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Q is for Quality

Despite the vigilance of federal, state and local regulators and of accreditation organizations that evaluate and certify laboratories, the development and maintenance of quality in laboratories are constant concerns.

by Bernard B. Tulsi
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Despite Good Science and the Best People, Labs Will Suffer Without More Attention Paid to Quality

In the laboratory context, quality is a measure reflecting how effectively laboratory management and staff are able to deploy their instrumentation, tools, reagents and software to conduct laboratory tests and investigations with validated methods and regulated procedures to produce accurate and consistent results on a routine basis.

The majority of laboratories are organized along inhouse models—within companies, government agencies and universities—or as service entities that provide an array of analytical testing for a variety of customers. Irrespective of the end user of the output generated by laboratories, “Good quality translates into greater demand for services. Bad quality carries the risk of losing customers, and in a competitive environment, laboratories cannot afford to lose good customers,” says Dr. Henry Nowicki, president of PACS Testing, Consulting, Training, which offers a number of training courses in chromatography, mass spectroscopy and related areas for laboratory personnel.

Despite the vigilance of federal, state and local regulators and of accreditation organizations that evaluate and certify laboratories, the development and maintenance of quality in laboratories are constant concerns. Because much can and does go wrong and quality can be undermined by a variety of variables, laboratories may find it necessary to commission audits aimed at ascertaining the quality of their operations.

Laboratory audits and inspections are listed among the capabilities of Nowicki’s group. “Before inspecting and auditing a lab, it is important to get a solid understanding of its equipment and the standard operating procedures, preferably of its most widely used tests. This is essential to get a good sense of a lab’s activities and processes and an understanding of the measurements it uses.

“Furthermore, it is important to know whether the lab uses state-of-the-art equipment and to have a good grasp of the staff ’s levels of training and experience. In highly specialized labs, which are common today, it is important to determine whether they have the right equipment, training, data collection, and recording and archiving, among other key attributes,” says Nowicki.

If and when deficiencies are found, the next step for laboratory auditors is usually to make recommendations to management about corrective action. Some adjustments may be necessary to ensure that labs are compliant, and that they are able to stay out of regulatory trouble and avoid the enormous costs associated with it. In some cases strategic changes may help them to streamline their processes and improve productivity.

Nowicki says that once an audit is completed and evaluated, it is important to bring anything amiss to the attention of the lab managers. It is also vital to inform them about potential remedies and to show them how to implement changes capable of fixing deficiencies in the operation as well as delivering key benefits. “It helps to show them the marginal returns for taking the recommended action. Lab managers really take note when they realize that they may be deficient compared to other labs and that changes are essential to stay competitive.” In fact, paying close attention to quality and validated methods and data has been credited with helping laboratories to retain their competitive edge, he says.

“In fact, insufficient attention to quality, validation and inadequacies in proper management oversight has been known to lead to the demise of laboratory-related business enterprises,” says Dr. Shib Mookherjea, who is currently senior manager for analytical services at Allergan, Inc. (Santa Barbara, Calif.), and whose lab quality experience has been honed in a number of large pharmaceutical companies and as an instructor on quality issues with the American Chemical Society and other professional organizations.

“We have to build and maintain quality and validation from the very outset; otherwise our measurement processes and our data will become questionable. People are realizing more now that they have to do increased due diligence and can’t go on taking shortcuts, an approach that has created big problems for labs in the past.”

He says that while there are still some laggards, more lab managers are inculcating in their staff the idea that regulations set out by agencies such as the FDA or the EPA are binding requirements, not merely suggestions. Sometimes that connection is missing in labs, and it would serve these organizations well if top management were to take repeated measures to instill the understanding that regulatory requirements have serious meanings.

Mookherjea says that quality practices vary by industry and by setting within industries and organizations. What cuts across several situations, however, is quality management system infrastructure, which may either be part of a regulatory regimen or optional. He says that some companies, especially in the pharmaceutical sector, are required to conform to regulatory guidelines such as good laboratory practice (GLP) and good manufacturing practice (GMP), often without exception.

“The infrastructure of the quality system is very important in maintaining GLP, GMP or ISO 9000 focus. With GLP, elements have to be defined at the outset because GLP is a very structured environment. For instance, it is not sufficient to say that there is document control, which is a GMP task, in the case of GLP. There has to be an archivist for GLP final reports, which is not required in GMP.”

Mookherjea points out that in a number of companies there are questions about where GMP starts and GLP ends. He says management needs to be aware of this and to understand clearly the purpose of GMP and the tenets of GLP.

“This is essential in a regulated environment, but even in nonbinding situations there is a need to maintain an infrastructure of the quality system—and that is where quality control (QC) becomes very important.”

He says that QC is more or less the general lab procedure that is needed to maintain the focus on data quality. “It is basically concerned with how to calibrate instruments and how to maintain the documentation associated with sample management systems and other procedures,” Mookherjea says.

By contrast, quality assurance (QA) is more strategic. “Imagine QC as a small circle and QA as a slightly larger one, because QA gets into the development of infrastructure and how to maintain the quality control focus, and it may include auditing, documentation and training. What the two different circles portray is that QC is limited to day-to-day operations, while QA is more open and strategic,” says Mookherjea.

Turning to the question of method validation, Mookherjea says that in every process, on a risk assessment basis, management has to make a decision on whether the process needs to be qualified or validated. He says, “If a lab is involved in developing a manufacturing process, then that must certainly be validated. If it is involved in a cleaning process, then the cleaning validation will take effect, or if it is a case of an aseptic method, then aseptic validation comes into play.”

When dealing with methods, it is important to understand the goals of the methods, according to Mookherjea. “To do that, you need to go into the design stages of the method and assess what is needed to achieve the goal. Does the method require LC or LCMS or GC or AAICP? That depends on what parameters must be validated, what kind of resolution is needed and what level of laboratory quality assurance is required, among other factors.”

Mookherjea says that method validation is only one of the components of QA. Another key component is traceability based on unique identification numbers for samples. “There are several cases of samples getting mixed up and misplaced because people do not take the time to develop distinct alphanumeric labels for them. They do not take the time to understand how an analytical work request is created, what the goals are, and whether it is specific enough to convey what is being requested by internal users or external customers.”

Turning to the issues of management and leadership, Mookherjea says that all quality standards recognize that one of the most essential factors in the implementation and enforcement of quality in any setting is management. Invoking quality gurus such as William Edwards Deming and Joseph Moses Durant, Mookherjea says quality is everybody’s responsibility, “but quality needs to start at the top, and management has to buy into quality first; then it has to be carried through the entire organization.”

He says that quality is not static but rather a continuous improvement process. “Quality is not a project, it is a continuous process, and both Deming and Durant have maintained that quality must be a never-ending commitment of a company.”

In describing the drivers of quality in the laboratory environment, Mookherjea says that there are three large buckets: one contains the fundamental science, which comes first and drives everything; the second contains the technology, software and information systems; and the third contains management techniques and roles and “the big letter Q for quality. If attention is not paid to the quality side, despite good science and the best people, the entire structure can collapse.”

Prior to considering quality, it is important to know the science behind it. “If people do not understand the underlying analytical chemistry of an analytical process, for example, they will of necessity use a robotic rather than a scientific approach in their laboratory analyses.”

As a result, welltrained personnel are another vital component of a well-functioning laboratory, according to both Mookherjea and Nowicki. “Training should be ongoing to keep up with rapidly changing technology and new regulations. Human resources are crucial, and management has to select and empower them and provide the resources for them to thrive in an environment of scientific discipline and professionalism’’, says Nowicki.

“Overall, there could be more training of personnel—training that includes the use of computerized systems and data interpretation—to produce a higherquality staff for laboratories. A lot of the training that chemists receive lacks exposure to key instrumentation, and a number of academic universities do not teach fundamental skills such as how to interpret mass spectrometry data, which should be a core skill. Motivation is very important in the lab environment, and training helps tremendously in that process,” says Nowicki.

Both experts acknowledge that new analytical technologies have been a huge help in maintaining laboratory quality. Mookherjea points to HPLC equipment, particularly the introduction of the autosampler, which he describes as a quantum leap in analytical instrumentation that provides laboratories with a tremendous advantage.

Despite some major gains, however, Nowicki points to the need for technology to make laboratory measurements faster and to deliver results in minutes instead of hours. “We need to push to have technology that can do analyses faster, better and cheaper. Instrument developers need to come up with new measurement technologies based on DNA and other techniques. They are doing that, but this is a continuous process, and there is still more ground to cover.”

To be sure, some major causes for concern still exist. Mookherjea says that in the past few years, “Quality has improved by leaps and bounds, but it is still not where it should be. The focus is not there because companies are changing rapidly and dynamically.

“There is a lack of constant awareness by top management teams that build labs and focus on the building rather than on the far more valuable and essential human resources. They do not promote ongoing training but instead rely on the skill sets that workers are recruited with. They need to find ways to expand on those skills. Lab workers need to be trained on regulations and new technologies— that is where a big gap exists.”

Despite strong optimism about the future of analytical laboratories, Nowicki was more emphatic about some of the current shortcomings. “I think that laboratory leadership has largely failed. Management has cut the head count in labs to such an extent that the remaining personnel are overworked—and when people are overworked and worn out, quality suffers.”

The other side of the problem is that when leaders try to run their operations with too many workers, cost-effectiveness suffers, he says. “There must be a careful balance between the number of people needed and the quality of the output,” he says.

In addition, the quality should match the business. “Some areas must have high, precision quality all the time, while some others may be able to operate at a lower quality threshold. In every laboratory, the key question that must be addressed at all times is, ‘What level of quality is required?’”

Still, Nowicki is confident that labs will deliver on the desired quality goals. “Laboratories know their problems, and they know their strengths and weaknesses.… I am encouraged that over time laboratories will get better.”