We are now on the threshold of a revolution in the evolution of a wide range of advanced drug-device combination products. In 2004 the market for these products was estimated to be $5.9 billion, and is forecasted to grow to $11.5 billion by the year 2010. It is vital therefore, at this time to examine in detail existing sterilization technology options for this class of products.
Radiation Sterilization of Combination of Drug-Device Products
The most widely used technology for the sterilization of single use medical products namely that of gamma radiation, which over the last fifty years has become the preferred method for the terminal sterilization of approximately 45% of all the world's single-use medical disposables. This in more than 170 commercial gamma irradiators worldwide... of which 56 are located in the USA sterilizing annually in excess of 260 million cubic feet of single use medical products. In addition to gamma there are an estimated 41 electron-beam facilities around the world which sterilize low density products amounting to, approximately 7-10 % of all medical products currently being radiation sterilized.
It should be noted that when comparing aseptic processing to terminal sterilization, regulators have from time to time indicated that wherever possible terminal sterilization is preferred, because it lowers the chance of error, and risk of a contaminated product causing infection, or transmitting a disease to the patient. There is therefore both a strong technical and economic incentive to determine if ionizing radiation can be utilized for the terminal sterilization of many of the new or next generation drug-device combination products and to what extent the current infrastructure of irradiation facilities can accommodate this growing need.
To examine the issues associated with the sterilization of drug device combination products the International Irradiation Association (iiA) sponsored three Workshops one in San Diego, CA, USA in December 2006, and one in Washington DC, USA in June of 2007, and a recent on in London, England in September 2008 to review the technical and process challenges associated with the potential use of ionizing radiation for the terminal sterilization of combination drug-device products. These iia-organized Workshops succeeded in gaining both industry and US FDA support.
One concern is that in general because the efficacy of drug or biologic molecules is adversely affected when setting doses that achieve an SAL of 10-6 every effort must be made to determine the lowest possible dose required to make products "safe for their intended use" as distinct from achieving the currently required but arbitrary SAL of 10-6
The current sterilization dose setting guidelines of the International Standards Organization (ISO) and the Association for the Advancement of Medical Instrumentation (AAMI) have proven over time to be reliable in establishing the sterilization dose for a wide range of single use medical devices. In the case of medical devices to be labeled sterile regulatory authorities (in most cases) require the high radiation doses associated with achieving an arbitrary SAL of 10-6.
As stated in the AAMI Document ST 67 Sterilization of medical devices - Requirements for products labeled sterile, "So far there has never been a relationship established between the particular SAL of a medical product and hospital acquired (nosocomial) infections". In reflecting upon the determination of appropriate sterilizing doses, mindful of the fact that SAL levels of 10-3 & 10-4 are commonplace for vaccines and other pharmaceutical products produced by aseptic processing, and given the fact that drug molecules are generally radiation sensitive, it is an opportune time to take a more scientific approach to the selection of SAL's that when used in conjunction with current rational dose setting procedures will result in the establishment of sterilization doses that will render products "safe for their intended use", but not in excessive overkill.
Accordingly at the June 2008 meeting of AAMI WG-90 in Washington the iiA requested that the assembled experts undertake a work item to develop an approach to the choice of SAL that will more closely result in the selection of radiation sterilization doses that render products safe for their intended use, rather than to achieve the arbitrary SAL of 10-6 (a number established many years ago by the food industry).
Prior to the meeting in order to gather support for the proposed initiative iiA sponsored a wide-scale industry survey the results of which indicated that:
• 134 (99.4%) of 144 companies responding to the survey indicated support for the proposed work item
• 118(80%) of the 147 responding indicated that their current radiation sterilization requirements would benefit form the wider dose range resulting form the establishment of lower minimum doses.
• 101 (69%) of 147 respondents have products that cannot currently be radiation sterilized because of unacceptable physical material degradation at the sterilizing doses required in order to achieve an SAL of 10-6
(Survey Results)
As a result the AAMI WG90 approved the proposed Work Item and the needed task force has been established to examine this issue.
Additionally as a contribution to the Work Item a group of 8 authors agreed to update a paper published in 1993 entitled "Sterility Assurance and safety Assurance"
It was recognized with respect to this critical and far reaching issue that our industry through its trade associations must work closely from the outset with appropriate representatives from the regulatory authorities. We are pleased therefore that the US FDA / CDER/ OPS have agreed to actively participate on the recently formed AAMI SAL task force.
To begin with we are focusing on the USA, however many benefits exist to those products being developed around the world to allow fragile or radiation-sensitive products to be terminally sterilized. The convergence of the drug and medical devices sectors, and a choice of sterility assurance level based on patient safety and sound scientific principles, could enable the development of new transformational healthcare product (drugs, biologics, microelectronics, nanotechnology...). And potentially lower the required sterilization dose by up to 30% to 50% or more.
Presentations from the third iiA-sponsored workshop the 2008 September 25 meeting in London are contained in the iiA members-only sterilization section. Below are presentations from the first two workshops San Diego and Washington.
John Masefield, iiA Chairman and Executive Advisor, STERIS Isomedix, 21 June 2007 | John Masefield is the Chairman of the Board for the international irradiation Association (iiA). He leads a diverse, and duly elected Board with representatives from North America, Europe and Australia. With his leadership iiA is creating a strong, united, global voice to effectively and quickly deal with the challenges facing our industry, and to take advantage of opportunities to assist and promote the safe use of radiation processing.
David Liu, Vice President, Johnson & Johnson, Corporate Sterile Process Technology, USA , 21 June 2007 | David Liu is currently the Vice President for Johnson & Johnson, Corporate Sterile Process Technology Department. He is responsible for worldwide sterilization and aseptic process development, equipment and facility engineering design & validation, technology transfer, regulatory/compliance approval and related supply chain management.
Barry Parsons, Ph.D., Professor of Biochemistry, Leeds Metropolitan University, 21 June 2007 | Dr. Parsons is currently Professor of Biochemistry in the Faculty of Health at Leeds Metropolitan University in the UK. Previously, as a consequence of the growing international interest in free radicals, he became involved centrally in the development of a European Free Radical Research Facility (FRRF) at the Paterson Institute for Cancer Research- facilitated by the award of a major European grant. A further award in 2003 brought about the re-location of the FRRF to the Central Laboratory of the UK Research Councils, Daresbury, Warrington. Dr Parsons is currently Chairman of the FRRF Steering Group.
Ellis Kempner, Ph.D., Former Section Head of Macromolecular Biophysics Section NIH -NIAMS (National Institute of Health), 21 June 2007 | Dr. Kempner was the Section Head of Macromolecular Biophysics in the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institute of Health (NIH). He recently celebrated his many accomplishments during an outstanding 47-year government career. Studies of the direct action of ionizing radiation have been the focus of Kempner's research for many years
Byron J. Lambert, Ph. D., Advisor Sterilization and Material Engineering, Abbott Vascular, 21 June 2007 | Since 1990 Byron Lambert has held various positions at Abbott Vascular (previously ACS/ Guidant) and currently is Fellow, Sterilization Science. Responsibilities include member of the development teams to understand the compatibility of pharmaceutical agent in combination devices with ethylene oxide and electron beam sterilization. He has coordinated worldwide sterilization resources at Guidant to increase compliance, reduce sterilization cycle times and better manage costs. Bryon was responsible for the installation of two electron beam systems.
Martell Winters, Study Director & Consultant, Nelson Laboratories, Inc., 21 June 2007 | Martell Winters has been at Nelson Laboratories for over thirteen years and spent most of that time heading the Radiation Sterilization group, responsible for bioburden testing, bacteriostatsis and fungistasis (B/F) testing and radiation validation studies. He is currently a Study Director and Consultant where he spends most of his time supporting customers with validation issues, dealing with test of sterility failures and investigating bioburden problems and recommendations for corrective actions.
Bob Morrissey and Cathy Nutter, 21 June 2007 | Bob founded and headed the Johnson & Johnson Sterilization Science & Technology department for 22 years. This included worldwide process development and technology support programs in sterilization science and engineering, packaging, microbiology, and aseptic pharmaceutical operations. Cathy recently retired as a microbiologist and scientific reviewer in the Office of Device Evaluation (ODE), Center for Devices and Radiological Heath (CDRH), U.S. Food and Drug Administration (FDA).
Hussong, Ph.D., New Drug Microbiology Team, Office of Pharmaceutical Science, CDER, FDA, 21 June 2007 | Dr. David Hussong is the Associate Director for New Drug Microbiology in the Office of Pharmaceutical Science in the Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER). He directs the CDER team that performs the review of microbiological quality aspects described in the Chemistry, Manufacturing and Controls technical section of drug applications. His research experience includes studies of Salmonella and Legionella and development of methods for their detection, and development of immunologically-based diagnostic tests for mycobacterial infections.
John B. Kowalski, Ph.D., President, microGAMMA, LLC, 22 June 2007 | Over the past 28 years, Dr. Kowalski has worked in the areas of absorbable medical devices, sterilization microbiology, and sterilization process development and validation. His key projects have included biological indicator development and sterilization process development and validation with moist and dry heat, ethylene oxide, radiation, hydrogen peroxide gas plasma, and gaseous chlorine dioxide. He has authored numerous articles in the area of sterilization science and technology and is the originator of the VDmax methodology for the establishment of a radiation sterilization dose for medical products.
Eric Beers, Director of Engineering, MDS Nordion, 22 June 2007 | Eric Beers is the Director of Engineering at MDS Nordion, a world leader in the supply of gamma sterilization systems. Mr. Beers has more than 25 years of experience in irradiator design, manufacture, installation, facility maintenance and operations worldwide. He has a rare combination of engineering design, operations know-how and customer requirement insights.
Barry Fairand, Ph.D., Senior Consultant Radiation, Sterigenics, 22 June 2007 | Barry Fairand is a consultant to the radiation processing industry, with more than 36 years of professional experience in the field of scientific research and radiation processing of materials, medical devices and critical health care products.
Michael C. Saylor, President, Special Process Services, L.C., 22 June 2007 | Michael Saylor operates Special Process Services, L.C.; a consulting firm specializing in radiation treatment and sterilization processes involving radioisotopes (Cobalt-60, Caesium -137), accelerated electrons (0.1 - 12 MeV) and X-rays. His current vocational efforts are in the areas of mathematical modeling of radiation processes, high-power X-ray (bremsstrahlung) applications, process design/control/validation and training course development/delivery.
John Masefield and Ruth Brinston, published in Medical Device Technology (MDT) March/ April Issue | On December 6, 2006 pharmaceutical, biotech, medical device manufacturers and radiation processing experts came together in La Jolla, San Diego California at a Workshop sponsored by the international irradiation Association (iiA) to explore scientific advances, future technical challenges and practical aspects of the radiation sterilization of advanced combination drug-device products. Combination products are comprised of more than one type of regulated article or component (device, drug or biologic), and typically have more than one identifiable mode of action or therapeutic benefit.
John Masefield, Executive Advisor, STERIS Isomedix and iiA Chairman, 6 December 2006 | John Masefield, a leader and innovator, is one of the most influential pioneers in the field of radiation sterilization. Educated in engineering and physics in the U.K. In 1959, Mr Masefield joined Atomic Energy of Canada (AECL), later to become MDS Nordion, and worked on the development and establishment of the first industrial cobalt-60 irradiator in North America for the sterilization of medical devices
Barry Parsons, Ph.D. Professor of Biochemistry, Leeds Metropolitan University, UK, 6 December 2006 | Dr. Parsons is currently Professor of Biochemistry in the School of Health and Human Sciences at Leeds Metropolitan University in the UK. Previously, as a consequence of the growing international interest in free radicals, he became involved centrally in the development of a European Free Radical Research Facility (FRRF) at the Paterson Institute for Cancer Research- facilitated by the award of a major European grant.
Ellis Kempner, Ph.D. Former Section Head Macromolecular Biophysics Section, NIH- NIAMS, 6 December 2006 | Dr. Kempner was the Section Head of Macromolecular Biophysics in the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institute of Health (NIH). He recently celebrated his many accomplishments during an outstanding 47-year government career. Studies of the direct action of ionizing radiation have been the focus of Kempner's research for many years.
Dennis Jamiolkowski, Distinguished Research Fellow, Johnson & Johnson Ethicon, 6 December 2006 | Dennis Jamiolkowski joined the Exploratory Polymer Section of the Research Division of Ethicon, Inc., a Johnson & Johnson Company in 1974 shortly after receiving a B.S. in Honors Chemistry. He is a member of the Society for Biomaterials and is a former Chair of Johnson & Johnson's Council of Research Directors Polymer and Biomaterials Subcommittee. Dennis is a J&J Corporate Office of Science and Technology (COSAT) "Excellence in Science" Grant winner.
Suketu Desai, Ph.D. Principal Scientist, J&J Global Biologic Supply Chain, 6 December 2006 | Suketu Desai, Ph.D. is currently Principal Scientist in the Global Technical Services group at Global Biologics Supply Chain, LLC, which is a wholly owned subsidiary of Johnson & Johnson. His responsibilities include technical support for technology transfer, formulation development, and manufacture of late-stage and commercial biopharmaceuticals including monoclonal antibody/protein-based sterile lyophilized and liquid products. He also oversees project and portfolio management for the group.
Moderator- James Hauschild, Ph.D. Principal Scientist J&J Sterile Process Technology, 6 December 2006 | Dr. Hauschild has worked for Johnson & Johnson for the past 10 years and is currently a Principal Scientist at J&J Sterile Process Technology (SPT). The mission of SPT is to provide sterilization science, engineering, operations, and aseptic processing expertise to Johnson & Johnson operating companies around the world to deliver products of the highest quality at the lowest cost. His past research interests included chlorine dioxide sterilization and biological indicator development.
David Liu, VP- J&J Sterile Process Technology, 6 December 2006 | David Liu is currently the Vice President for Johnson & Johnson, Corporate Sterile Process Technology Department. He is responsible for worldwide sterilization and aseptic process development, equipment and facility engineering design & validation, technology transfer, regulatory/compliance approval and related supply chain management.
Barry Fairand, Senior Radiation Consultant, Steripro Services, Sterigenics, 6 December 2006 | Barry Fairand is a consultant to the radiation processing industry, with more than 36 years of professional experience in the field of scientific research and radiation processing of materials, medical devices and critical health care products.
Eric Beers, Director Engineering, MDS Nordion, 6 December 2006 | Eric Beers is the Director of Engineering at MDS Nordion, a world leader in the supply of gamma sterilization systems. Mr. Beers has more than 25 years of experience in irradiator design, manufacture, installation, facility maintenance and operations worldwide. He has a rare combination of engineering design, operations know-how and customer requirement insights.
Moderator- Lisa Foster, VP Steripro Services, Sterigenics, 6 December 2006 | Since 1989 Lisa Foster has held various quality assurance positions at both the facility and corporate levels at Sterigenics. In 2004, she was promoted to her current position as Vice President of SteriPro Services, a division of Sterigenics. Her areas of expertise include sterilization validation, regulatory compliance, irradiator qualification, quality system regulations, radiation safety and quality systems management