The drug industry is now deep in the waters of track-and-trace (TnT) for chain-of-custody security and validation of its products. And because counterfeiting has been principally the bane of drugs, not devices, the device industry has had little reason to venture into the world of radio frequency identification (RFID) and other methods of securing the supply chain. However, TnT clearly is drawing near for makers of both devices and diagnostics.

The FDA last month issued a statement asking for input on how a unique identifier system might be structured for devices. The FDA said that such an identifier could make recalls easier, reduce medical errors, and improve adverse event reporting.

While the FDA and the drug industry seem to have settled on RFID technology for tracking, the agency’s announcement mentions that both RFID and bar codes are among the technologies that are under consideration to augment paper records. Daniel Schultz, MD, director of the agency’s Center for Devices and Radiological Health, reiterated the underlying logic by saying that “a unique device identifier [UDI] system could have broad applications in reducing medical errors, facilitating device recalls, improving medical device adverse event reporting and encouraging cost effectiveness by improving delivery and supply chain efficiency.”

The notice discusses an April 2005 meeting hosted by the Food and Drug Law Institute (FDLI; Washington) that drew comments from a number of stakeholders. According to the FDLI report, some of the pitfalls associated with any TnT system would include the potential for radio frequency (RF) interaction with hospital equipment and the logistics of “developing an infrastructure to handle the data,” a concern that also came up during drug TnT talks.

The agency indicated that it will work with other federal parties in this pursuit, including the Centers for Medicare & Medicaid Services (CMS; Baltimore) and the Agency for Healthcare Research and Quality (Washington) to find out what issues they might have with device TnT. Andrew von Eschenbach, acting FDA commissioner, chimed in as well, remarking that the agency wants to beef up post-marketing data collection as part of a “total product lifecycle ap-proach to how we look at medical devices ... focusing more attention on the kinds of systems and processes we need to have in place to monitor products after they are approved.”

The FDA’s Federal Register notice suggests that any rollout of TnT for devices could incur downstream regulatory liability for device and diagnostics makers. The proposed data set for device identification includes the manufacturer, make and model as well as “unique attributes (e.g., size, length, quantity, software version).” The notice says that “a change to any of the above criteria would likely necessitate a new UDI,” even changes such as “different size or length catheters of the same type.”

In a statement, Stephen Ubl, president/CEO of the Advanced Medical Technology Association (AdvaMed; Washington), said that he is “encouraged that FDA is taking a methodical approach to exploring the feasibility and utility of a unique identifier system” and is pleased that the agency seems uninterested in a “one-size-fits-all approach.”

Ubl added that while the industry sees the value in a UDI system, AdvaMed is of the opinion that mandatory identifiers “should only be required where there is a clearly defined patient safety issue ... as was the case with the mandatory bar code rule for drugs.” He noted that “devices are extremely variable in size, shape and materials ... and do not lend themselves to a single method of identification.”

HIT sharing final rules soon to go into effect

The Department of Health and Human Services (HHS) has finished its work on final regulations to allow doctors’ offices to boost their health information technology (HIT) systems with the help of hospitals and other entities. Thanks to the Medicare Prescription Drug, Improvement and Modernization Act of 2003, physician practices that cannot afford to purchase updates for hardware and software can now accept assistance from hospitals and other donor organizations in the pursuit of implementing electronic health record (EHR) systems and electronic prescribing (e-prescribing). HHS Secretary Mike Levitt said that the final rules -– to take effect about Sept. 30 – should “help physicians get these systems in place and working for patients faster.”

According to a press statement, both the HHS Office of Inspector General (OIG) and CMS have published documents to address their responsibilities in this endeavor. Many of these regulations are scheduled to expire on Dec. 31, 2013. (President George Bush’s 2003 call for adoption of electronic health records recommended that the task be completed by 2014.) One exception to the safe harbor expiry is donations of e-prescribing technology.

The CMS rules deal with the self-referral dilemma implicit in any HIT donor/donee relationship. Up to now, doctors could not refer patients to hospitals and other entities for so-called designated health services (DHSs) when a financial relationship existed. The law also banned the practice of billing CMS for such referrals as a Medicare service.

The OIG rule established a pair of new safe harbors under existing federal anti-kickback statutes, specifically allowing donor hospitals and other entities to provide doctors’ offices with e-prescribing and EHR technologies. To qualify for the safe harbor, any donated hardware or software must offer interoperability, a feature that has long been a sticking point in efforts to bring various segments of the healthcare industry into the information age.

For its part, OIG informs interested parties that they can “use the OIG advisory opinion process ... to determine whether their particular arrangements would be subject to OIG sanctions.” OIG also advised that “arrangements that do not comply with the electronic prescribing safe harbor ... will not necessarily be illegal under the anti-kickback statute.”

Among the expectations of e-prescribing is that physicians and pharmacies will be able to more readily substitute generic drugs and other alternatives to a prescribed medication, which, it is hoped, will drain off some of the impetus behind the ongoing rise in healthcare costs.

Another hoped-for benefit is that medical errors will be reduced significantly, thanks to the lower error rate of electronic information exchange as compared to hand-written records and prescriptions. The size of the “paperwork” component of administrative work may also shrink with the increased use of computer technology.

Many observers see problems with privacy in the increased use of computers in healthcare, but such concerns are not universal. In testimony at a June 21 hearing before the Senate Commerce, Science and Transportation Committee, Mark Leavitt, MD, chairman of the Certification Commission for Healthcare Information Technology, said that privacy concerns are “a knee-jerk reflex.” He argued that Internet purchases are an everyday event and that while “paper cannot tell you who has looked at it,” audit trails can identify observers of files, even on the Internet.

CMS Administrator Mark McClellan said that the HIT rules “will improve care by giving doctors and other healthcare providers needed support for interoperable health records that enable them to increase quality and improve efficiency.” He also remarked that Medicare “plays a critical role in this important initiative, and we are committed to its success.” The OIG final rule calls for recipients to contribute at least 15% of the cost of the EHR technology items and related services. However, donees are not required to incur any costs in connection with e-prescribing technology.

Tom Leary, director of federal affairs with the Healthcare Information and Management Systems Society (HIMSS; Chicago), told Biomedical Business & Technology: “We’re pleased that the government has released the regulations expanding Stark and anti-kickback exemptions with a general focus on e-prescribing and electronic health records. We’re reviewing the changes in the final rule and look forward to evaluating the impact on all our members, both end users at the hospitals and vendors as well.”

Pushing personalized medicine

The FDA had some words of advice for attendees at the American Association for Clinical Chemis-try’s (AACC; Washington) 2006 annual meeting in Chicago on the challenges of biomarker and drug co-development and regulation – commonly known as the path to “personalized” medicine. While saying that the “diagnostic lifecycle is by now well-defined,” Steven Gutman, MD, of the FDA’s Center for Devices and Radiological Health, advised companies that if they have an assay that they “think is good,” then certainly pursue studies that, with any luck, will have clinical significance and will ultimately be reimbursed.

He noted the importance of co-development in which biomarkers are used both for diagnosis and drug development, with diagnostics a key vehicle for improving a drug discovery pipelines. However, he warned, the drug can become “hostage” to the device in the co-development process, meaning that there needs to be a balance between drug and device, and “safety and effectiveness have to be [determined] in both.” He also said that the “whole notion of personalized medicine” is perhaps oversimplified in the way that it currently is discussed, because often omitting the complications of the required regulatory processes in-volved.

There are two ways of credentialing diagnostics and drugs in co-development: first identify the pati-ents affected or “recruit and treat" according to the biomarker of interest. “In my view, the ideal is a matrix of all patients,” he said. Secondly, studies for a diagnostic could be done in a way in which a drug is working in a subset of patients, but Gutman said he is “not aware of any submissions on this predicate.”

To determine the timing of a diagnostic study, Gutman said it is “optimal” if the diagnostic study and the drug study are coordinated. If the studies cannot be conducted simultaneously, then Gutman suggested saving the samples from one study for use in the other. He acknowledged that there is “little regulatory or scientific history” on which to base questions of biology when co-development is approached, which ultimately means that “for companies, there are probably financial risks as well.”

However, the scientific “literature is growing,” he said. For instance, the FDA is developing an updated concept paper on co-development which should help with a roadmap for companies wishing to pursue this avenue. And, Gutman said, the CDRH and the FDA’s Center for Drug Evaluation and Research (CDER) “work together well.” In a comment obviously res-ponding to persistent criticisms of the agency, he said: "Our purpose is to protect the public’s health ... you can firebomb the FDA, and you can get rid of us, but those ... pesky questions will stay on the table.”

Representing the CDER, Felix Frueh, MD, associate director of genomics at the FDA, told the audience: “Pharmacogenomic-based drug therapy is only possible if we have two things: a drug and a diagnostic” – and with information about both. “It is valuable in the marketplace also only if we know these two things,” he said. Frueh said the FDA is in the process of developing a web site on the genomics side of the equation. It will list biomarkers and drugs, so companies can conduct more complete searches as they ramp up development.

He pointed also to a proposal on biomarker validation, to be published soon, that will “discuss the validity of preclinical genomic markers” for drug safety. The goal of this and other initiatives is to create “regulatory buy-in.” As to the why of drug/test co-development, Frueh said the primary goal of this approach is to move therapy from a trial-and-error approach to a scientifically based foundation for drug efficacy.

FDA to develop nanotech task force

The FDA last month unveiled plans to develop a Nanotechnology Task Force, charged with determining regulatory approaches that encourage the development of FDA-regulated products that use nanotechnology materials. The agency said that the task force “will identify and recommend ways to address any knowledge or policy gaps that exist so as to better enable the agency to evaluate possible adverse health effects from FDA-regulated products that use nanotechnology materials.” It said it will address these “product-specific ... issues on an ongoing basis.”

The task force will:

• Chair a public meeting Oct. 10 to help FDA further its understanding of developments in nanotechnology materials, including issues pertaining to biological interactions leading to either beneficial or adverse health effects.

• Assess the current scientific knowledge concerning nanotechnology materials for carrying out the FDA’s mission.

• Evaluate the effectiveness of the agency's regulatory approaches to meet any challenge presented by the use of nanotechnology materials in FDA-regulated products.

• Explore opportunities to foster innovation using nanotechnology materials to develop drugs, biologics and devices, and to develop safe foods, feeds and cosmetics.

• Strengthen FDA’s relationships with other federal agencies, and international regulatory bodies, professionals and other stakeholders to gather information regarding nanotechnology materials.

• Consider vehicles for communicating to the public concerning issues in nanotechnology.

The task force will be required to submit its initial findings and recommendations to Andrew von Eschenbach, MD, acting FDA commissioner, within nine months after the Oct. 10 meeting.

Consensus on potential biothreat powders

Federal, state and local agencies have reached consensus on the first validated national standard for collecting, packaging, and transporting samples of visible powders that are suspected of being biological threat agents, such as anthrax. The new standard meets the needs of first responders to test powders on site, and the needs of the federal agencies to conduct tests on the same, uncontaminated powder samples for forensic and confirmatory analysis.

The national sample collection procedure was developed and approved by AOAC International, a facilitator for developing analytical standards. The new standard is applicable to nonporous surfaces only and incorporates reference guidance for packaging and transport of suspicious powders to comply with all appropriate federal regulations regarding biosafety and biosecurity.

The development and testing of the standard were supported by the Science & Technology Directorate of the Department of Homeland Security in response to a need for a coordinated effort with federal agencies and emergency responders to standardize activities related to anthrax and other biological agent incidents.

The purpose of the sampling procedure is to have a standard to be followed by emergency responders for suspicious powder collection in order to reduce exposure risks, reduce the variability associated with sample handling and analysis and increase the reliability of sampling visible powders from nonporous surfaces.

Emergency responders need to sample a suspicious powder in order to do a presumptive analysis. Federal agencies also need a sufficient quantity of the powder to do confirmatory testing. The new method provides both groups with sufficient powder to perform their tests in a manner that protects the powder from contamination. Training emergency responders who collect and disseminate the powder is planned.

“The development of a national standard for the collection of suspicious powders is an important step forward,” said Chief John Eversole (Ret), chairman of the International Association of Fire Chiefs’ Hazardous Materials Committee. “This standard provides a uniform and systematic procedure whereby accurate, presumptive information can be determined by the first responders and ensure the preservation of sample evidence for confirmatory analysis and criminal prosecution. Our next step must be to broaden the scope to do sampling in other situations.”

The standard developed by AOAC has been published by ASTM International (www.astm.org).

Two groups issue guidelines on consciousness

Aspect Medical Systems (Newton, Massachusetts) said that the Australian and New Zealand College of Anesthetists (ANZCA) and the Madrid Centro Society for Anesthesia (MCSA) have each published recommendations for monitoring level of consciousness during anesthesia. The recommendations were written to guide ANZCA and MCSA members in recognizing the problem of unintended awareness and adopt a consensus on how to reduce the incidence of inadvertent surgical wake-ups. Aspect noted that unintended awareness occurs when patients do not receive enough anesthesia, leaving them at risk for becoming aware of what is happening and remembering this experience after the surgery is over.

“The ANZCA and MCSA recommendations are consistent with the clinical guidance provided by other medical societies in the U.S. and Europe and reflect an increasing global recognition of the need to address awareness as a patient safety concern,” said Nassib Chamoun, president/CEO of Aspect. “We believe this is an important step toward improving patient safety and reducing the risk of awareness.”

He said that Aspect’s Bispectral Index (BIS) “is the only brain monitoring technology or clinical intervention that has been shown in large scale, prospective clinical research to reduce the incidence of awareness.” Using a sensor placed on the patient’s forehead, BIS monitoring translates information from the electroencephalogram into a single number that represents each patient’s level of consciousness. This number – the BIS value – ranges from 100 (indicating an awake patient) to zero (indicating the absence of brain activity). Using the BIS value allows clinicians to make better-informed decisions to achieve optimal anesthesia, the company said.

The ANZCA has said that consciousness monitors should be used in all high-risk anesthetics and that equipment to monitor the anesthetic effect on the brain should be available for use on patients at high risk of awareness during general anesthesia. For its part, the MCSA said that it promotes the use of depth-of-consciousness monitors and supports education on how to best use the monitors to reduce the incidence of intraoperative awareness. The society defines preventative measures that apply to the clinician, the equipment, the medical staff, and the patient, identifying a list of high-risk patient characteristics.

To date, Aspect’s BIS technology has been used to assess more than 16.3 million patients.