Evaluation of Immunogenicity and Allergic Reactions to Medical Device Materials and Combination Products

Collagen - an example of a biological material used as part of medical devices.

Collagen - an example of a biological material used as part of medical devices.

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 ofcomplement 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.

Pacific BioLabs performs immunogenicity testing, has an experienced staff, and is here to help in determining what may be needed for your device. 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.

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 Announces New QA Department Manager

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.

Pacific BioLabs Appoints Michael Yakes, PhD as VP of Toxicology

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.

FDA Publsihes New Draft Guidance on Combination Products

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

Venture Capital Funding for Life Sciences: Q & A

At a basic level, Venture Capital (VC) funding can be described as financing provided to startups or other relatively early-stage business that are perceived to have significant growth potential. VC funding is a key to ensuring continued innovation, as companies with new ideas or technologies typically need a large amount of initial capital before profit can be realized. Most VC firms operate on a high risk / high reward model: it is expected that most companies that are funded will fail and lose money, while a small number of ventures will succeed and deliver a very high return on investment.

How does Venture Capital funding affect the Life Science Industry and why is it important?

Venture Capital funding ultimately plays a significant role in influencing the rate of new scientific advancements and products. In a typical year, the Life Sciences Industry receives billions of dollars of venture capital funding. Large drops in life science VC funding (such as the one experienced during and after the 2008-2009 recession) will negatively impact the industry’s job market as well as overall production of new innovations. Other factors can affect life science funding levels, including changes in the regulatory landscape, changes in perceived industry risk levels, and competition for VC capital from other sectors or industries.

Competition for VC capital in particular has affected life science funding in the last decade. Life science ventures often require high funding levels, and the average time to a return on an investment can be long – especially compared to the tech sector. This has led to capital moving away from traditionally strong areas such as pharma and biotech towards software and tech firms. Over time, this shift in funding will be detrimental to the Life Sciences Industry; without a continued influx of capital, the development of new life saving drugs and medical devices will inevitably decline.

What did the Venture Capital landscape look like for Life Sciences in 2014?

Startups and businesses in the Life Sciences sector have been patiently waiting to see a stable increase in VC funding since the decline in 2009. While there has been a gradual increase over the years, investors have still shown some hesitation in returning to pre-2009 levels. However, 2014 (up through Q3) proved to be a very promising year.

2014 had the strongest start for VC funding for Life Sciences since 2008. Quarter two of 2014 also had the highest quarterly total since the first quarter of 2001, and showed a 26% year over year and 35% quarter over quarter increase for average deal size, according to PricewaterhouseCoopers LLP.

With the massive increase in funding in the second quarter of 2014, it wasn’t shocking when the third quarter experienced a 35% quarter over quarter decrease in funding. The third quarter also showed a decline in total deal volume, but showed an increase in funding when compared to its counterpart in 2013. This is due to a 12% year over year increase in deal size. This has been the trend for every quarter in 2014 so far (see graph below).

When the final Life Science VC investment totals for 2014 are gathered, it’s likely that this will be one of the strongest years ever for funding, especially in biotechnology.

Why was 2014 one of the strongest years for VC funding of Life Sciences?

With the recent activity of venture-backed companies going public and the continued strength of the Initial Public Offering (IPO) market, it’s likely that investors affiliated with companies that have gone public will start a new cycle of investments.  Startups and smaller businesses will have a chance to lobby for new potential investors.

New classes of investors have also begun entering the market, providing VC funding. According to Greg Vlahos, Life Sciences partner at PricewaterhouseCoopers LLP, there is an “emergence of new investors in the innovation economy, including the rise of hedge funds, mutual funds, and other non-traditional investors making direct investments into presumably pre-IPO companies.”

Given the funding trends in 2014, and the emergence of new investors and new classes of investors, we are optimistic that the future of Venture Capital funding for Life Sciences is bright.


  1. “MoneyTree™ Life Sciences Report, Biotech trending high.” November 2014. Web. 18 Dec. 2014.

  2. “MoneyTree™ Life Sciences Report, Biotech soars to record high.” August 2014. Web. 18 Dec. 2014.

  3. “MoneyTree™ Life Sciences Report, Biotech deals rising.” May 2014. Web. 18 Dec. 2014.

  4. National Venture Capital Association. “VC Industry Overview.” Web. 18 Dec. 2014.

  5. “Life sciences venture capital investments soar in Q2 to highest level since 2007, according to the MoneyTree Report.” 25 Aug. 2014. Web. 18 Dec. 2014.