During the course of 19 months, FDA inspected Steris Corp. twice and issued a warning letter to the company to cease marketing the Steris System 1 (SS1) sterile processing system, which Steris failed to do. In response to that failure, FDA issued a letter to healthcare facility administrators and infection control practitioners saying that they should switch to alternative, legal sterilization and disinfection systems.

According to FDA, this was a step that the company had said that it would take voluntarily 19 months before. Based on an inspection in May 2008, FDA determined that the SS1 had been so significantly modified that it was now adulterated and misbranded, and therefore illegal. But FDA says that Steris delayed by seven months a commitment it made to notify SS1 customers and users about FDA’s concerns and to advise them, in FDA’s words, that they should transition to a legally marketed alternative.

Still far short of that commitment much later, Steris’s Web site was still describing the SS1 in mid-December 2009 as
“the proven, low-temperature sterile processing system for immersible surgical and diagnostic devices. Even delicate, heat-sensitive scopes, cameras, instruments, and accessories can be safely sterile processed in 30 minutes—just in time (JIT) for each procedure.” The site was offering the device for sale “in the U.S. on a ‘one for one’ replacement basis only. Steris,” it said, “will continue to support System 1 for at least two years from the date of the notice with the sale of all accessories, Steris 20 sterilant, service, parts, and replacement units.

“Steris,” it continued, “has submitted a 510(k) premarket notification for an updated System 1, which is currently under review by FDA. Steris will work with our customers on a timetable to transition to the purchase of a replacement.”

Apparently, the company was not getting into the spirit of FDA’s intentions, and a second inspection by the agency found
Steris had not, in FDA’s strained words, “been working effectively to transition its customers to replacements for the SS1.” That’s when FDA decided to go directly to the company’s customers and SS1 users, issue a news release, and open detailed Web pages about the problem on the agency’s Internet site.

The agency’s online notice, signed by CDRH compliance director Timothy A. Ulatowski, spoke of “some reports of malfunctions of the SS1 that had the potential to cause or contribute to serious injuries to patients, such as infections…” and “reports of injuries, mostly burns from exposure to the sterilant solution.” However, FDA apparently felt it did not have enough to go on to support conventional legal action—i.e., product seizure and a federal court complaint for injunction restraining Steris from its continuing defiance.

On the surface, the situation stands in sharp contrast to the civil money penalties action FDA took against the arguably similarly defiant manufacturer of temporomandibular joint implants, TMJ Implants Inc. (TMJI). It might be observed that unlike the Steris case, TMJI’s situation involved alleged adverse-event reports about a Class III implant, rather than a mere 510(k)-level sterilizing system that had been modified without FDA’s consent.

Still, the unusual approach to Steris’s disobedience bared some FDA teeth that are seldom seen in public, teeth that may provide the agency with swifter and more effective results in future enforcement actions than conventional redress to seizure and injunction. By going directly to a balky firm’s customer and user base, FDA is spared the delay inherent in preparing litigation strategies that meet Department of Justice standards—although in FDA parlance, delay is a relative term when you consider that it took the agency nearly a year to implement its response to Steris’s defiance.

Steris’s spokesperson Stephen Norton says that “daily conversations are under way with FDA to reach a resolution to the regulatory matter that is in the best interest of [our] customers.” Norton encourages customers to visit www.steris.com to learn more information about the issue.

How much notice should other companies take of FDA’s unusual action in this case? In a prepared statement, Ulatowski said rather stiffly that “the agency will use the enforcement tools at our disposal to help protect the public health from medical devices violating the law.” He went on to say that

TMJI Seeks En Banc Review of Court Defeat

Device maker TMJI and its president have petitioned the U.S. 10th Circuit Court of Appeals for an en banc (all 12 judges) review of their appellate loss last October to FDA. The company is arguing a within-circuit decisional conflict, denial of “substantive due process” at FDA, and agency failure to meet its own civil money penalties burden-of-proof requirements. The three-judge unanimous ruling in October 2009 endorsed FDA’s $340,000 civil money penalties imposed for failure to file 17 medical device reports (MDRs) involving the company’s temporomandibular joint implants, effectively affirming that the agency has the last word in interpreting its own regulations.

In their 18-page request for en banc review, TMJI and president Robert W. Christensen contend that the appellate panel’s decision “conflicts with and ignores the prior recent decision in this circuit of the federal district court for the State of Utah…that was involved with the issue of how broad a latitude FDA should be given in the interpretation of its published written policies applicable to companies it regulates.” This 2005 case, U.S. v. Utah Medical Products, has since been written out of FDA enforcement history. It established that in QSR and GMP compliance, FDA may not prescribe how industry is to reach compliance (“many roads lead to Rome”).

FDA argued in the TMJI case that the Utah case was too different to be relevant. However, both in their appeal to the 10th Circuit and in their request for en banc review, TMJI and Christensen persist in their contention “that the court’s decision in Utah Medical be considered as controlling precedent for evaluation of the MDR regulations at issue in this [civil money penalties case].”
On due process, the petitioners contend that the three-judge panel “ignored completely” their “indisputable facts of record” on a “process failure” in the handling of the case at FDA—a failure that had been admitted to two Congress members by former commissioner Andrew von Eschenbach. This involved alleged preparation of the civil money penalties case while the agency mislaid TMJI’s appeal to the commissioner for eight months, a process the petitioners have called an “ambush” and “treachery.” Citing criteria established in a 1976 Supreme Court case, Matthews v. Eldridge, they say they “never received any real substantive due process at the administrative level.”

Regarding FDA civil money penalties burden-of-proof requirements, the petitioners allege that the agency failed to meet—and that the appellate judges ignored—the requirement of CFR part 17.33 that there be a “preponderance of evidence.” In nine of the 17 events, FDA redacted device-identifying information, the petitioners say, contending that nowhere in the underlying statute or in the MDR regulations is there legal justification for the panel’s interpretation—i.e., “that in such situations, MDRs are required even though the device was not the ‘cause in fact’ or even though there is not enough evidence to support a conclusion that the device caused or contributed to a serious injury.”

Endotec Cited for QSR Violations on Implant Production

In December, FDA released a warning letter to Endotec Inc. that resulted from an inspection last May at the company’s Orlando, FL, orthopedic implant manufacturing facility. The inspection revealed multiple violations of FDA’s quality system regulation (QSR). According to the letter from FDA’s Florida district office, observations listed on an FDA-483 included:

?    Failure to review, evaluate, and investigate complaints involving the possible failure of a device, labeling, or packaging to meet any of its specifications unless such investigation has already been performed for a similar complaint, and another investigation is not necessary.
?    Failure to develop, conduct, control, and monitor production processes to ensure that a device conforms to its
specifications.
?    Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements.
?    Failure to establish and maintain procedures to control the design of the device to ensure that specified design requirements are met.
?    Failure to establish procedures for quality audits and to conduct such audits to ensure that the quality system is in compliance with the established quality system requirements and to determine the quality system’s effectiveness, with quality audits conducted by individuals who do not have direct responsibility for the matters being audited.

The letter said the adequacy of responses Endotec made to these observations could not be determined because they lacked sufficient details on steps the company planned to take to address the issues, and there was no supporting documentation of the steps taken or planned.

Endotec was told to take prompt action to correct the violations (see the sidebar “Endotec: Corrections and Removals”) and to respond with a listing of specific steps taken. The firm’s response must include an explanation of how the company plans to prevent these or similar violations from occurring again. FDA also requested documentation of the corrective actions with a timetable for their completion.

Stryker Recalls Surgical Navigation Device

CDRH reported in December that Stryker had recalled its Operating Room System II Surgical Navigation System. A recall notice says that the device is a computer-aided surgery platform that surgeons use to perform hip, knee, spine, neurology, and ear, nose, and throat surgery. The product was manufactured from March 31 through July 16 and distributed from March 31 through July 28 of last year.

The October 26 Class I recall was initiated because the device may suddenly stop working, CDRH said, the screen may freeze, or the information may update very slowly. The problems may affect all software products used on the workstation. Such failures could result in surgery delays, risk of infection, increased disease symptoms, potential neurological problems, or injury due to the surgeon operating in an unintended area. Depending on the type of surgery, the notice said, the failures could lead to serious adverse health consequences, including death.

Swedish Imports by Abbott Medical Optics Blocked

FDA recently revealed that it was refusing to admit Healon D ophthalmic viscoelastic devices to the U.S. market. The products are made by Abbott Medical Optics’s Swedish subsidiary, AMO Uppsala, and the agency’s actions are due to a serious quality system violation found nine months earlier during an inspection at the firm’s manufacturing facility. A September 18 CDRH warning letter said that its “detention without physical examination” order would not be lifted until the firm’s violations were
corrected.

The letter said the inspection determined that the company failed to adequately ensure that when the results of a process cannot be fully verified by subsequent inspection and test, the process is validated with a high degree of assurance and approved according to established procedure. The firm “failed to perform and document equipment cleaning validation for production of Healon D ophthalmic viscoelastic devices,” CDRH wrote. The center said that the firm’s response to the FDA-483 was inadequate because the company did not intend to complete validation of the equipment cleaning process for producing Healon D ophthalmic viscoelastic devices for 10–15 months, pending completion of a root cause investigation from one Healon D lot that had been recalled.

The company was told to respond within 15 days with a list of specific steps taken to correct the violation, including an explanation of how it would prevent this and similar violations from occurring again. The company was also asked to submit documentation of the corrective action taken along with a timetable for completion. FDA said it would tell the company if its response was adequate and whether there was a need to reinspect the facility to verify that appropriate corrections have been made.

FDA Cites Centra Health IRB

An investigator from FDA’s Baltimore district office found “objectionable conditions” during a September 1–14 inspection last year of the Centra Health Institutional Review Board (IRB) in Lynchburg, VA, CDRH said in December. The inspection was conducted under a program intended to ensure that data and information in submissions for investigational device exemptions, premarket approval, and 510(k)s are scientifically valid and accurate. The inspections are also meant to ensure that human subjects are protected from undue hazard or risk during the course of scientific investigations.

A November 20 warning letter said that violations cited in an FDA-483 included the following:

?    Failure to conduct continuing review of research at least annually.
?    Failure to ensure that the IRB reviews proposed research at a convened meeting at which a majority of the members are present.
?    Failure to prepare and maintain adequate documentation of IRB activities, including minutes of IRB meetings.
?    Failure to have adequate written procedures governing IRB functions and operations.

According to the letter, Centra’s responses were inadequate in that they didn’t give specific action plans for correcting the violations and preventing their recurrence and didn’t document any changes made. The IRB was given 15 days to provide written documentation of actions that have been taken or will be taken to correct the noted violations and prevent recurrence of similar violations.

Medtronic Cardiac Rhythm Unit Gets Warning Letter

An FDA inspection last June at Medtronic’s Cardiac Rhythm Disease Management business unit in Mounds View, MN, found quality system violations in the firm’s manufacturing of implantable pacemakers and pacemaker leads. The agency recently posted a November 9 warning letter from its Minneapolis district office that says the violations included the following:

?    Failure to establish and maintain adequate corrective and preventive action procedures to ensure consistent handling of investigations of the cause of nonconformities relating to product, processes, and the quality system, and identification of actions needed to correct and prevent recurrence of nonconforming product or other quality problems.
?    Failure to follow procedures for validating or verifying design changes before their implementation.
?    Failure to implement procedures addressing documentation of corrective and preventive action activities.
?    Failure to establish and maintain adequate design validation procedures to include risk analysis.
?    Failure to implement procedures for document control.
?    Failure to establish and maintain adequate procedures for purchasing controls ensuring the type and extent of control to be exercised over the product.

The district office told Medtronic to take prompt action to correct violations addressed in the letter. It noted that company responses had promised corrective action but that several of the actions have not been completed. It said that the promised corrective actions appear to be adequate but a follow-up inspection will be needed to ensure that corrections are implemented and effective.

The letter also said that the inspection found deficiencies in MDRs, including failure to submit five reports within mandated time frames. Again, it said, the promised corrective actions appear to adequately address the deficiencies and will be evaluated during a follow-up inspection.