News for the Combo Product/Device Industries

WuXi AppTec sends out an e-newsletter approximately every quarter to our contacts in the 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.

December 2009

Contents [click on links for full story]


News from WuXi AppTec

Revision of AAMI ST 67 Addresses Sterility Assurance Levels (SALs)
A revision is in process for the AAMI ST 67: 2003 document that addresses sterility assurance levels (SALs), titled Sterilization of medical devices - Requirements for products labeled "Sterile". The current ST 67 document allows an SAL of 10-3, 10-4 or 10-5, in cases where a product could not withstand a 10-6 sterilization process. However, this allowance is contingent on several factors, such as the inability to redesign the product such that it could be sterilized to a 10-6 SAL, and the product having unique benefits with no alternative product being available. The revision of ST 67 will allow use of SALs other than 10-6 without the former restrictions, by encompassing risk assessment requirements and guidance. This will enable manufacturers of sterilization-sensitive products, such as combination products containing biologics or pharmaceuticals, to investigate the use of terminal sterilization versus aseptic manufacturing. For example, much lower doses of radiation sterilization (e-beam or gamma) can be used to sterilize a product to a 10-3, 10-4 or 10-5 SAL that otherwise might have been detrimentally affected by higher doses needed for a 10-6 SAL. Since there are several AAMI/ISO methods available for validating low doses of radiation, terminal sterilization is now a viable option for many products. The AAMI ST 67 revision is expected to be available in 2010.

WuXi AppTec, long an industry leader in sterilization validation testing, already has the protocols in place for the performance of these low-dose radiation validations. We encourage clients to contact the experts at our Atlanta facility for further information.

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In Vivo Assays is Subject of WuXi AppTec Presentation at ASM Biofilm Conference
Dr. Linda Hansen, Director of Custom Studies in the In-Life Program at WuXi AppTec’s St. Paul facility, recently presented at the American Society for Microbiology’s 5th Biofilm conference in Cancun, Mexico. Her poster, entitled, “Development of Validated In Vivo Assays to Determine the Efficacy of Antimicrobial Products to Reduce Device-Related Biofilms“,co-authored by Mary Mochinski, Dave Johnson, and Don Palme, was part of the “Industrial and Applied Biofilm Research” topic area. The conference was attended by approximately 450 scientists from around the world, and included presentation topics such as, “Biofilm Development”, “Biofilms in Medical and Dental Infections”, and “Biofilm Resistance Mechanisms and Control Strategies”. Dr. Hansen also attended a one-day workshop on Animal Models for Studying Biofilms. WuXi AppTec, Inc., is committed to providing the most current and relevant testing services, and sending senior scientific staff to such meetings is one of the many ways we assure that we remain current on cutting-edge methods and research findings in areas such as microbial biofilms. WuXi is a leader in providing custom Anti-microbial Efficacy testing, both in-vivo and in vitro, for evaluation of anti-microbial components of medical devices aimed at reducing implant infections and biofilm formation.

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Innovations / Lab Notes

Systemic Toxicity Testing of Gel Medical Devices Requires Special Considerations
Among the biological effect categories for testing consideration identified in ISO 10993 Part 1: Evaluation and Testing are acute, subacute, subchronic, and chronic systemic toxicity. Conducting this testing using polar and non-polar extracts has been the historical standard. However, testing gels using extracts may have problems associated with solubility and physiological compatibility.

If the gel is soluble in one or both polar and non-polar extract media, then adjustments must be made for the dosage level of the extract solution. If non-soluble, standard extraction and dosage may be used as indicated in ISO 10993-12: Sample Preparation and reference materials. Use of extracts for acute systemic toxicity testing is the standard and can be successfully employed for subacute/subchronic testing with careful consideration of solubility implications. Also, for implantable devices, combining the evaluation of local effects after implantation (ISO 10993 Part 6: Tests for local effects after implantation) and the evaluation of systemic toxicity (ISO 10993 Part 11: Tests for Systemic Toxicity) into a single study has become an approach that is acceptable to the regulatory agencies for subacute, subchronic, and chronic testing.

Clients that utilize the expertise of WuXi AppTec staff for designing and conducting systemic toxicity studies of gels (acute, subacute, subchronic, and chronic) are realizing subsequent efficiency and financial benefits.

The testing of gel-based materials or materials that can go into solution are problematic and consultation with an expert maybe helpful to prevent regulatory issues.

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Training Seminar in Copenhagen Addresses ISO Requirements
WuXi AppTec participated in leading a week-long training seminar designed to bring European medical device companies up to date with all of the requirements of ISO 10993 testing. Held in Copenhagen, Denmark the week of November 9th through the 13th, the training was attended by employees of companies ranging from large global medical device companies to smaller start-ups.

Dr. John Lang (co-author of several of the ISO 10993 documents), Dr Raju Kammula (former Chief Toxicologist, US FDA) and Dr. Don Palme II (V.P. Toxicology and ILS, WuXi AppTec) offered in-depth discussion of the current requirements and the future directions of the safety testing required for submission of medical devices in Europe, US and Asia. In particular, discussions focused not only on the different requirements between the regulatory agencies but also on future directions and upcoming changes. Interactive modules had the participants working in teams to analyze sample projects and workshops included one that exposed attendees to the same training that regulatory reviewers undergo.

The entire training session was sponsored by Synergus, the European distributor of WuXi AppTec’s biocompatibility testing. Synergus, which is based in Stockholm, is greatly active in promoting training to the ISO standards in Europe and this was the second program they have offered in the last three months. For information on future training sessions, please contact WuXi AppTec or Synergus.

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ISO/TC 194 / WG6 and WG9 Meetings Focus on Revisions to ISO 10993 Parts 3 and 4
Dr. Randy D. White, Ph.D., Senior Director, Toxicology, at WuXi AppTec and a member of the United States Technical Advisory Group for Biological Evaluation of Medical Devices attended the recent meeting for ISO/TC 194 Working Group 6 (Mutagenicity, Carcinogenicity, and Reproductive Toxicity) and Working Group 9 (Effects on Blood). The primary focus of the WG 6 meeting was to discuss the comments received on the revision of ISO 10993 Part 3: Tests for Genotoxicity, Carcinogenicity and Reproductive Toxicity. The primary focus of the WG 9 meeting was a general discussion on what parts of ISO 10993 Part 4: Selection of Tests for Interaction with Blood need to be changed.

Great strides were made in addressing the Part 3 comments with hopes of resolving all comments at the next meeting of WG6 June 28, 2010, in Berlin with the goal of harmonization of testing. It may not be well known, but the FDA does not accept the Part 3 document as it is currently written. The FDA (as well as Japan) supports an approach for sample preparation based on percentage of extractables in the test sample. A representative of the FDA at the meeting indicated that a battery of three genotoxicity tests is currently acceptable to the FDA, such as the Ames test, the Mouse Lymphoma Assay, and the in vivo Mammalian Micronucleus Test. However, the FDA representative indicated that the in vivo test might not be required if sufficient written justification against doing that test is provided.

A common theme in the WG 9 discussions was a desire to provide specific test protocols for evaluation of effects on blood. To facilitate this, in part, it was decided that round-robin testing to validate a protocol for the hemolysis test would be performed by several laboratories. One of those laboratories will be WuXi AppTec in St. Paul, MN. Discussion on specific protocols for other tests, as well as the results of the hemolysis test validation, will be continued at the next meeting in Berlin the week of June 28, 2010. Also of interest was a comment by a representative from the FDA indicating that the FDA currently wants to see the following tests for evaluation of effects on blood: Hemolysis (direct and indirect), Compliment Activation (C3a and SC5b9 [both assays]), and in vivo Thrombogenicity (without anticoagulant).

As a result of attendance at these and other relevant meetings, WuXi AppTec has established the assays that are currently accepted for compliance with ISO 10993 Part 3 and Part 4 testing. By continuing to stay well informed of the current trends in geographic differences, WuXi AppTec can help its clients realize efficiency and financial benefits.

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UPCOMING MEETINGS

Please stop by and see us at these upcoming shows:
MD&M West – February 9-11 at the Anaheim Convention Center – Booth # 2935
Interphex – March 4-5 at the Puerto Rico Convention Center – Booth # 217
BIOMEDevice – April 21-22 at the Boston Exhibition & Convention Center– Booth # 1015

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