Pacific BioLabs and Nutek (a contract sterilizer specializing in e-beam irradiation) work closely together to perform the microbiology and sterilization needed for medical device sterilization validation programs. In this presentation we share some of our knowledge and advice on how to ensure a successful validation, which is a key factor in a medical device development program.
As devices become more complex, biocompatibility and material evaluations must necessarily become more complex and thorough as well. Allergic and immunogenic reactions are a serious safety concern not only for pharmaceuticals, but because of increasing device complexity, they are also an emerging concern for devices. In the past, evaluation of devices looked only at allergic potential (not at immunogenicity), and was done by looking for sensitization to the device itself. This testing - for a delayed-type of hypersensitivity in guinea pigs - is still required for all devices.
Complex and Novel Materials Require More In-Depth Testing
However, it has become more common to see devices comprised of engineered biomaterials (such as stents coated in collagen or using other biologically-derived scaffolds.) Drug/device combination products pose novel immunogenicity safety concerns – for example, nano-particles often combine natural or synthetic polymers with drugs. Nano medicines such as liposomes, carbon nanotubes, dendrimers, and polymer conjugated proteins have physical, chemical, and biological properties that may attract the attention of the immune system.
These complex devices, and those containing novel materials (e.g., plastics, polymers, metals, ceramics, biological materials) or devices that are lacking adequate testing for immunotoxicity, should also be tested for additional immune responses.
It becomes important to evaluate immunogenicity because the results of an immunological response can be so serious. Immunological effects include inflammatory responses, immunosuppression, immunostimulation, or autoimmune responses.
Performing Immunogenicity Testing of Devices
Testing for immunogenicity may involve animal implantation studies followed by analysis of serum for changes in total circulating IgG, and/or antigen specific responses by ELISA. Hemocompatibility testing should include measurement of complement activation. This can be performed in vivo or in vitro. Device material or extracts are incubated with specially handled human serum and then activated complement cascade proteins are measured by ELISA. Alternatively, serum from animals implanted with the device can be tested for complement activation. These bioanalytical tests provide information to manufacturers and regulators about the safety and biocompatibility of the product.
It is important to identify early whether your device may need an immunogenicity evaluation, and to begin collecting this data along with your biocompatibility data to support your 510(k) or PMA submission. Pacific BioLabs has an experienced staff and is here to help in determining what may be needed for your device.
Additional information can also be found at the FDA website, including a flow chart to determine whether immunotoxicity testing is necessary: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080495.htm
PBL is pleased to announce that Haihong Bao has joined as the new Quality Assurance Manager.
Haihong brings more than 10 years of experience working in CRO environments, including 5 years QA management experience focusing on toxicology, analytical chemistry, and bioanalytical studies and reports.
Her previous CRO experience includes 5 years at JOINN Laboratory, a CRO in Beijing, China, 2 years at MicroConstants, and 4 years at ITR Laboratories as a Toxicologist.
April 9, 2015
HERCULES, California –Pacific BioLabs, a GLP/GMP pharmaceutical and medical device contract research organization, today announced the appointment of Michael Yakes, PhD as Vice President of Toxicology, responsible for all toxicology, PK/ADME, bioassay, and biocompatibility testing.
Dr. Yakes has spent 14 years in the pharmaceutical industry, directing pharmacology programs and managing multidisciplinary teams at Exelixis, and was recently the Senior Director of Translational Biology for Cleave Biosciences, overseeing toxicology, DMPK, and pharmacology studies.
“We are extremely pleased to welcome Mike to PBL,” said Tom Spalding, President of Pacific BioLabs. “Mike has an outstanding track record in the pharmaceutical industry, and brings fantastic energy and leadership skills to the position. I’m confident that our current clients will enjoy working with Mike, and that his entrepreneurial skills and business acumen will help PBL continue to grow.”
About Pacific BioLabs
Pacific BioLabs is a contract research organization providing a broad array of development and manufacturing support services to the pharmaceutical, biotech, and medical device industries. By supporting these industries through GLP and GMP testing services, Pacific BioLabs helps to bring life-saving and life-improving therapies and devices to patients who need them. Located in Hercules, CA, Pacific BioLabs operates out of a state-of-the-art, purpose-built 32,000 square foot facility overlooking the San Francisco Bay. For more information, please visit www.pacificbiolabs.com.
For anyone in the medical device or pharmaceutical fields, it's important to stay up to date on current Good Good Manufacturing practices.
In January, the US FDA published a draft guidance updating the cGMP requirements for combination products. The guidance defines what a combination products is, and contains application requirements for specific types of combination products: prefilled syringes, drug-coated mesh, and drug eluting stents.
The guidance can be found on the FDA website: cGMP Guidance for Combination Products