Disposables in the Quality Control Laboratory

BioPharm International, BioPharm International-11-02-2006, Volume 2006 Supplement, Issue 6

The deliberate reuse of disposables has caused many clinically significant problems.

Despite their rapid adoption and major contribution to the reduction of operating costs, disposables are misunderstood by many. By their very nature, disposables must be manufactured in a manner that minimizes costs. In theory, at least, disposables should not cost any more than it would to use the corresponding reusable item one time.

This is where the advantages of disposables lie. However, the cost of using an item once cannot be estimated simply by dividing it by the number of expected uses. The cost of recycling, which usually involves cleaning and storing, also must be considered. The requirements for a cleaning validation, storage space and facilities for this recycling will often add a significant cost.

When disposables were introduced to the quality control laboratory, one of the first areas of savings was in cleaning costs. Previously, many large laboratories had full-time dishwashers who worked in a central facility or circulated among specialty laboratories. In organizations too small to gain the efficiency of a dedicated worker, cleaning consumed considerable amounts of employee time; even when the job was assigned to the most junior analyst, the cost of the work, including periodic breakage, was significant.

With some measuring devices, a major cost arose from wear and tear that required periodic recalibration or maintenance activities. Pipettes and syringes wear out through slow chemical corrosion or the mechanical abrasion of surfaces. It is necessary to validate the cleaning procedure and prove that the calibrations are maintained when the items are reused.

False Economy

The need for recalibration or proper maintenance often caused difficulties for people who attempted to reuse disposables. Many laboratories found disposables attractive because of their relatively low initial cost, and then, in a misguided attempt to extend their savings, they tried to reuse items that were really designed for a single use.

In one laboratory, disposable plastic cuvettes were routinely reused by rinsing them with deionized water, followed by an ethanol rinse to help them dry rapidly. The ethanol leached material from the plastic and eventually caused a change in the surface properties of the cuvettes. The result was that the chromophore was adsorbed on the cuvette surface, and then removed during the rinse. The bound chromophore did not have the same absorbance maximum as the chromophore in solution. The net effect was to change the limit of detection for the assay.

The actual effect was to displace the standard curve to the right, along the concentration axis, so that the zero absorbance reading actually occurred at a concentration that was a significant quantity. In this laboratory, the problem was compounded because a standard curve was not used, but the chromophore's extinction coefficient was used to calculate its concentration from a single point reading. A related problem would have arisen if they had run a standard curve, and instructed the software to force the line through zero, as is done in many laboratories.

It is easy to understand why a laboratory trying to save money by reusing disposable cuvettes would also use a single-point assay without a standard curve. In this situation, the problem did not come to light until the changed limit of detection was found during a revalidation of the assay. The revalidation occurred only after an FDA investigator "suggested" that a four-year old assay might be due for a revalidation. As might be expected, the company was trying to save money by minimizing revalidations.

While this may seem to be a minor event, the deliberate reuse of disposables has caused many clinically significant problems. These have ranged from missionary hospitals reusing syringes and needles and contributing to an outbreak of Ebola virus, to US hospitals reusing venous catheters and introducing pyrogens into unsuspecting patients.

Environmental Issues

Environmental issues come in two forms. First there are the problems that arise from the sheer quantity of the material that is being discarded. The use of inexpensive glass items such as pipettes and flint glass test tubes produces material that is easy to recycle and is relatively inert even if not recycled. Also, the production of glass is not really depleting the world of critical material.

Some plastics are very stable and in this respect they resemble glass; the primary problem they create is one of volume in landfills. Most plastics are made from petroleum, but the amount of petroleum consumed for making plastics is relatively small compared with the amount consumed as fuel.

Other problems exist with some plastics that are used for many disposables. Sometimes, the inert plastics themselves are not as bad as the plasticizers and additives that are inserted into the plastic matrix. With others, their degradation products may not be completely benign; polyvinyl chloride is a well-known example. Because of this, some plastics cannot be incinerated and even slow degradation in landfills may result in the release of undesirable material. In these situations, the plastics must be disposed of in a controlled manner, much in the way that laboratory solvents or infectious waste must be handled.

The proper disposal of these plastics with undesirable properties is often thwarted by uncaring or ignorant laboratory workers who throw the item into the closest trash container rather than walk over to where the special trash container is located. While it is difficult to prevent the actions of an uncaring worker, laboratory management must include a discussion of proper disposal in its analyst training to at least minimize the effects of ignorance. When a laboratory introduces plastics that have special disposal needs, it should also introduce proper training.

Laboratory management needs to consider proper-disposal requirements, as well as training, to determine whether costs outweigh the advantage of using disposables. Often, laboratory management itself is ignorant of the need for special handling or disposal of these plastics. Their problematic properties are not widely advertised, but manufacturers who introduce these products into commerce should be responsible for informing the user community of the need for special procedures. This communication could take an approach that is similar to the way pharmaceutical companies use direction inserts.

Another problem with disposables is especially prevalent in the QC laboratory, where a large number of small items are used, ranging from pipette tips to small test tubes and Pasteur pipettes. When they are emptied, a relatively large volume of liquid remains trapped within, either from capillary action or simple surface adhesion. This results in a considerable amount of contaminating liquid often being present in the laboratories' trash receptacles. Novice analysts are taught to rinse reusable items before placing them in containers for eventual washing; but this is not done with disposables. In many cases, no attempt is made to empty the items before they are placed in trash containers.

Most laboratories have special procedures in place for collecting and isolating disposables that were exposed to radioactive isotopes, but these laboratories may not have procedures for isolating items that may be contaminated with equally problematic substances. Perchloric acid and halogenated hydrocarbons are often present in waste containers for disposables. In one laboratory, acetonitrile (methyl cyanide) fumes were continuously present as they evaporated from vials and pipettes in waste containers.

Just because items are disposable, the contaminants that travel with them may not be. There are many solvents and reagents used in the QC laboratory that are considered to be environmental toxins. Long-term familiarity may cause analysts to forget about the dangers posed by these materials, and periodic reminders may be needed. Once again, laboratory management must be aware of the properties of the material used in the laboratory.

Trusting Suppliers

Another issue with disposables is trust. Disposables were introduced by highly reputable manufacturers and distributors, which led to an unquestioning trust in the properties of disposables. The problem now is that the effort to save on costs has driven many reputable manufacturers and distributors to deal with suppliers who are not as reliable as might be desired. Many disposables are now outsourced to organizations where the distributor has little or no control over the quality of operations.

In QC laboratories, there is an unquestioning faith that disposable pipettes and other disposable measuring equipment are accurate, and that the manufacturer produces a highly uniform product from a process that produces an accurately marked item. But this is not necessarily true. Sometimes, the actual producer lacks a reliable and accurate process.

Pipettes used in the microbiology laboratory or in the manufacture of sterile products are routinely cleaned and sterilized by validated procedures with biological indicators included in the sterilization batch. When sterile pipettes are purchased, however, they are not randomly sampled and tested for sterility. There have been sporadic reports of microbiology laboratories where a sudden rash of positive test results has been obtained. If a laboratory should encounter a number of unexpected, positive, sterility test results, it would seem sensible to test a random selection of the disposable, sterile pipettes that were used. For that matter, how often have media fills failed because of the random presence of one or two contaminated pipettes that were used to transfer samples or media?

Other measuring equipment is routinely tested for accuracy and reproducibility before being used, but disposable pipettes are rarely checked. In one case, a laboratory was checking its spectrophotometer by measuring the absorbance and the wavelength of maximum absorbance of a carefully prepared solution of an inorganic salt. The linearity of the instrument at the maximum wavelength was checked by making a series of dilutions using a disposable 5 mL pipette and several disposable 1 mL serological pipettes. A plot of the results showed that the spectrophotometer was more or less linear, but the points did not fall along a straight line. Statistical calculations showed that, while linear, the readings were highly variable. The samples were read on a second spectrophotometer that confirmed the erratic readings. The serological pipettes that were used to prepare the dilutions were rinsed and used to pipette known volumes of water which were weighed. The results showed that far from pipetting a reproducible volume of 0.10 mL, the pipettes were delivering volumes ranging from 0.085 mL to 0.17 mL.

Another area of concern has to do with the composition of the disposables. Are they really made from the materials that are stated on the labels? Does the laboratory really know what materials are acceptable for its work? When glass vials are used as containers for products, especially parenterals, there are QC tests that must be done to verify the type of glass being used. For example, the United States Pharmacopeia contains tests for the acceptability of borosilicate and flint glass. There are situations where the properties of the types of glass are very important; what about disposable beakers and sample bottles?

Analysts and biochemists who deal with blood coagulation factors and membrane-bound proteins and enzymes are familiar with problems caused by surfaces that activate or adsorb material and produce changes in the apparent potency of preparations. Certain types of proteins are known to bind to polymers such as agarose, cellulose, and polyamides. Thus the composition of microtiter plates, pipettes, and test tubes could affect the outcome of tests.

An assay is often validated using disposables with a given composition. If the composition changes, there may be subtle, but real changes in the properties of the assay. Changes of this type are usually assumed not to affect an assay, and careful checking is not done.

Some people will now wave their hands about and insist that these cautionary tales are exaggerations of highly infrequent events. These people are certainly entitled to their opinions, but they are exactly that—opinions.

Years ago there was a commercial for a national, fast-food, hamburger chain in which an elderly woman asked repeatedly and querulously, "Where's the beef?"

In a GMP environment, the question becomes, "Where's the proof?"

Steven Kuwahara, PhD, is the principal consultant at GXP BioTechnology LLC, PMB 506, 1669-2 Hollenbeck Ave., Sunnyvale, CA 94087; Tel 408.530.9338, stevekuwahara@yahoo.com