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.

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

June 2014

Contents [click on links for full story]   


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.

Independent Assessment of FDA Device Review Process Management:  Booz Allen Hamilton Report

On June 11, 2014, the Booz Allen Hamilton (BAH) independent assessment of the FDA device review process was released.  As part of its agreement with industry, the Agency committed to meet certain performance goals aimed at increasing the speed and efficiency of its premarket review programs and expediting the clearance of safe and effective medical devices. To that end, the FDA published the Medical Device User Fee Amendments 2013 (MDUFA III) Commitment Letter, which outlines planned measures designed to increase the predictability and efficiency of the device review process.

The final report summarizes the methodologies, findings, and recommendations supporting BAH’s system-based approach in assessing whether FDA has the processes, practices, and resources in place to successfully meet MDUFA III requirements and improve the efficiency and review times for the medical device submission review process. 

To analyze review times between MDUFA III and MDUFA II processes, submissions received during fiscal year 2012 (M2 Received Cohort) were analyzed.  In addition, to assess the impact of specific MDUFA III process improvements, a smaller cohort of submissions (M3 Study Cohort) was also evaluated, which included 37 Premarket Notifications (510(k)s and 28 Premarket Applications (PMAs).

A few key highlights of the report results surrounding the FDA 510(k) device review processes associated with 1) Refuse to Accept (RTA) 2) Substantive Interaction (SI) and 3) MDUFA Interactive Review (IR) are as follows:

RTA Analysis
  • Within the M3 Received Cohort, more than 50% of Traditional 510(k) submissions were rejected within the first RTA cycle.
  • The average number of RTA cycles for Traditional 510(k) submissions within the M3 Received Cohort was 1.6, with submissions from ODE having on average more RTA cycles (1.7) than did submissions from OIR (1.2).
  • Deeper analysis of Traditional 510(k) submissions within the M3 Study Cohort revealed that more than 80% of submissions contained at least one missing or deficient element within the Administrative category of the RTA checklist.  The specific elements within the RTA checklist that were most frequently identified as missing or deficient were the 510(k) summary, identification of prior submissions and inclusion of Standards Data Reports.
Substantive Interaction Analysis
  • A majority of submissions (61%) within the M3 Received Cohort received an Additional Information (AI) Request or Telephone Hold (TH) as an SI, while 20% received a Proceed Interactively (PI) decision and 19% received a Substantially Equivalent (SE) decision
  • On average, submissions from ODE had more SI issues (8.8) than those from OIR (6.2).
  • Among the submissions that received an AI or TH decision in the M3 Study Cohort, 70% (14 of 20) of submissions from ODE had Labeling and Device Description issues, while 100% (7 of 7) of submissions from OIR had deficiencies in Performance Characteristics.
MDUFA Decision Analysis
  • The rates of Not Substantially Equivalent (NSE) and SE decisions remained constant between the M2 and M3 Received Cohorts (83% for SE and 3% for NSEs, respectively).
  • Approximately two-thirds (41 of 61) of all NSE decisions within the M3 Received Cohort were due to lack of performance data.
  • Rates of withdrawn submissions increased 50% from M2 to M3 (4.8% to 7.2%, respectively). Analysis of withdrawn submissions from the M3 Received Cohort revealed that two-thirds were withdrawn during the MDUFA Interactive Review phase.
  • 30% were withdrawn with 10 or fewer days remaining on the review clock. The most frequently cited rationale for withdrawals according to both CDRH review staff and industry representatives was the inability for applicants to provide adequate data to support an SE decision.
  • CDRH review staff frequently cited the inability to resolve deficiencies within MDUFA timeframes as another reason for withdrawn submissions.

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FDA Looking at Endotoxin Stability

Recently the FDA has been asking manufacturers of medical devices and biologics to demonstrate their ability to recover endotoxins following periods of storage and various handling methods.  This is to ensure the presence of endotoxins is not being masked by product materials or packaging.  Does your current testing prove this?

Endotoxin results can be masked by various interactions with materials over time. The FDA is concerned with potentially false low endotoxin results (LER) and the risks such results could create for patients.  So, manufacturers are being asked to conduct stability studies to prove their processes for storing and handling samples do not mask the presence of endotoxin.

While requirements in the current guidance are vague, WuXi AppTec’s team of technical experts has developed proven protocols and guidance to help medical device and biologics manufacturers successfully prove their product safety with regard to endotoxins.  

For more information, refer to the FDA’s June 2012 Guidance for Industry Pyrogen and Endotoxin Testing: Questions and Answers:

Contact your Account Manager today to learn more about our endotoxin testing programs that can help you prove the safety of your new and existing products.

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Infusion Pumps:  Impact of the Recent Recall Activity Level

This year has seen a flurry of infusion pump recalls from a variety of manufacturers.  While much of the recent activity has been a result of software issues, some of the problems have been related to materials and mechanical failures.  For many manufacturers, these issues should spur the question: “Is our product at risk?”

Quality teams reviewing their safety testing must consider whether the testing is comprehensive enough in the current environment.  Products generating reportable events such as recalls draw the scrutiny of regulatory agencies.  When regulators come on-site for routine visits, this often translates into detailed reviews of master device files and all of the testing and validation work done on the product. 

At WuXi AppTec, we have already seen an increase in requests from manufacturers for testing programs that cover a wide range of studies – from extractable chemicals and drug interactions to cleaning effectiveness, biocompatibility and toxicity.  To satisfy the regulatory requirements, your remediation programs should provide a comprehensive evaluation of risk from the materials and an estimation of risk that can arise during clinical-use situations.

Our team of toxicologists, regulatory professionals and re-usable device technical experts can help design a testing program that links your materials characterization and biocompatibility testing with a biological evaluation to prove the safety of your unique infusion pump. 

Click here to learn more about our proven testing programs for infusion pumps or contact your Account Manager for more details.

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ISO Radiation Sterilization Standard Adopted

With the adoption of ISO/TS 13004:2013 by ANSI/AAMI, medical device manufacturers have additional clarity when it comes establishing a sterile dose for radiation sterilization.  The standard extends methods for selection and substantiation of sterile doses (17.5, 20, 22.5, 27.5, 30, 32.5 and 35kGy) based on specified upper limits of average bioburden, giving manufacturers more recognized options to meet their specific testing needs.  Previously the ISO requirements included only two methods:  Method VDmax 25 (for establishing a sterilization dose for a product with average bioburden less than or equal to 1000) and Method VDmax15 (for establishing a sterilization dose for product with an average bioburden less than or equal to 1.5.)  

To learn more about how this standard may affect your testing plans, contact your Account Manager, who can also put you in touch with our team of technical experts.  For information on WuXi AppTec’s Sterilization Management Program, click here.

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WuXi AppTec Expert, Gordon Ely, Confirmed as Co-Chair of AAMI Aseptic Processing TAG

Gordon Ely, a WuXi AppTec Senior Technical Specialist, was recently confirmed as the co-chair for AAMI ST/WG09, Aseptic Processing, which is the U.S. Technical Advisory Group (TAG) for ISO/TC198/WG09. He joins the already large number of WuXi AppTec experts with leadership and committee member roles in international governing bodies.  WG09 focuses on a series of standards related to aseptic processing, including: general aseptic procedures, filtration, lyophilization, clean-in-place, steam-in-place, isolators, and aseptic processing of medical devices, combination products, and cell-based health care products.

Located in our Atlanta facility, Mr. Ely works with the team providing our clients with sterilization management services.

To learn more about WuXi AppTec’s sterilization management services, click here.

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New!  Industry-Leading Turnaround Time for Mouse Micronucleus Assay

We heard your request for faster turnaround times for the GLP Mouse Micronucleus Assay and we delivered! 

WuXi AppTec is now able to provide you with a 48-day GLP assay, down 7 days from the previous 55-day turnaround time.  This significant advancement is a reflection of our continuous commitment to helping you speed the process of your medical device testing.

To learn more about all of our biocompatibility testing services, click here.

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Recertification Programs Require More Than Biocompatibility Testing

As the regulatory environment has shifted in recent years to the expectation that manufacturers prove safety of their products through biological evaluations, many commercialized products test files are falling short.  It used to be that a manufacturer needed only to keep biocompatibility testing up to current standards.  However, now regulatory agencies are looking for safety data that includes materials characterization and risk assessment in addition to biocompatibility testing.  

The problem for manufacturers is that these additional evaluations may not have been done as part of the original submissions package because there were fewer requirements for this type of work. Furthermore, regulators are also reviewing original sterilization and cleaning/sanitization process validations to make sure those also meet current expectations, even if there are no specific indicators of process failures.  In today’s tough regulatory environment, deficient files are causing 483s and warning letters.  Addressing these letters takes time and resources away from other important development activities.

Making sure you have the needed safety data without over testing is crucial for successful management of your products.  WuXi AppTec’s team of technical and regulatory experts has helped many medical device manufacturers ensure their product submissions comply with current regulations.  Furthermore, we can assist in identifying the most efficient approach for recertification – minimizing the total testing but ensuring all product lines are covered.

Contact your Account Manager today to learn about our Legacy Testing Programs and how they can work for you.

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Grand Opening to be Held for New Materials Characterization Facility

Please join us as we celebrate the grand opening in August of or new materials characterization facility. Located in St. Paul, near our existing site, this new facility was designed specifically to serve our customers’ growing need for quantifying the chemical safety of materials used in their products.

The 20,000-square-foot laboratory will offer expanded capacity for existing services, like particle identification and extractable/leachable testing, and add a new service—dynamic light scattering for nanoparticle characterization. Designed on a unique flexible floor plan, the facility will allow rapid scale-up of technologies to increase capacities for chemical analysis of medical materials.


Date:     Tuesday, August 12, 2014

Time:     6:30 a.m. to 9:30 a.m. – Breakfast Open House

                7:30 a.m. – Ribbon Cutting

For more information on WuXi AppTec's materials characterization capabilities, click here.

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