CEO SUMMARY: On March 13, 2007, the Food and Drug Administration sent a warning letter to Abbott Laboratories’ Chairman and CEO, Miles D. White. The letter identified nine quality system violations and requested a satisfactory response by August 15, 2007. The warning letter is based on deficiencies identified by FDA inspectors at Abbott’s manufacturing facility in Irving, Texas, during the period October 30 to November 17, 2006.
IN THE DELICATE DANCE between regulators and the companies they regulate, the clinical laboratory industry has become aware of new issues unfolding between the United States Food and Drug Administration (FDA) and the diagnostics unit of Abbott Laboratories, Inc. of Abbott Park, Illinois.
Last month, the FDA posted a letter, dated March 13, 2007, on its Web site. Addressed to Abbott’s Chairman and CEO, Miles D. White, the letter requests specific responses to deficiencies identified during inspections it conducted of Abbott’s Irving, Texas, manufacturing plant. These inspections took place between October 30, 2006, and November 17, 2006. (The warning letter can be found at https://www.darkintelligencegroup.com/the-dark-report/laboratory-compliance/fda-sends-warning-letter-to-abbott-laboratories/.)
Abbott manufactures and assembles several different models of chemistry instru- ments and immunoassay analyzers at its facility in Irving. The March 13 warning letter was issued after a series of letters and meetings between officials from the FDA and executives of Abbott Laboratories in recent months. In the letter, the FDA lists nine quality system violations.
The Chicago Tribune and news outlets including Reuters and AP reported on the FDA warning letter. Wall Street seems to be taking a “wait and see” stance. Brian McKaig, an official at General Electric Healthcare, which is about to acquire most of the diagnostics business of Abbott Laboratories, told reporters that GE continues to believe the acquisition will be completed before mid-year. McKaig also noted that “this is Abbott’s issue to resolve and GE Healthcare is being kept informed.”
News of this most recent FDA warning letter has come to the attention of a growing number of lab directors and pathologists. It reminds them of Abbott’s earlier issues with the FDA. In 2000, as a result of quality system deficiencies in the manufacture of reagents and test kits, the FDA took the extreme step of directing Abbott Laboratories to cease selling more than 120 different assays.
Withdrawal of these products from the market caused consternation across the laboratory industry. Individual labs scrambled to find alternatives for those Abbott assays they used in their labs, but which were now no longer available. Not until 2003 was Abbott able to satisfy the FDA and restart the sales of many of these assays. That is why, having lived through this experience once before, some laboratory managers say they will closely watch how the diagnostics division of Abbott responds to the FDA’s warning letter.
In a public statement, Abbot Laboratories acknowledged that it was working with the FDA. “We take questions about our quality processes very seriously,” stated Kelly A. Morrison, Director, External Communications and Corporate Public Affairs. “Abbott has already taken a number of steps to address the issues outlined in the letter since the initial general inspection, and has communicated those specific actions to the FDA in writing. We are in the process of responding to the FDA with an updated action plan to address their outstanding concerns as quickly as possible.”
In its March 13 letter, the FDA stated “the Agency is not satisfied with the pace and the results of your firm’s past corrective actions as they have not been effectively, timely, and globally implemented for your entire family of analyzers.” The FDA requests that Abbott engage outside experts to evaluate the situation. It also asks Abbott to respond, by August 15, 2007, with evidence that the issues have been resolved.
FDA Requests Action
The FDA noted that it is “not satisfied” with Abbott’s progress on resolving the current issues. It then stated that “failure to promptly correct these violations may result in regulatory action being initiated.” Actions available to the FDA include seizure, legal injunction, or civil penalties.
Based on its inspections of the Irving facility’s manufacturing and assembly processes for automated chemistry and immunoassay analyzers, the FDA also declared that, per federal law, these instrument systems were “adulterated…in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformance with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. Your devices are also misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), because your firm submitted several late MDR reports.”
The FDA’s letter describes nine specific “quality system violations.” These center around inadequate actions taken at the Irving facility to correct quality and performance issues affecting the instrument systems manufactured or assembled there.
“DOA” Analyzer Reporting
In quality system violation #2, the FDA letter states, “Your firm’s management failed to review all quality sources and take appropriate corrective actions to address various quality issues or document their adequate justification for not taking corrective actions. For example, your Dallas ADD’s site management used a ‘dollar value’ as the alert level for part replacements as a measure of malfunctions of the analyzers upon installation at their user sites to determine whether or not to further evaluate, conduct investigations, or take actions to address potential quality issues with your analyzers. If the cost of the replacement parts or ‘bad installs’ did not exceed a ‘dollar’ alert level, there was no investigation conducted. See your firm’s Quality Metrics Report ‘The Installation and Performance Metrics for the c8000, i2000, i2000SR analyzers’ that characterized that a number of the analyzers were found DOA (dead on arrival) upon installation in each month from 10/2004 through 9/2006.”
One conclusion that can be made from reading the nine quality system violations is that the FDA was concerned that Abbott was aware that specific components of these instruments did not meet specifications, yet, over the 24 months that preceded the FDA’s 2006 inspection, Abbott had not taken successful actions to correct this situation.
At this point, the FDA’s March 13 letter puts Abbott Laboratories on notice that its Irving, Texas, facility has failed to meet quality system standards. The letter asks Abbott to do two things. First, the company is requested to provide information about the corrective actions it will take to address the deficiencies in performance to its quality system guidelines.
Second, the FDA asked Abbott Laboratories to submit “certification by an outside expert consultant that he/she has conducted an audit of your establishment’s manufacturing and quality assurance systems relative to the requirements of the device’s QS regulation (21 C.F.R Part 820) and the MDR regulations (21 C.F.R. Part 803). Deadline for submitting certification to the FDA of the outside audit is August 15, 2007.”
Watching FDA’s Next Move
To date, financial analysts have shown little concern over this matter with the FDA. Wall Street investors continue to support the current share price of Abbott Laboratories. Meanwhile, General Electric continues to move forward with its acquisition of Abbott’s diagnostics business. Similarly, when laboratory managers and pathologists first learn about the FDA’s March 13 warning letter, there is more curiosity about this issue than concern.
Abbott Tracked “Arrive Alive” & “DOA” Instruments At Time of Installation in Customers’ Laboratories
THERE’S A GENERAL ASSUMPTION in the laboratory industry. It is understood that, when a laboratory customer pays several hundred thousand dollars for a brand-new analyzer, that analyzer should arrive at the lab, be uncrated, and operate properly from the start, after the normal tweaks and attention necessary to bring it up into full operation.
Abbott Laboratories was measuring its success or failure at delivery and installation in its customer’s laboratories by using monitors it called “DOA”, for “dead on arrival” and “Arrive Alive.” In its March 13 warning letter to Abbott, the Food and Drug Administration (FDA) called attention to this situation in item six under the section titled “Quality System Failures.”
The FDA wrote about the “failure to establish and maintain adequate procedure for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria prior to releasing the devices for distribution, as required by 21 C.F.R. §820-80(d). Your factory testing failed to adequately detect and reject defective device components, including the pressure monitors and pumps, and nonconforming device functions prior to releasing the analyzers for site installation. According to your firm’s DD005 Metrics Report for the period of November 2004 through October 2006, many analyzers were characterized as ‘bad installs’ at the user sites and their components had to be replaced. For example, this report stated that in April 2005, out of the [redacted] installations of the i2000SR analyzers, [redacted] analyzers were ‘Dead On Arrival’ and that the ‘Arrive Alive’ percentage was 76%.”
Although the FDA redacted the actual number of analyzers installed in the month of April 2005 in the public release of the May 13 letter, it did leave the reference to the fact that 76% of the delivered analyzers “arrived alive.” Therefore, during this particular month, one in four analyzers that Abbott delivered to customer laboratories failed to function at install on site, according to the company’s quality and performance specifications.