Ethchlorvynol

Learn how a lab supervisor in a Midwestern toxicology lab set the wheels of reengineering in motion to manage a dramatic increase in workload from approximately 400 to 1,300 confirmation samples per month.

About two years ago, the workload in our toxicology laboratory, which performs clinical trial studies for pharmaceutical companies, tripled within a 3-month period. As a result of this dramatic shift in test volume, many of our employees were working almost double shifts daily, which was beginning to fire up some serious employee burnout.

As supervisor of our section at the time, the onus was on me to manage this heavy volume of work while maintaining the quality needed to meet our regulatory requirements. I knew that to provide the services our customers had come to expect, we needed the ability to validate new methods quickly and adapt to frequently changing volumes. It also was imperative that our lab be ready - with little to no advance warning - for client inspections. And on top of all this, I had to keep my . . . where to begin!?

My request for two additional employees was granted right away, but I still had to find eligible candidates and train them, which would take months. In the meantime, I had to develop strategies for managing the additional work and be able to implement these ideas as my laboratorians continued to work 10- to 14-hour days.

For some immediate relief, my first course of action was to eliminate unnecessary procedures, which, in turn, led to the need to rethink established methodologies. We also began to look into automation opportunities and the use of personal computers. Unlike older sections in our laboratory, toxicology (low man on the totem pole) was not yet on the computer network, which meant our people had to input all computer data manually. This also meant we had to be more innovative with procedures we could control ourselves.

Following is a step-by-step account of how we reengineered our lab section to keep pace with current test volumes, customer demands, regulatory pressures, as well as our own expectations of ourselves.

Trading tubes

Our first step in the reengineering process focused on finding a new specimen tube. Upon receipt of a urine specimen in our toxicology section, the patient ID barcode label was read and a test request label generated. This specimen was received in two 15-mL tubes, so we had to match up the two tubes and generate two labels for each accession number. My senior technologist and I found an acceptable 30-mL tube that eliminated the duplication of work, and following discussion with all involved departments, this larger tube was implemented for all future projects.

Since one tube costs less than two, and because our new tube does not require a sleeve to protect against leakage, our company is saving money. Further, technologists no longer have to line up two tubes in our racks, so there is less chance of testing errors. And our employees save time by not having to go through hundreds of specimens matching pairs of accession numbers.

Worksheet redesign

Step 2 involved redesigning worksheets for our immunoassay screens and thin-layer screening chromatography (TLC) tests. In the past, our department was spending an extraordinary amount of time preparing screening worksheets to begin the day's work. Our laboratorians were writing accession numbers on these worksheets manually, which was time consuming and prone to interpretation errors. We decided to generate additional labels when specimen tubes are first received and to use these labels on our worksheets.

Before we could implement this change, however, two minor problems had to be resolved. First, our lab assistant was scanning a tube five times to generate five labels (for tubes and various worksheets). Our programming department modified this procedure so we could print as many labels as we needed by scanning the tube only once. Our second obstacle: Our new labels didn't fit the worksheets, and our original worksheets had been designed on the company's computer, making them difficult to modify. Fortunately, our gas chromatography mass spectrometry (GC/MS) systems contain Microsoft Excel software. After some self-training in Excel at home, I was able to revamp our worksheets to suit our needs (see worksheet, p. 38).

Screening process revisited

With initial startup under control, it was time to look at our test screening process. Most of our projects require immunoassay screens and simultaneous TLC testing, along with manual spot tests for ethchlorvynol, acetaminophen, and salicylates. After reviewing our entire project list for accuracy, we found TLC testing unnecessary for many projects. Eliminating these assays saved tech time as well as reagent costs.

Manual spot tests are not only time consuming but apt to cause interpretation problems, so we decided to investigate opportunities to automate these particular assays. One manufacturer helped us to adapt its acetaminophen assay to our immunoassay instrument. Since we were already running these same samples on our TLC, we chose this system as our alternate physical methodology for confirmation. We then adapted two commercial salicylates methodologies to our immunoassay instruments: one for immunoassay screening and one to verify positive salicylates. Now one technologist can handle both immunoassay screens and manual ethchlorvynol spot tests.

Streamlining quality

Quality control and quality assurance (QC/QA) issues were next on our list. We considered whether conducting our own unscheduled equipment maintenance was a duplication of effort, and if this maintenance could be performed solely by our contracted service rep. We then scrutinized the effectiveness of our QC program. Again Excel helped us to prepare easy-to-use QC sheets and maintenance logs. From here, we were able to schedule service and avoid downtime due to unscheduled maintenance. We also could redefine our QC program and monitor it more closely to prevent excessive failed runs.

Confirmation testing

Reengineering confirmation testing proved to be a formidable task because our samples contain multiple drags at high concentrations requiring dilutions, which further increase the workload. Our promise to customers is to report negative drug screens by 6 pm on the day of receipt and to confirm and report all positives by 6 pm the day following receipt. With only one commercial high performance liquid chromatography (HPLC) system and two GC/MS systems in house, there was no way we could meet our turnaround times for so many projects. We [TABULAR DATA OMITTED] promptly ordered a third GC/MS. Still, we knew it would take several weeks to receive and validate this new instrumentation. Changes had to be made now!

Again, we approached this challenge determined to eliminate duplicate work. For instance, phenothiazines detected by TLC screening were being confirmed by GC/MS - a long and tedious process. After determining GC/MS detection limits for the numerous phenothiazines, we found HPLC to be the better confirmation method, so these samples were moved to that instrument. Additionally, opiates found positive by immunoassay screening were confirmed by GC/MS on both a hydrolyzed, derivatized sample and a non-hydrolyzed, non-derivatized sample. After checking GC/MS detection limits, we found the HPLC instrument just as suitable for our non-hydrolyzed samples, which were moved to the HPLC, too. This change reduced the enormous amount of time spent daily on GC/MS data analysis and certification and freed up these two instruments for other confirmations.

We then looked at the assays that make up the bulk of our confirmation workload: alkaline and acid scans by GC/MS. Acid scans were being injected on the GC/MS using the same acquisition method used for the alkalines. Yet after making a list of all the drags and their respective retention times, we found that by setting up a different method for acids in which only the stop time was modified, the run time for these tests could be reduced from 23 minutes to 13 minutes.

Similar results were achieved with the alkaline drags. Most of them had retention times of less than 13 minutes, and only a few actually needed to run for 23 minutes, yet we were running everything at 23 minutes. I set up another data acquisition method with a run time of 14 minutes, which almost doubled our GC/MS capability.

Two problematic assays were improved with minor changes. The GC/MS assay for benzoylecgonine frequently had to be repeated because of a large contaminant that co-eluted with the benzoylecgonine. After validating this method with a different derivatizing agent, we were rewarded with clean chromatograms and an assay that worked every time. Our cannabinoids assay had a higher-than-expected rate of failed runs, typically due to a contaminant peak that caused our negative control to read high. This problem was eliminated by choosing a different quantitating ion.

After these changes, we reviewed quality issues for these assays. We used an in-house control for alkalines and acids. Considering the regulatory issues involved, documentation required, and staff time necessary to prepare and verify this control, we found it less expensive to buy a commercial control that contained five barbiturates at 25% above the cutoff level. (Our in-house control contained only butalbital and secobarbital.) Our logs for recording controls were too simple, excluding the compounds and their retention times. This made it difficult to train new technologists and troubleshoot. The spread sheet came to the rescue again by helping to refine maintenance logs and prepare new control sheets.

Data analysis

Two or three technologists were needed each day to perform GC/MS data analysis for six assays: alkaline and acid scans, opiates, benzoylecgonine, benzodiazepines, and cannabinoids. While data analysis for benzoylecgonine and opiate assays was fairly quick (we were looking for only a few compounds), the list of compounds in the alkaline, acid, and benzodiazepines assays was quite extensive. It has been our policy to check each peak against our library, and if we are unable to find a particular compound, we extract a minimum of the three largest ions for each suspected compound and print them out in individual and overlapped form. This procedure is extremely tedious for technologists and frustrating for me. At the end of the day, pressed for time to certify and file results, I would frequently find the wrong ions extracted or the correct ions at the wrong retention time.

Fortunately, our company again was willing to invest the money necessary to improve a bad situation. I worked for two days with a GC/MS representative devising customized macros to extract and print these ions. If no ions for the expected compound are present, an empty window prints at the expected retention time. Within days, I was able to go back to our lab and implement these macros for all assays excluding a few alkaline compounds. Data analysis time has been dramatically decreased, and our internal result review is now much quicker.

Automation startup

The last area in our section that required reengineering was automation. When our toxicology section was initially implemented, two automated extraction systems were purchased. But due to testing volumes. inadequate staffing, and lack of knowledge, these systems were not yet up and running. Again, we invited the vendor to come in for two days to provide us with basic training. We soon understood how to operate the system but we still weren't sure where to begin and which assays to use.

Making a list of all the compounds on our test menu, we were surprised to learn we had almost 200 of them. To validate our instruments, we have to prove we can detect the same compound levels as those detected by manual methods. To accomplish this, we prepared and extracted standards and controls at the detection limits of the manual methods. We also ran correlations with patient samples extracted by manual methodologies. Our extraction system was validated for benzodiazepines first. Acidic drugs were next on the list, followed by alkaline drugs, opiates, and benzoylecgonine.

Our automation changes have resulted in numerous benefits for our lab section. For starters, employees are now safer since they are exposed to chemicals only when refilling reagents (usually once a week). Additionally, the smaller reagent volumes used by automated analyzers (1.5 mL versus 5 mL for manual methods) saves us on reagent costs and prevents test order cancellations due to insufficient sample volumes. Automation also saves us from having to purchase an additional hood, which is necessary for manual extractions. Finally, using automated equipment has resulted in a five-fold decrease in the amount of hazardous waste generated.

A powerful tool

We're proud that we've been able to deal with rapid change in our section and to make improvements to meet our customers' needs. The data we've collected as a result of our reengineerlng initiative also have enhanced our quality and productivity, as well as made the training of new staff much easier. All these improvements were realized, without needing to hire additional FTEs, through basic process analysis.

Our technologists are delighted with the progress we've made in our area over the past two years. No doubt, we're now all firm believers in the power of reengineering.

Saundra Gail Kaiser, toxicology supervisor for Covance Central Laboratory Services in Indianapolis, Ind., at the time of this writing, currently is manager for the same department.

COPYRIGHT 1997 Nelson Publishing
COPYRIGHT 2004 Gale Group