A Medical Device Daily

The quality of data backing a series of 510(k)s for a California diagnostics maker was called into question during a December inspection of W.H.P.M. (WHPM; El Monte, California), which found itself on the receiving end of a March 19 warning letter pockmarked with 14 citations. In FDA's view, the December inspection of the maker of assays for drugs of abuse provided "no assurance that the upper level of management, including the President, provides adequate control of the quality system," a finding that hinted at systemic troubles detailed elsewhere in the warning letter.

The inspection also apparently triggered a reconsideration of a pending 510(k) the firm had filed for a drug test "after FDA uncovered serious issues implicating the veracity and reliability of data submitted in support" of the filing. This issue, the agency notes, was raised in correspondence between the firm and the agency in November, and FDA further charged that the December inspection "revealed that four cleared 510(k)s . . . lacked any reliable source documentation." The warning letter states further that the agency finds it likely that the issues raised in connection with the suspended application "would be common to other devices your firm manufactures."

Among the findings that track this issue is one that states that WHPM lacked a design history file for each of four tests, and the warning letter states that the absent supporting data includes "raw data for sensitivity studies; accelerated and real-time stability data and protocols; reproducibility data; and cut-off testing data." Company officials apparently informed the FDA investigator that the 510(k) applications served as the history files and that the raw supporting data had been "thrown out."

FDA also charged that WHPM "uses a notebook to document test line manufacturing for drug of abuse screening tests." While the agency did not specifically quarrel with the content of the notebook in question, the warning letter nonetheless states that such documentation "had not been reviewed and approved by the quality unit for suitability and completeness of information to be captured."

Other citations include those for problematic procedures for corrective and preventive action, device history records, acceptance activities for incoming product, and equipment calibration.

IVD Research warning has a dozen hits

A garden-variety warning letter is bad enough. Worse yet is a warning letter with 12 citations for failure to comply with the quality systems regulations, which is precisely what IVD Research (Carlsbad, California) saw in the agency's Feb. 26 warning letter.

The September-October 2008 inspection disclosed that the company had neither 510(k)s or PMAs for several diagnostics in the firm's "Leptospira" and "Dengue" family of diagnostics. The warning letter also cites IVD for failure to establish a design development plan for five of the Leptospira and Dengue diagnostics, and states that the firm's Nov. 7, 2008, response to the warning letter indicates a willingness to write a "development plan . . . where changes will be required." The agency described this as inadequate in part because it was unclear as to whether the plan referred to new or previous versions of the diagnostics.

According to the letter, IVD's design control procedures did not require a risk analysis or documentation of design validation. The firm's response apparently did not include a copy of new procedures toward these ends, and FDA asserted that "your corrective actions have not been implemented" as of the date of the warning letter.

The company is alleged to have lacked procedures for validation of five diagnostics, and while the firm's November response did include a copy of such a protocol, the agency states that it has "received no information that this validation protocol has been implemented." Cleaning validations were also said to have not been conducted for "equipment used to fill IVD plates." The company's response was initially that such cleaning was based on practices provided by the manufacturer, but FDA held its ground, asserting that the process had to be revalidated in-house.

The warning letter says that IVD had no procedures for determining how many times antigens and antibodies can be frozen and thawed for reuse. The company's response was that lab personnel test antigens and antibodies prior to each use, but the agency stood its ground on the issue, noting that the company had previously promised to undertake such validation studies.

Other citations include those for lack of documentation of calibration for a pH meter "used in production" and two other pieces of equipment, the identities of which were redacted. One of the unidentified items was said to be run with a self-calibration program "that is run with every operation," and the other was said to be sealed in such a way as to make calibration impossible, although the function of this piece of equipment is said to be "verified." The redaction makes it impossible to assign proposed solutions to the findings to these two, but FDA noted that it will verify the corrections upon the subsequent inspection.

Optical surgery equipment maker cited

The March 16 warning letter to American Optisurgical (AO; Lake Forest, California) left the firm with little wiggle room in regulatory terms as FDA stated that the company's response to each of the six inspectional findings cited was inadequate. Add to that the fact that one of the findings was a repeat from an inspection conducted in 2004, and it was a rough day for AO.

FDA states that the company failed to investigate and document a complaint "that resulted in the identification of a software malfunction" and the subsequent revision of the software for an unidentified device. The company's Nov. 14, 2008, letter in response to the inspection was said to have failed to adequately deal with the finding due to lack of documentation about the specific complaint and lack of documentation as to training to prevent recurrences.

Under a citation for failure to verify or validate design changes per procedures, FDA states that AO lacked change orders and documentation of validation of changes to the software for the Horizon phacoemulsification system. The company's response to this citation, said to be the repeat citation from 2004, was deemed insufficient because the firm did not "provide the engineering change order verification document as promised." FDA also cited lack of documentation as to employee retraining on the related procedures as another problem with the response.

The warning letter states that the company's manufacturing and customer service staff had been conducting finished product inspections despite procedures that call for the quality assurance department to handle such work. This was in reference to the firm's Vizual phacoemulsification system, as was a citation for failure to conduct a risk analysis for the device's design.

The company was also cited for failure to notify the agency of a field correction involving the Horizon system's handpiece, used in eye surgery.

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