Medical Device Daily Washington Editor

The Oct. 10 warning letter to LifeCell (Somerville, New Jersey), did not sit in the bin for long at FDA, making its way into print the month following the end of the inspection, which ran between the months of June and September. The maker of the Strattice, a reconstructive tissue matrix, did not fare well in its responses to the inspectional form 483, getting a passing grade for none of the six findings detailed in the warning letter. In one instance, FDA noted that further information was needed to evaluate the company's proposed corrections, but the responses for the other five were all deemed inadequate.

The heavily redacted warning letter omits a substantial amount of information dealing with LifeCell's production of the Strattice, a reconstructive tissue matrix, but the last of the six citations notes that six lots of the Strattice produced in January "failed endotoxin testing" in connection with equipment that bore "significant" endotoxin levels. However, the other citations dealt with, among other things, environmental monitoring and corrective action, although redactions made it difficult to ascertain whether endotoxins were at the root of some of the other findings.

The warning letter led with a citation that states that LifeCell "failed to identify and validate" a redacted element of the process, then states that LifeCell "failed to adequately validate the primary packaging procedure for the Strattice."

This citation included the finding that "the potential sealing problems occurring due to [redacted] are not documented in the device history records" and that "your firm is not trending the number of [redacted]."

The warning letter states that the company's response to this finding was inadequate because LifeCell did not "identify the root cause (e.g., operator error or a possible process problem)" and because the response did not "provide any evidence that the corrective actions taken ... were verified or validated to ensure that such actions are effective and do not adversely affect" the device. FDA requested that the company provide the agency with updated procedures, which will be reviewed on the next inspection.

The second citation, which was listed as a problem with corrective and preventive action (CAPA) states that that company's quality investigation procedures indicated that "if a relatively simple corrective and preventive action is required, the action may be documented on the original document" instead of with a CAPA report. This citation describes an incident dated Feb. 12, 2008 in which a deviation report requested "a waiver for six lots of Strattice" that were "approved for release and further processing without any form of corrective action after biochemical testing was performed" on three of the six. Another incident in April involved seven lots of Strattice for which "no formal corrective action was required because the testing previously performed" in connection with the incident in February "demonstrated that the product was not affected" by the incident. The description of the nature of that incident was redacted.

Again, LifeCell's proposed fix was deemed inadequate because the revised procedure "still allows corrective and preventive action to be performed without verifying or validating the actions."

Other citations include one for employee training for clean room cleaning operations, the response to which was found adequate "if they are properly implemented." However, the following citation made note of environmental monitoring procedures that did not include supporting data.

Kristie Madara, spokeswoman for Kinetic Concepts (San Antonio, Texas), the firm that owns LifeCell, told Medical Device Daily, "we are in the process of communicating with FDA to address the issues outlined in their letter and we fully expect we can implement the corrective actions required." She also said that the issues were related to quality systems and not "the safety and efficacy of our products."

PTO implements WIPO patent rule

The World Intellectual Property Organization (WIPO; Geneva) updated last year the way it deals with the filing of patent applications that would claim priority over previously filed applications by extending the priority period from 12 to 14 months under some circumstances. According to an advisory published by the law firm of Alston & Bird (A&B; Atlanta), the U.S. Patent and Trademark Office has now amended its rules to comply with at least part of the WIPO rule.

According to the Nov. 4 A&B advisory, an international application filed under the Patent Cooperation Treaty (PCT) – which was signed in 1970 and modified on three occasions since – "cannot claim priority to a previously filed U.S. application (provisional or non-provisional) unless the international application is filed within a year of the filing date of the U.S. application." Thanks to the new rules, this window can be extended for two additional months so long as "the delay occurred in spite of due care and/or the delay was unintentional."

Any entity wishing to file for the two-month extension will have to cough up a bit more than $1,400 and will also have to produce a statement "that the delay in filing ... was unintentional," although PTO apparently has reserved the right to "require additional information if there is a question" as to the veracity of the claim that the delay was indeed unintentional.

As yet, PTO will not employ both "unintentional" and "despite due care" standards because of conflict with U.S. law.

Scott Brient, an attorney in the patent section at A&B, told Medical Device Daily that the standard for "unintentional" is indeed not stringent at all. "You typically don't need to document it, they'll take your word for it," he said. As for what sort of corroborating information PTO might want, he said "any information you could come up with" would suffice, including any correspondence that has passed between company personnel on the subject.