Accelerated Aging Package Testing

By: Pal Khangaldy & Wendy Mach

The Packaging Department at Nelson Laboratories is often asked by manufacturers “What do I need to do to validate my packaging?” or “What package testing do I need to have performed in order to comply with regulations?” There is not a one-size-fits-all answer to these questions as unique product, packaging, and sterilization combinations require unique testing combinations. However, there are some basic testing concepts that apply to all product and package types: expiry testing; strength, integrity, and microbial barrier testing; and package distribution testing.

FDA and Accelerated Aging

ChamberFDA requires testing to demonstrate that the packaged product will maintain its integrity and sterility when stored over time, and this testing is required to establish an expiry date. Tests that meet these regulatory requirements are accelerated aging testing, real-time aging testing, or a combination of both. It is important to note that accelerated aging testing does not replace real-time aging testing. In a perfect world with unlimited time and resources, manufacturers would only conduct real time aging tests. However, this type of testing is not practical for manufacturers that need to quickly get their product on the market – they do not have the time to put a package system on the shelf for two or more years and await the results. Because of this, accelerated aging was developed as it meets the testing requirements by FDA.

Accelerated Aging Testing

The concept behind accelerated aging testing: Increasing the temperature escalates the chemical reaction rate of the samples and results in deterioration of materials which simulates artificial aging. Every 10°C increase in temperature doubles the reaction rate. This concept is based on the Arrhenius equation and is explained in further detail in ASTM F1980 Standard Guide for Accelerated Aging of Sterile Barrier System for Medical Devices.

There are limits to this equation, as increasing the temperature too high can prematurely destroy the product/package system. Test temperatures should not exceed 60°C. The temperature used most often in the industry for accelerated aging is 55°C and is the temperature Nelson Labs recommends.

Next Steps

Strength, integrity, and microbial testing verify that the packaging is intact after aging tests. These types of testing are the topics of our next blog post. For more information on real-time or accelerated aging testing, contact your Nelson Labs Account Manager or our Service Center via ServiceCenter@NelsonLabs.com or 801-826-2088.

 

 

 

Nelson Labs’ Scientists Awarded Best Published Paper 2017

By: Daniel Olsen, M.S. SM(NRCM)

Nelson Laboratories scientists, Michelle Lee, Audrey Turley, and Daniel Olsen, in collaboration with scientists from the Japanese National Institutes of Health, recently published important research for the development of in vitro skin irritation testing for medical devices. Their article, “Proof of concept testing of a positive reference material for in vivo and in vitro skin irritation testing”, was published in the Journal of Biomedical Materials Research.

The article reports the discovery, development, and testing of the first available material to be used as an extractable positive control for in vitro irritation testing. The material is the first shown to elicit a positive irritation response in both polar and non-polar extraction solvents. This discovery of an extractable positive control material was a key step in the progress of in vitro skin irritation testing for medical devices and helped prepare the way for the recently completed international validation of the irritation test method.

The article was awarded the Best Published Paper honor for 2017 from the Medical Device and Combination Products Specialty Section (MDCPSS) of the Society of Toxicology (SOT). MDCPSS is composed of many experts within the medical device industry including a dynamic mix of scientists from device manufacturing companies, contract research organizations, regulatory agencies, and consulting companies. The award will be presented in March at the 2018 SOT Annual Meeting in San Antonio, TX.

Martell Winters is Convener for ISO WG16

martell_winters_3It was recently announced that Martell Winters, B.S., RM/SM(NRCM) was appointed and approved as convenor for a three-year term of a new ISO working group, WG16, on vaporized hydrogen peroxide sterilization. The new working group is tasked with developing a new standard to provide requirements and guidance for developing sterilization processes for vaporized hydrogen peroxide. The ISO document has been named ISO 22441, Sterilization of healthcare products – Low temperature vaporized hydrogen peroxide – Requirements for the development, validation and routine control of a sterilization process for medical devices.

“I’m honored to be considered and appointed as convenor of WG16,” Martell said about the appointment. “I look forward to working with the members of the group as we develop this new standard. There are a good number of experts in vaporized hydrogen peroxide involved, so I am confident that our efforts will result in a technically correct and useful standard.”

Previously, vaporized hydrogen peroxide sterilization was addressed under the general sterilization criterial standard, ISO 14937, which provides general requirements for any sterilizing agent which does not already have a specific standard. It was felt by the international community that vaporized hydrogen peroxide had gained enough acceptance and use in the industry that it merited having its own standard.

The US body which will be participating in this ISO working group will be AAMI WG16, which is also a new working group and is currently being established. Anyone who has interest in being involved with this new AAMI working group should contact AAMI.

Cytotoxicity Failure Program

Cytotoxicity Failures

Cytotoxicity testing is designed to demonstrate if there are cytotoxic leachable substances from medical devices or materials. Cytotoxicity testing is the most sensitive biocompatibility test and is used for safety testing of all medical devices with patient contact.  It is also used frequently as a routine screening test for raw materials.

Occasionally, a device or material will exhibit a level of cytotoxic reactivity that is higher than what is allowed by the ANSI/AAMI/ISO 10993-5 standard and will result in a failed test. Although your product may have failed a cytotoxicity test, it doesn’t necessarily mean that your device or material is unsafe for clinical use. It simply means that you are obligated to identify the source of the failure and assess any toxicological risks. There are several possible causes for a failure, and Nelson Labs provides services to help you assess the failure and any toxicological risks.

Cytotoxicity Failure Program

Reconstructed human epidermis (RHE) for in vitro skin irritation and sensitization testing.

In the past, if your product failed cytotoxicity testing, you would need to send new samples for additional testing to determine the cause of the failure. We have recently added a new service to help our customers potentially save time and money when conducting these evaluations. If you request the Nelson Labs Cytotoxicity Failure Program when submitting your samples to the lab, we will store a sample of the extraction fluid from your cytotoxicity test until you receive your test results. In the case of a failing result, we will connect you with one of our subject matter experts who will help you develop a plan for investigation. Because we have retained a sample extract from your original cytotoxicity test, we can quickly test the retained fluid without the need for a new sample. We typically test for metals in these cases, as the presence of metals from the manufacturing process, handling, or colorants is a primary cause for failed cytotoxicity tests.

If the test detects cytotoxic metals in the extract, we will then contact you with details regarding initiating a toxicological risk assessment. Our toxicologists can assess the metals and determine if the concentration would be sufficient to lead to any patient safety issues. This analysis can also be helpful to decide if an investigation regarding the source of the contamination should be conducted.

The cytotoxicity test is a highly sensitive toxicity assay which is designed to determine if there are cytotoxic leachable substances or surface contaminants present in medical devices or raw materials. It is required testing for most medical devices and is used frequently as a routine screening test for raw materials and cleaning validations.

There are several possible causes for a failure, and Nelson Labs provides services to help you assess the failure and any toxicological risks.

If you would like to discuss this program, contact your Account Manager or sales@nelsonlabs.com.

Sterigenics International LLC Acquires Toxikon’s European Laboratory Business

Acquisition creates the leading global extractables and leachables lab testing platform to serve the pharmaceutical and medical device industries

CLEVELAND, OH. – Oct. 31, 2017—Sterigenics International LLC announced today that it has acquired Toxikon Europe N.V., the European division of Toxikon Corporation, a Bedford, Mass.-based preclinical contract research organization. Terms of the deal were not disclosed.

Toxikon Europe N.V. provides a suite of integrated analytical, material characterization and microbiological services to the pharmaceutical, medical device and biologics industries. The company’s unrivaled extractables and leachables (E&L) testing expertise and leading database enhance the flexibility and speed with which its life science customers can bring their products to market.

This acquisition provides a more comprehensive service offering and a platform for growth for Sterigenics International’s Nelson Labs business. Nelson Labs will now offer Toxikon Europe’s leading E&L capabilities to its customers around the world and in kind, offer Nelson Labs leading microbiological services to Toxikon Europe’s customers.

“Toxikon Europe’s geographic foothold and expert analytical testing platform enable our global expansion and ability to provide significantly greater value to customers,” said Michael B. Petras Jr., CEO of Sterigenics International. “We are excited to welcome a strong management team, with over 150 years of aggregate industry experience, and the highly trained Toxikon Europe employees to our company.”

Toxikon Europe’s capabilities are both complementary and additive to Nelson Labs’ existing testing portfolio and, in combination, make Nelson Labs one of the premiere global E&L laboratory testing platforms for the pharmaceutical and medical device industries.

As part of this deal, Nelson Labs and Toxikon USA will enter into a long-term supply arrangement under which Nelson Labs will outsource in-vivo biocompatibility to Toxikon USA.

“The acquisition of Toxikon Europe and our ongoing partnership with Toxikon USA support our strategy to offer greater breadth of services to meet the demands of our rapidly growing, global customer base,” said Jeff Nelson, President of Nelson Labs. “We are now able to serve the pharmaceutical and medical device industries continuously from the early stages of product development through manufacturing, sterilization, and quality assurance testing.”

“For Toxikon Europe, the acquisition by Sterigenics International validates our success and provides our customers with additional resources,” said Dr. Laxman Desai, President and CEO, Toxikon Corporation. “Our team at Toxikon USA looks forward to our continued partnership with Nelson Labs.”

Jos Bollen, Managing Director, Toxikon Europe, added, “Our customers, who are increasingly focused on quality and safety, will continue to receive the superior service and quality they have come to know from Toxikon Europe. In addition, our breadth of service and our reach will be enhanced with the expertise and industry leadership of Sterigenics International’s Nelson Labs.”

About Sterigenics International LLC
Sterigenics International LLC, along with its affiliates, is the world’s leading, fully integrated protector of global health.  With over 500 years of combined scientific expertise, the company ensures the safety of healthcare by providing mission-critical services to the medical device, pharmaceutical, tissue and food industries.  Sterigenics International operates 60 facilities in 13 countries across the Americas, Europe and Asia.  The company has 2,600 employees globally and touches the lives of more than 180 million people around the world each year.  With more than 6,000 customers worldwide, Sterigenics International goes to market through its three best-in-class companies – Nelson Labs, Nordion and Sterigenics – with the mission of ensuring the safety of healthcare each and every day.  Nelson Labs offers leading microbiological and analytical testing and consultancy to customers in the medical device, tissue/implantable, pharmaceutical and biologics fields.  Nordion is the world’s largest provider of Cobalt-60 used in the gamma sterilization process as well as medical isotopes used in the diagnosis and treatment of various diseases and cancers.  Sterigenics provides contract sterilization and ionization services for the medical device, pharmaceutical, food safety, and high-performance materials industries.  Sterigenics International LLC is owned by private equity firms Warburg Pincus and GTCR. Learn more about Sterigenics at sterigenics.com, about Nordion at nordion.com and about Nelson Labs at nelsonlabs.com.

About Toxikon Europe N.V.
Toxikon Europe is an independent, privately owned Contract Research Organization, specialized in providing premium Extractable & Leachable Services to the Pharmaceutical Industry. Based in Belgium, Toxikon Europe supports Pharma Companies – across the Globe – in developing worldwide compliant
(FDA, EMA) Testing Strategies to qualify Container/Closure Applications and Pharmaceutical Production Equipment from an Extractable & Leachable Perspective. In addition, the Toxikon group also provides Biocompatibility Testing Services (In-Vivo and In-Vitro testing) to both the Medical Device and the pharmaceutical Industries. Toxikon is ISO 17025 Accredited, GLP-Certified and GMP Accredited. Toxikon is also FDA registered.

Media Contacts:
Sterigenics International – Amy McGahan, 216-241-3027, amcgahan@dix-eaton.com
Toxikon Europe N.V. – Jos Bollen, 32 16 400484, Jos.Bollen@toxikon.be
Toxikon USA – Branden Morris, 781-275-3330 X 7141, branden.morris@toxikon.com

AAMI Sterilization Standards Meetings Update

By: Emily Mitzel, MS

The AAMI Sterilization Standards Meetings were held on 16-18 October 2017.  There were almost 300 medical device manufacturers, FDA personnel, heath care facility personnel, testing laboratory personnel, consultants, and others in attendance.

One item of interest from USFDA/CDRH is that the Office of Device Evaluation (ODE), Office of Compliance (OC), and Office of Surveillance and Biometrics (OSB) are merging into a single structure specified as the Center for Devices and Radiological Health (CDRH) Total Product Life Cycle (TPLC).

A second item of interest is the Accreditation Scheme for Conformity Assessment (ASCA) in which FDA is ensuring testing laboratories are consistent and are complying with current standards. https://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/ucm558632.htm

Medical Device Reprocessing Update:

  • AAMI TIR30:2011 Compendium of processes, materials, test methods, and acceptance criteria for cleaning reusable medical devices is in the process of review and is being rewritten.
  • ISO/FDIS 17664 – Sterilization of Medical Devices Information to be provided by the device manufacturer for the processing of reusable medical devices last published in 2004 will be publishing a new version (hopefully by the end of 2017).
  • A new document currently titled ISO/NP 22913, Processing of health care products — Information to be provided by the medical device manufacturer for the processing of medical devices — Part 2: Medical devices not intended for direct patient contact, was approved and will be written.
  • The current draft of ISO 15883-5 – Test soils and methods for demonstrating cleaning efficacy is undergoing a major revision.

The dates of the next AAMI Sterilization Standards meetings are:
19-22 March, 2018
22-25 October, 2018