News for the Combo Product/Device Industries

WuXi AppTec sends out a periodic e-newsletter to our contacts in the combination product/medical device industry. To access previous issues, click here.

If you are not currently receiving the newsletter and would like to be on our mailing list, please email us at info@wuxiapptec.com. Please put "Combo Product-Device News" in the subject line.

For questions about any of these items or other information on WuXi AppTec’s services, contact a WuXi AppTec Account Manager.

December 2014

Contents [click on links for full story]   

 

REGULATORY / INDUSTRY NEWS

WuXi AppTec's Regulatory Affairs team continuously monitors the release of new and revised worldwide regulations and guidances. Staying at the cutting edge of the changing regulatory landscape, we can assist you better by providing assistance in designing testing programs that meet current regulatory philosophies.

To contact a WuXi AppTec Account Manager for more information or to be put in touch with one of our regulatory experts, click here.

U.S. FDA Releases Final Guidance for Infusion Pumps

On December 2, 2014, the Food and Drug Administration announced the availability of the final guidance entitled, ‘‘Infusion Pumps Total Product Life Cycle; Guidance for Industry and FDA Staff.’’   The recommendations in this guidance are intended to improve the safety and effectiveness of these devices and include considerations in preparing premarket submissions for infusion pumps as well as identification of device features that manufacturers should address throughout the total product life cycle. 

From 2005 through 2009, FDA received approximately 56,000 reports of adverse events associated with the use of infusion pumps, including numerous injuries and deaths.1   On April 23, 2010, the FDA issued a draft guidance that included requirements of manufacturers to utilize a Total Product Life Cycle approach in the design and development of devices and (among other things) required manufactures to develop and submit Safety Assurance Cases with 510(k) submissions.  A safety assurance case (or safety case) consists of a structured argument -- supported by a body of valid scientific evidence -- that provides an organized case demonstrating the infusion pump adequately addresses hazards associated with its intended use within its environment of use.

A key element of safety assurance cases involves the inclusion of a hazard analysis with the objective of identifying hazards and potential causes of the hazards.  In its final guidance, the FDA has identified a number of known infusion pump hazards, one of which is biological/chemical contaminations.  In addition, the final guidance identifies biocompatibility issues and concerns that need to be addressed.  WuXi AppTec a global leader in the device industry for the design and performance of both biological/chemical studies and biocompatibility testing programs.  Contact your WuXi AppTec Account Manager for more information about these services or to be put in touch with one of our regulatory experts.

1 FDA Infusion Pump Website: 
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/GeneralHospitalDevicesandSupplies/InfusionPumps/default.htm

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Distinguishing GLP Requirements from ISO 17025 Certification/Accreditation

We occasionally get the question, “What is the difference between a laboratory conducting studies per GLP requirements and a laboratory that meets the requirements for ISO 17025 accreditation?”

Our experts clarify the difference:

Good Laboratory Practices (GLP) is a set of U.S. and EU (OECD) regulations that must be followed when submitting non-clinical laboratory study results to regulatory authorities in support of a product approval application. GLPs, which are limited to and required for the performance of non-clinical safety studies, require quality system and non-clinical study-specific processes. The FDA does not inspect or give certificates of GLP compliance.

ISO 17025 is an international standard related to the quality systems and technical competence of laboratories.  Laboratories achieve accreditations after a thorough inspection process (4 -5 days) where an inspector (s) reviews and evaluates the laboratory Quality System, technical processes/results and staff competence.  The applicability of ISO 17025 is not limited to non-clinical studies and a wide variety of laboratories can achieve ISO 17025 accreditation.  Upon the successful completion of an ISO 17025 accreditation inspection, the facility accreditation scope may include non-clinical safety studies and/or other tests methods.  After the initial inspection, the laboratory is inspected at least once a year to maintain accreditation.

Since 2010, all WuXi AppTec US sites have been ISO 17025:2005 accredited and the scope of our accreditations includes test methods and standards that meet ISO, USP, FDA, EU, MHLW requirements.  We can conduct these tests under GLP and/or Non-GLP regulatory conditions.

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ISO 10993-3 Updated

The International Organization for Standardization (ISO) has recently released the much anticipated update to standard 10993-3: 2014, Biological evaluation of medical devices - Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity. Several major modifications and numerous minor changes were made. Most of the revisions centered on the genotoxicity portion of the document.

An ISO technical committee has been working over the past several years on the guidance document to provide an updated and systematic approach to strategies for selection of hazard identification tests, and risk management, with respect to the possibility of potentially irreversible biological effects arising as a result of exposure to medical devices.  Although the general approach to constructing genotoxicity batteries has not changed in this revision, users of this document are now instructed to justify the sample preparation and testing approaches to ensure that risk is suitably addressed.

Additional features of the revised guidances help provide a consistent and structured approach to the evaluation of data:  a new detailed informational annex describing the performance of exhaustive extracts;  a guide for the interpretation of positive genotoxicity results;  and step-by-step recommendations for all the factors to consider when evaluating a positive result.

After much discussion between international experts, it was also decided to separate the technical components describing how genotoxicity studies can be performed into a standalone technical report.  Expect to see ISO/TR 10993-33 issued soon.

For more information on genotoxicity testing, contact your WuXi AppTec Account Manager.

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TESTING / LAB NOTES

Risky Submissions:  Unknown Compounds in Extractable Leachable Studies Considered Unacceptable by Regulatory Bodies

Over the past year, regulatory agencies have been placing increased emphasis on materials characterization of medical devices. In particular, they are looking to see robust extractable/leachable studies for most devices. Global regulatory agencies are insisting more than ever that device manufacturers identify and understand the toxicological impact of all of the chemicals in their products. The presence of unknowns sets off regulatory red flags.  Interestingly, without an adequate study design, unknowns can be found even in common device materials like nitinol, polymers and hydrophobic coatings.

Unfortunately when unknowns occur, manufacturers are faced with tough choices. They are forced to either repeat testing using much more rigorous approaches to identify the unknowns, or consider the product to have the highest risk categories.  Agencies have indicated that “unknowns” must be considered as carcinogenic and/or genotoxic unless the biological testing has demonstrated otherwise.   This problem doesn’t just occur during development, but it can occur when switching suppliers. Just because a material is considered well established, doesn’t mean that each vendor uses the exact same processing and additives. What might have been considered very routine testing can rapidly become much more troublesome if the right methods and identifications aren’t made.

TIPS FOR SUCCESS

  • Test your product using your processes.
  • Ask your vendor or chemistry department about the number of unknowns they typically see in extractables/leachables studies.  They should be able to identify over 99% of chemicals identified on a routine basis.
  • Complete a toxicological risk assessment of all extracted and leached materials to support your testing and safety claims.

Contact your Account Manager to learn more.

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Largest Medical Material Database

ChemView is WuXi AppTec’s proprietary database touting the largest compendium of medical materials from our years of dedication to the medical device and combo device markets.  This database had been instrumental in allowing industry-leading materials characterization through our extractables/leachables testing program.  Our chemists and toxicologists work to continue to identify and catalog new materials through our testing every day.  Fully characterizing all of the chemicals in your products leads to a stronger submission.

To learn more about our ChemView database and our Materials Characterization Testing, click here.

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Expanding Our Global Footprint:  WuXi AppTec Opens a Representative Office in Israel

This November, WuXi AppTec opened its first office in Israel.  Located in Tel Aviv, the office will promote our broad platform of integrated R&D services to local device, biologics and drug manufacturers.  The new office will also collaborate with Pontifax, a leading heathcare-dedicated venture capital firm also based in Israel, to invest in promising local technologies, particularly those that can potentially advance WuXi’s capabilities.

An office in Tel Aviv will enable our clients to reach out to local representatives who understand the unique pressures of developing new products in Israel.  The office will be headed by Dr. Dana Yarden and is supported by the expertise in our worldwide testing centers.  Dr. Yarden is a distinguished member of the medical device development community in Israel, having lead several successful start-up companies prior to joining the WuXi AppTec team.

"We are excited to establish a presence in Israel and to contribute to one of the most dynamic healthcare innovation ecosystems in the world," said Dr. Ge Li, chairman and CEO of WuXi PharmaTech. "We value the expertise that Pontifax has developed in Israel's biotech industry and look forward to working closely with them to help many of their portfolio companies and other startup companies. This step advances WuXi's mission of helping entrepreneurs in the global life sciences industry to realize their dreams of developing innovative products to benefit the world's patients."

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Environmental Monitoring:  Is Your Program Putting Your Facility At Risk?

The FDA continues to issue 483 observations concerning environmental monitoring programs, many of which are a result of programs that are not robust enough for manufacturers to demonstrate an adequate state of control over their facility.  The guidances are vague when it comes to specific testing programs, but are very clear in the expectation of a well-defined and vigorous program for all controlled environments.

A well-designed environmental monitoring program will take into consideration sampling methods, sampling frequency, sampling locations, data trending and analysis.  The program must also be tailored to a manufacturer’s particular products, process and physical space.

The WuXi AppTec technical team has over 40 years of combined experience in developing successful environmental monitoring programs in the medical device, biologics and pharmaceutical industries.  Let our experts help you establish a robust program that meets your unique challenges.  We offer scalable solutions from consultation to complete turn-key programs including design through execution.  Contact your Account Manager for more information.

Contact your WuXi AppTec Account Manager for more information on our environmental monitoring services and programs.

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UPCOMING EVENTS

WEBINARS

Please join us for a three-part series of FREE webinars:  Biological Evaluations -- Insights for Success

Part 1:   Materials Characterization
Date: December 18, 2014  •  Time: 12:30 p.m. EST
Details/Registration

Part 2:    Biocompatibility Testing
Date: January 22, 2015  •  Time: 12:30 p.m. EST
Details/Registration

Part 3:   Biological Evaluation and Risk Assessment
Date: February 19, 2015  •  Time: 12:30 p.m. EST
Details/Registration
 

SEMINARS

"Breakfast with our Experts"

San Jose area in February/March – Date to be determined

More details available in early January OR contact your WuXi AppTec Account Manager.

 

"Considerations and Challenges Associated with Medical Device Risk Assessment"

SOT (Room 24A)  – March 24, 2015 at 8:30 a.m.

 

TRADESHOWS

MD&M West

February 10-12, 2015  •  Booth # 2831

SOT

March 22-26, 2015  •  Booth # 1833

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