A Diagnostics & Imaging Week

The Centers for Medicare & Medicaid Services reported recently that it will cover the use of positron-emission tomography (PET) in the initial staging of most solid tumors. Previous coverage for such uses of PET fell under the coverage with evidence development (CED) rubric, which requires that reimbursement be tied to the conduct of a clinical trial designed to establish whether such treatment is reasonable and necessary.

CMS reopened the question to a national coverage analysis in January, but the coverage decision deals primarily with the initial use of PET to diagnose and stage the treatment of most of the cancers in question, a list that includes lymphomas and melanomas and cancers of the cervix, breast and ovary. However, CMS's decision also provides reimbursement for follow-up imaging for diagnoses of myeloma and for cervical and ovarian cancers.

Acting CMS administrator Charlene Frizzera said in the statement that the decision "shows that the CED program is a success," although the statement also notes that the decision "is the first time that CMS has reconsidered a coverage policy based on new evidence developed under the CED program."

The agency opted in 2005 to put PET on the CED list contingent on the submission of data to the National Oncological PET Registry (NOPR), operated jointly by the American College of Radiology (ACR; Reston, Virginia) and the ACR Imaging Network (ACRIN; Philadelphia). Among the other participants in the ACRIN effort are the Society for Nuclear Medicine (SNM; Reston, Virginia) and the American Society for Clinical Oncology (Alexandria, Virginia).

James Thrall, MD, chairman of the board at ACR, said in an April 6 statement that the NOPR "is a shining example of how the medical community can interact with government on research that can ultimately save and extend patients' lives." In an April 3 statement, Robert Atcher, PhD, President of SNM, described the move as "a major victory for patients" and said the coverage "demonstrates the intrinsic medical value of PET and the important role of these scans in diagnosing, staging, restaging and monitoring treatment for many cancers."

Firm's supporting data for 510(k)s said lacking

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 warning 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 states 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.

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