs ability to plan and to handle your business in the future. If you are requesting information for planning purposes only, let the CRO know. Most will still be happy to provide you with costs and information on the chance that they can secure your business at some point in the future.

3.       Be wary of very low prices. This almost goes without saying, but if one price comes in substantially lower than all other bids, there may be something the CRO isn’t telling you. Be sure to ask about past experience with the study type, and compare testing lists from one quote to another to make sure that the lowest cost bid isn’t cutting corners that might negatively impact you later on when it’s time to file an IND or other regulatory submission. Sometimes money saved in the preclinical phase can end up costing you much more later.

4.       Personnel. Have there been significant personnel changes within the CRO? If experienced personnel have moved on, the knowledge necessary to carry out your testing to the highest standards may have left as well. It’s worth performing a little investigation to make sure your project will be completed the right way.

5.       Get your test article to the CRO on time. Study sponsors expect their testing to begin on time, and to finish on time. Yet, some of those same sponsors have been known to delay shipment of samples, which can put an entire study off course from the onset. Many studies, especially complex ones, require a high level of coordination to execute. Key personnel need to be scheduled, space needs to be reserved, and in many cases animals need to be purchased. Late arriving samples can put this entire process in jeopardy. Give your study the best possible chance for success and ship your samples on time.

These are just a few points out of many that the articles lists. The full text is excellent and is definitely recommended reading for anyone looking into new outsources testing services. You can find it here: http://www.contractpharma.com/articles/2011/03/preclinical-outsourcing

 

An Overview of Microbial QC Test Procedures

Why Is Microbial Testing Necessary?

“How do we determine that our substance or preparation complies with an established specification for microbial quality?” This is what many manufacturers or producers of pharmaceuticals or medical grade products ask themselves. When manufacturing a product for human use or consumption, there are many considerations involved, not least of which is proving that the product or sample is safe for use, and determining how long the product can stay safe without changing its original composition or nature. Much of this centers on ensuring that microbial contamination is within established limits and standards.

History of the Harmonized MLT

To be able to determine whether a substance, a product, or a preparation complies with an established specification for microbial quality, testing needs to be performed. Many standards have been created not only to guard the manner of production but ultimately protect consumers and avoid release of a product that is unsafe to use. Historically, the United States Pharmacopeia chapter <61> Microbial Limits Test, provided directives for the estimation of the numbers of viable aerobic microorganisms present in a manufactured nonsterile product. It contained instructions to perform testing for: Plate Count (TPC), which includes Aerobic Plate Count (APC) and Yeast/Mold Count (YMC), and Screening/ Detection for Specified Microorganisms. USP Chapter 61 was also equivalent to Chapter 35 “Microbial Limit Test (MLT)” of the Japanese Pharmacopoeia.

In order to provide for standards that are applicable not just in the United States, but around the world, and because certain chapters from the USP are nearly identical to sections of the European Pharmacopeia, a course of harmonization was decided upon. International harmonization of the chapters was initiated and made official by the USP on May 1, 2009. The previous version of the MLT, USP <61>, was separated into 2 chapters, USP chapter <61> Microbial Enumeration Tests (MET) which includes Total Aerobic Microbial count (TAMC) and Total combined Yeasts and Molds Count (TYMC); and USP chapter <62> Tests for Specified Microorganisms. These chapters are equivalent to European Pharmacopoeia (EP) chapters 2.6.12 Total Viable Aerobic Count (TAC) and 2.6.13 Tests for Specified Microorganism. Incidentally, these chapters are exactly identical to the British Pharmacopoeia (BP) chapter B1. Tests for Specified Microorganisms and B2. Total Viable Aerobic Count.  Because of these equivalencies, the new USP Chapters are commonly referred to as the “Harmonized MLT” or the “Harmonized Microbial Limits Test.”

Microbial Testing Procedures for Manufactured Products

Microbial Limits Testing must be carried out under conditions designed to avoid accidental extrinsic microbial contamination of the product to be examined during the test. However, any product/preparation with antimicrobial component(s) needs to be neutralized to remove its antimicrobial activity before testing. The validity of the test results depends largely upon demonstrating that the test articles do not inhibit the multiplication of microorganisms that may be present under any test condition.

Classification of product plays an important role in the selection of the test method (Plate Count Method, Most-Probable-Number (MPN), and Membrane Filtration), type of organisms that need to be screened, and acceptance criteria to be imposed according to the microbial quality prescribed by the standards. Before any testing to occur, Growth Promotion, Suitability of the Counting Method (Validation), and Suitability Tests for Specified Microorganisms (Validation) should be performed first. The ability of the test to detect microorganisms in the presence of the product to be tested must be established, and suitability must be confirmed if a change in testing performance or a change in the product is introduced that may affect the outcome of the test.

Antimicrobial Preservatives and Testing Considerations

Products may contain antimicrobial preservatives added to prevent proliferation or limit microbial contamination that may occur subsequent to the manufacturing process. Preservatives may also be added to inhibit the growth of microorganisms during normal conditions of storage and use, such as when microbes might be introduced inadvertently from repeated withdrawing of individual doses of a product from a containment vessel. Without preservatives, continued use could results in spoilage of the product or render it hazardous to users. Always keep in mind, however, that “Antimicrobial preservatives must not be used as a substitute for Good Manufacturing Practice.”

In order to support a claim that the added preservative is adequate to provide protection from adverse effects that may arise from microbial contamination or proliferation of microorganisms during storage and use, the USP Antimicrobial Effectiveness Test (AET), also known as Efficacy of Antimicrobial Preservation (EAP) - European (EP) and British Pharmacopoeia (BP) and Preservatives-Effectiveness Tests (PET)-Japan Pharmacopoeia (JP) should be tested to. This test is not intended to be used for routine control purposes, but instead is focused on challenging the preparation in its final container with prescribed inoculums of suitable microorganisms.

Compendial articles for testing have been divided into four categories based on route of administration. Each category has its own acceptable criteria for tested microorganisms. Individual product samples are inoculated with high concentrations of specific organisms and incubated at room temperature for 28 days. The population of any surviving microorganisms will be determined at a specific time interval depending on which standard is to be followed (each standard has its own intervals). Determination of the surviving microbial population will be performed using the Plate Count Method and calculating the log reduction of each microbial strain. However, prior to performing the actual test, a Plate Count Method Validation must be completed for the specified item.

Summary

The first step to successfully test any product is to know the product itself, and be able to classify it according to its intended final use. The nature and frequency of testing vary according to the products, as some may require freedom from one or more species of selected indicator microorganisms.  The significance of microorganisms in non-sterile pharmaceutical products should be evaluated in terms of the use and the nature of the product, and the potential hazard to the user as well. Certain categories of products should be tested routinely for total microbial count and for a specified indicator of microbial contaminants. Regardless, it is still essential to apply strict good manufacturing practices to assure the lowest possible load of microorganisms. For reliable results, testing should be performed by personnel with specialized training in Microbiology and in the interpretation of microbiological results and data. 

Pacific BioLabs can provide you with USP <61> and <62> Microbial QC Testing Services, including microbial limits testing, antimicrobial effectiveness testing, and microbial enumeration.

References:

USP Chapter <61> http://www.usp.org/pdf/EN/USPNF/generalChapter61.pdf

USP Chapter <62> http://www.usp.org/pdf/EN/USPNF/generalChapter62.pdf

USP FAQ on chapter 61: http://www.usp.org/USPNF/pharmacopeialHarmonization/genChapter61FAQ.html

USP FAQ on chapter 62: http://www.usp.org/USPNF/pharmacopeialHarmonization/genChapter62FAQ.html 

The Key Concepts of Biocompatibility Testing

*The following article is the Executive Summary from the booklet "Assessing Biocompatibility: A Guide for Medical Device Manufacturers"

Purpose of Biocompatibility Testing

Biocompatibility is, by definition, a measurement of how compatible a device is with a biological system. The purpose of performing biocompatibility testing is to determine the fitness of a device for human use, and to see whether use of the device can have any potentially harmful physiological effects. As stated by the International Organization of Standards:

“The primary aim of this part of ISO 10993 is the protection of humans from potential biological risks arising from the use of medical devices.” (ISO 10993-1:2009)

The overall process of determining the biocompatibility of any medical device involves several stages. One should begin by collecting data on the materials comprising the device, then perform in vitro screening (often only on components of the device), and finally conduct confirmatory in vivo testing on the finished device. It is essential to make sure that the finished device is challenged to ensure that human use of the device does not result in any harmful effects.

Biocompatibility Test Planning

The primary goal of a biocompatibility screening program is the protection of humans. However, since animal testing is necessary for many biocompatibility tests, a secondary goal is to eliminate unnecessary testing and minimize the number and exposure of test animals. With this in mind, it is important to conduct research beforehand to document all relevant data on the component materials of the device and on similar devices with an established clinical history. Existing data may be sufficient to demonstrate biological safety of parts or of the entire device, thus precluding the need to conduct certain tests.

The required tests will also depend on the use of the device and the manner and duration in which it will interact with the body. In test planning it is important to note whether the device is a surface device, an external communicating device, or an implant device, and what tissues the device will contact. (Implant devices interacting with the blood, for instance, will require more thorough testing than a surface device with an expected contact time of only a few days.)

When planning, it is also important to note that Good Laboratory Practice (GLP) compliance is required for certain biocompatibility regulatory submissions. Because of this, it is generally a good idea to conduct biocompatibility testing according to GLP to allow for the maximum regulatory flexibility and compliance.

Conducting Tests

Typically, material characterization and analysis of the device’s components are conducted prior to any biological testing. This involves extracting leachable materials from the device or components at an elevated temperature, and analyzing the leachable extracts for potentially harmful chemicals or cytotoxicity.

Once in vitro testing has been completed, in vivo biological testing can be done based upon the device’s intended use. This testing can range from skin irritation testing to hemocompatibility and implantation testing. Turnaround time for tests can range from three weeks to greater than several months, depending on the specific test data needed. Subchronic or chronic implantation testing can last even longer.

Evaluating the Data

After tests are completed and all data has been collected, it is recommended that an expert assessor interpret the data and test results. This will provide insight on whether additional tests need to be conducted, or whether the existing data provide enough information for an overall biological safety assessment of the device.

Additional Information

If you'd like to learn more about how to plan for biocompatibility testing, and for detailed information on ISO and FDA regulations for medical devices, download the 26-page booklet on Assessing Biocompatibility.

Device Cleaning and Disinfection Validations - A Primer

Background

Scientific advances in both diagnostic and therapeutic medicine have led to the development of new and sophisticated reusable medical devices and instruments for use by health care practitioners and for home/ personal use as well. Manufacturers of reusable medical devices have the responsibility to support product label claims of reusability by providing complete and comprehensive written instructions for the handling, cleaning, disinfection, testing, packaging and aeration for the product between each use. Label instructions for reuse require validation for FDA compliance in order to ensure proper and safe reprocessing of the devices by health care facilities, and validation of the recommended cleaning/disinfection instructions is required prior to labeling the device for reuse.

The FDA places the primary responsibility on the manufacturer for developing and validating methods for effective reprocessing of reusable medical devices. Not only is proving cleaning and disinfection efficacy necessary, but function, physical integrity, and biocompatibility issues may need to be addressed as well. Choosing a validation process for reusable devices should rely on guidance from the FDA and validation methods developed by AAMI, as well as International Standards (ISO, ANSI).

Cleaning Efficacy Tests and Validations

Cleaning is the first critical step in reprocessing reusable medical devices. Cleaning methods are divided into two categories: manual and mechanical/automated. Reuse instructions require validation of the methods in order to assure proper and safe reprocessing of the devices by health care facilities. 

When performing validation tests, the efficacy of the cleaning instructions will be based on the assessment of cleanliness and residuals. Microbial recovery will be utilized for biological residues, total organic carbon (TOC), OPA method, cytotoxicity tests and other methods will be utilized to quantify chemical detergent residues. The purpose of the test is to evaluate the reduction of the residues from soils and chemical reagents used after the cleaning process.

Types of Cleaning Tests and Validations

  1. Manual Cleaning - a documented, validated, and reproducible procedure for effective device cleaning that involves a combination of hands-on-wiping, brushing, and or flushing using validated cleaning solutions, and yields a device that is safe for use or ready for additional processing dictated by the device intended use. This type of method is prescribed when mechanical units are not available or instruments are too fragile or difficult to clean with a mechanical unit. It is often recommended for delicate or complex medical devices (microsurgical devices, lensed instruments, flexible endoscopes, and air powered drills).
  2. Mechanical (automated) Cleaning - a documented, reproducible automated or semi-automated cleaning procedure that is validated for use with medical devices and yields a device that is safe for use or ready for additional processing as defined by its intended use. A method of removing soiling and microorganisms through an automated cleaning and rinsing process, this includes ultrasonic cleaners and washers. Some types of equipment incorporates thermal disinfection processes and/or chemical disinfectant rinses capable of destroying various numbers and types of microorganisms.
  3. Ultrasonic Cleaning Methods - these provide the most effective means of removing soil from some medical devices. These methods are designed for fine cleaning of medical devices, used to remove soiling from joints, crevices, lumens and other areas that are difficult to clean by other methods.
    1. Manual cleaning with sonication- combination of device cleaning by hands and ultrasonic cleaning.
    2. Mechanical (automated) cleaning and disinfection with sonication- combination of automated and ultrasonic cleaning.
  4. Cleaning Verification Test – a test method that verifies the cleanliness of specific devices after manual and/or automated cleaning is completed. These verification tests are part of continuous quality improvement to demonstrate continued compliance with expected cleaning benchmarks. Many options are available to visualize or quantify the amount of residual test soils and cleaning reagent residuals remaining on cleaned devices. One can measure the presence of bacteria, proteins, lipids, carbohydrates, hemoglobin or endotoxin.
    1. In-situ-Method
    2. Indirect sample elution
    3. Viable bioburden assessments
    4. TOC
    5. Protein, Hemoglobin tests

Disinfection Efficacy Tests and Validations

Disinfection is performed by manually soaking a device in a container with a liquid chemical germicide solution (regulated solely by the FDA, solely by the EPA or by both agencies) or it can be accomplished using automated equipment such as washer-disinfectors. The most frequently used chemical disinfectants contain agents like glutaraldehyde, chlorine compounds, quaternary ammonium compounds, phenols, ortho-phthalaldehyde and hydrogen peroxide.

Some factors considered in the selection of a chemical disinfectant for a particular application include device compatibility with the chemical and category of the device to be disinfected (devices are classified into critical device, semi-critical device, noncritical device or environmental surfaces determined by the device’s intended use). How the device will come in contact with the patient, the physical configuration of the device, the type and degree of contamination after use, the physical and chemical stability of the device, and the ease or difficulty in removing the chemical agent after the necessary exposure time should also be considered in the selection of a chemical disinfectant.

Types of Disinfection Tests and Validations

  1. Chemical Disinfection (immersion method/ spray method/ wipe or swab method)
    1. Low-level Chemical Disinfection (environment surfaces, non-critical devices) - a process that kills most vegetative bacteria, some viruses and some fungi, but not mycobacteria and bacterial spores.
    2. Intermediate-level Chemical Disinfection (non-critical, semi-critical devices) - a process that kills viruses, mycobacteria, fungi and vegetative bacteria, but not bacterial spores.
    3. High-level Chemical Disinfection (semi-critical devices, critical devices) - a process that kills all microbial organisms but not necessarily large numbers of bacterial spores.
  2. Thermal Disinfection – application of hot water to decontaminate reusable medical devices. Thermal disinfection selectively destroy microorganisms, and the level of decontamination achieved depends on the exposure time and exposure temperature. Thermal disinfection employs hot water temperatures of 60°C to 95°C (140°F to 203°F)
    1. Short exposure time with high temperature
    2. Long exposure time with low temperature

Outsourcing Your Cleaning and Disinfection Validations

Advancement in diagnostic and therapeutic medicine has led to more sophisticated medical device designs. As these designs become more complex, the process of adequately cleaning and disinfecting and/or sterilizing instruments has become more complex as well. Pacific Biolabs helps manufacturers in the validation of their product claims, and helps ensure patient safety by providing assurance that the product meets FDA requirements. PBL offers a wide range of selections from protocol preparation to validating and performing the routine cleaning and disinfection procedures. PBL will not only validate a given procedure, but will help in designing and creating protocols for a given device.

For a consultation on what is necessary for your device, please visit the Pacific BioLabs website for more information on cleaning and disinfection validation services, and we will also be happy to provide you with a quote on pricing for your specific project.

Resources

The Essentials of Instrument Decontamination (continuing education study guide by Steris)