Basic Planning for Quality

What does the Abbott-FDA Decree mean? What was wrong with the quality of all those tests and why didn't any of the laboratories using those tests notice a problem? Dr. Westgard offers analysis, answers, and a roadmap for the future.

• FDA action against a manufacturer
• A sentinel event calling for independent analytical quality management
• Analytical quality is not a given!
• Responsibility cannot be out-sourced!
• Compliance is not enough!
• Statistical QC can't be eliminated!
• Minimum personnel standards and skills are not sufficient!
• HELP is available from the Internet
• Independent analytical quality management still depends on manufacturers
• References

It's the year 2000 - the start of a new millennium! Everyone is looking forward to the future and to a new and better world. Better quality healthcare is on everyone's list for this new and better world. Better quality laboratory testing should also be on the list!

Just when everyone thought the issue of quality in laboratory testing was dead and buried, a major supplier of diagnostic testing materials and systems was cited for not following the Food and Drug Administration's (FDA) Good Manufacturing Practices (GMP) or Quality System Regulations. This left laboratories scrambling to maintain testing services.

FDA action against a manufacturer

On November 2nd, 1999, the Food and Drug Administration and Abbott Laboratories entered into a legal agreement - a consent decree - to settle a dispute about manufacturing practices. This agreement required Abbott to stop manufacturing certain diagnostic test kits within thirty days (by December 2,1999) and to make corrective changes in the manufacturing processes in it's Lake County IL facilities. On November 19, 1999, the Northern District Court of Illinois extended the deadline until January 10, 2000.

In the FDA "Dear Colleague Letter", the consent decree is described as a permanent injunction that requires Abbott to discontinue sales of certain tests within thirty days because of long standing failure to comply with FDA's Good Manufacturing Practices (GMP) or Quality System Regulation (QSR) and its failure to fulfill commitments to correct deficiencies in its manufacturing operations.

In a press release, Abbott pointed out that the consent decree did not require the recall of any diagnostic products and that certain products would continue to be available.

"The decree allows for the continued manufacture and distribution of medically necessary diagnostic products made in Lake County, Ill., such as assays for hepatitis, retrovirus, cardiovascular disease, cancer, thyroid disorders, fertility, drug monitoring, and congenital and respiratory conditions. However, Abbott is prohibited from manufacturing or distributing certain diagnostic products until Abbott ensure the processes in its Lake County,Ill., diagnostics manufacturing operations conform with the current Quality System Regulation."

The November 3, 1999, Washington Post brought the issue to the public's attention with it's article on "Medical Test Maker Fined $100 Million for Poor Quality Control," in which it stated:

"Abbott Laboratories, the nation's largest maker of medical laboratory tests, agreed yesterday to pay a $100 million fine for failing to correct defects in its manufacturing processes despite six years of warnings. The penalty was the largest ever levied by the Food and Drug Administration."

The LA Times also drew public attention with its article "Abbott Labs to Pay $100m to FDA."

"The issues have to do with manufacturing processes and not with known instances of patient harm,' said FDA medical devices chief Dr. David Feigal. Under the consent decree, Abbott is permitted to continue selling only certain tests the FDA deems medically necessary… The FDA offered an important warning for laboratories, which have certain quality-control to catch glitches with products. Labs that continue to use Abbott diagnostic products should 'increase their vigilance in these areas, to make sure these tests are performing,' Feigal said."

Additional information for the laboratory community was also made available by professional organizations. AACC delivered three MANAGEMENT ALERT bulletins via fax broadcasts in the days following the consent decree and established a webpage with sources of information. In a fax broadcast on November 9, CLMA announced it was petitioning the FDA to extend the notice before discontinuing sales of the tests. The petition would extend the thirty day period by an additional fourteen days. CLMA also established a special page on its website and organized a special audioconference November 18, 1999 to focus on practical strategies for transitioning products affected by the consent decree.

A sentinel event calling for independent analytical quality management

The FDA-Abbott consent decree sounded a warning that laboratories need to independently guarantee the quality of the test results they produce. Virtually all US laboratories have been affected because of Abbott's dominant role in supplying materials and systems for diagnostic testing. These laboratories were faced with the immediate need to validate new methods and provide better quality control of routine testing. For many laboratories, the personnel resources and skills needed to accomplish this are now very scarce due to changes in laboratory management practices and priorities during the last decade.

The need for independent laboratory quality control is fundamental! Many laboratories have become dependent on manufacturers QC instructions and have forgotten the hard-learned lessons of the past:

• Independent QC begins by having control materials that are independent of the calibration materials.
• It is also good practice to have control materials that are made by a different manufacturer than the test system, as confirmed by FDA's recommendation for "the use of quality control materials made by other companies to increase the assurance that these devices are performing successfully".
  
• Laboratories should establish their own means and standard deviations when implementing statistical QC procedures, rather than use bottle values provided by a manufacturer.
  
• Laboratories should select appropriate control rules and numbers of control measurements on the basis of the quality required by the patients and physicians they serve and the imprecision and inaccuracy observed for their methods during routine operation in the laboratory [1].

It's important to recognize that the major problem that needs to be addressed is the poor quality management practices that have evolved in laboratories during the last decade. Laboratories aren't ready or able to exercise an independent responsibility for the quality of their own test results.

The consent decree should be a sentinel event that alerts laboratories to the serious limitations of current quality management practices which often lack independence from the manufacturer. Government agencies should reflect carefully on the state of laboratory quality management and the susceptibility of laboratory testing on a national scale to a problem from a single manufacturer. Accreditation and professional organizations also need to examine their priorities to be sure that the basic requirement for correct test results hasn't been down-played in their efforts to focus laboratory attention on utilization and outcome.

Analytical quality is not a given!

The consent decree clearly exposes the fallacy of the current thinking that "analytical quality is a given." I've been worried about the complacency that has been developing in the 90s - complacency in laboratories, complacency in professional organizations, complacency in regulatory agencies. This issue has been addressed with a discussion of The Myths of Quality, which is the introductory lesson in our course on basic method validation [2]. The situation in many laboratories has deteriorated to the point that educational efforts are needed to re-establish basic quality management practices, which is why we've developed training materials for Basic QC Practices, Basic Method Validation, and Quality Design and Planning. The fundamentals of quality management need to be re-established to support high quality laboratory testing in the new millennium.

Responsibility for quality can't be out-sourced!

In today's busy laboratories, managers and analysts are quite happy when they can find ways to reduce their activities. A common strategy is to bundle quality management activities into contracts when purchasing new analytical systems. For example, when a laboratory buys a new instrument, many managers negotiate to have the manufacturer not only to install the system, but also perform the method validation studies needed to satisfy CLIA validation requirements, provide the QC instructions, control materials, method manual descriptions, and in-service training. Manufacturers provide these services to satisfy the "wants" of their laboratory customers.

In effect, laboratories are out-sourcing many quality management activities by purchasing complete systems from a manufacturer. That practice is clearly dangerous. The responsibility for the quality of the test results can never be out-sourced, even if some of the activities are performed by others. Quality can be guaranteed only when the laboratory accepts it's responsibility and properly manages its own testing processes!

Compliance is not enough!

"Compliance" has become the management focus as we enter this new millennium. Professional organizations tout compliance training programs. Scientific meetings feature compliance workshops. Laboratories are required to develop compliance policies and programs and may even have compliance officers. Avoiding fraud and staying out of jail are getting more management time and attention than quality. Does anyone think this inspires the laboratory staff to maintain and improve quality?

Compliance management got its start from CLIA. It wasn't mandated by the CLIA regulations, but compliance became the main response to the regulations. It is evident that management regards the minimums stated in regulations as all that need to be done, therefore these minimums have become maximums in laboratory practice. For example, because the regulations say it's necessary to run two controls, then bottom-line managers never run more than two. Some people seem to accept that the government has become very smart in the area of quality control, even though they don't think the government has a clue about anything else.

The CLIA rules might actually provide good guidance for quality management if the regulations were ever completely implemented. It would be nice to have the "final-final" CLIA document published. It would be even better if the FDA were to implement the process for clearance of a manufacturer's QC instructions, as called for in the original regulations. The continual postponement of these regulations for validation of manufacturers' QC is a serious problem and compromises the overall effectiveness of CLIA.

Statistical QC can't be eliminated!

Statistical QC has been a fundamental quality management technique in industry since the 1930s and in laboratories since the 1960s because it provides an independent way of monitoring the quality of a production process. In spite of this, there have been efforts to do away with statistical QC for laboratory testing. These efforts have been initially pushed by industry to expand point-of-care markets, even though statistical QC still provides the most efficient technique for monitoring the many steps in a testing process, as well as providing a quantitative measure of operator proficiency [3]. Expanded quality management systems should be built on statistical QC, rather than attempting to eliminate statistical QC.

Minimum personnel standards and skills are not sufficient!

CLIA's minimum requirements for personnel have now been achieved in many laboratories. Again, because of the compliance mentality, the net result has been a lower level of the education for laboratory analysts, a serious reduction in training programs for clinical laboratory scientists, and, of course, some reduction in personnel costs, which justifies everything for bottom-line managers.

Even some laboratory professionals have capitulated to this trend of "dumbing down" laboratory medicine. One paper published in 1997 [4] concluded that "QC is costly, and laboratorians frequently do not follow established QC practices, in part, because they are complex. To improve compliance, we believe QC practices must be simplified." In short, if the job is too complex for lower skilled people, the solution is to simplify the job. (Let's keep this little secret to ourselves -- I don't want my plumber taking over for my surgeon!)

HELP is available from the Internet

Laboratories that want to upgrade their skills in analytical quality management can take advantage of Internet training materials. Our course in Basic Method Validation provides a good starting point for understanding analytical performance. Our course in Basic QC Practices provides the fundamentals of statistical QC for laboratory application. This course in Basic Quality Planning builds on these fundamentals and addresses the management issues of what quality is needed and how to assure that quality is achieved in routine operation. Important elements of this course include:

• The why of quality planning. A review of principles of Total Quality Management and existing regulatory, accreditation, and practice guidelines provide the background for understanding why quality planning is an essential part of laboratory quality management.
  
• The what of quality planning. A step-by-step process provides a quantitative way for setting method performance specifications and selecting control rules and numbers of control measurements on the basis of the quality required for a test and the imprecision and inaccuracy observed for a method.
  
• The how of quality planning. Quality-planning tools, such as the chart of operating specifications, provide an easy way to perform quality planning.
  
• The when of quality planning. Anytime, with the quick and effective quality-planning process and tools provided here.
  
• The who of quality planning. That's you! You have a professional responsibility for the quality of your work. Our objective is to help you do your job better and manage quality in an appropriate way.

Independent analytical quality management still depends on manufacturers

Laboratories are dependent on manufacturers to provide the test systems needed in today's laboratories. There is a shared responsibility to deliver the test results that are needed for patient care. An important part of the laboratory's responsibility is to assure the quality of the final test results before they are released and reported. Manufacturers can help the laboratory carry out it's responsibility by supplying QC materials and decision-support software that will allow the laboratory to easily implement and efficiently operate the appropriate QC procedures. However, the laboratory is still responsible to select and implement testing processes and QC procedures that will assure the quality needed for the patients it serves.

REFERENCES

1. NCCLS C24-A2. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline - Second Edition. National Committee for Clinical Laboratory Standards, Wayne PA, February 1999.
2. Westgard JO. Myths of Quality. Lesson 1 in Basic Method Validation. Westgard QC, Madison, WI 1999, pp. 3-8.
3. Westgard JO. Taking care of point-of-care QC. Clin Lab News, August 1997.
4. Howanitz PJ, Tetrault GA, Steindel SJ. Clinical laboratory quality control: a costly process now out of control. Clin Chim Acta 1997;260:163-174.