Pharmaceutical Industrial Hygiene

This guide provides the tools you need to compare surface sampling kits based on price, customer service and quality. With the information presented here, you should be able to make a well-informed purchasing decision, and one that will help you meet the expectation of USP 800 and medication compounding reviews by the Joint Commission.

The 2017 USP Compounding Compendium’s General Chapter 800 (USP 800) on the handling of hazardous drugs (HDs) in healthcare settings, first published in February 2016, had gone into full effect on December 1, 2019. USP 800 contains guidelines for the sampling of hazardous drugs on surfaces to help you improve environmental protection, patient safety and worker safety in health system workplaces.

The Joint Commission launched its Medication Compounding Certification program in February 2017 and awarded its first certificate under the program the following April. Researching and evaluating the different USP 800 HD surface sampling kits that are available will better prepare you for your next review.

Whether you are ready to buy a kit and start sampling, or just doing your research for when the time comes, this guide will help you by simplifying a difficult decision, arming you with some good questions and saving you time and effort on your way to USP 800 compliance.

How to Choose the Best Kit

Before deciding on a kit, take a step back and remind yourself why you are buying it in the first place. USP 800 surface sampling is best performed according to a sampling plan, to help identify, assess and control the presence of residual HDs on workplace surfaces in and away from controlled environments.

There have been several studies over the last few decades that have made connections between surface contamination and the potential for occupational exposure to HDs. Therefore, USP 800 recommends sampling surfaces to help improve the health and safety of those working with and being around HDs.

If surface samples of HDs have not been previously collected at your facility, your first round of sampling results will become the baseline for comparing against future rounds of sampling results. This is an important part of the sampling plan, since it will allow you to demonstrate the effectiveness of improvements made to your exposure controls.

It is Not Just a Kit

Using a surface sampling kit is an easy and convenient way to collect samples of potential HD contamination on workplace surfaces. Kits typically contain all or most of what you need to collect samples and send them to the laboratory for analysis, including the sampling media, shipping supplies and peripherals such as forms and instructions.

The main benefit of a kit, as opposed to stand-alone media for single HDs, is that a kit makes it easy for you to have individual samples analyzed for multiple HDs. This type of analysis is sometimes referred to as a ‘scan’, and is made possible by the laboratory’s use of a highly sensitive and specific analytical technique called High-Pressure Liquid Chromatography with tandem Mass Spectrometry, or LC/MS/MS for short. A laboratory’s ability to analyze for multiple HDs on a single sample is a clear indication that LC/MS/MS is being used, and the advantage is that very small amounts of HDs can be detected, identified and quantified while virtually eliminating the risk of obtaining false positive results.

Given that the analysis of surface samples is technically advanced, it is important to realize that you are not just buying a kit. You are also buying laboratory analytical services. Therefore, the performance of a kit is directly related to the quality of the analysis and service you receive from the laboratory.

The question then becomes how best to choose the right kit and the right laboratory to perform the analysis. There are a number of criteria you can base your evaluation on. To take some of the guess-work out of a decision like this, here is a run-down of some important points for you to consider:

  • Laboratory accreditation
  • Analytical capabilities
  • Pricing
  • Ease of use
  • Customer service

The single most important factor to consider when choosing a surface sampling kit is whether or not the laboratory performing the analysis is accredited by the American Industrial Hygiene Association (AIHA) and International Organization for Standardization (ISO).

The association’s Industrial Hygiene Laboratory Accreditation Program (IHLAP) is specifically designed for industrial hygiene laboratories that are involved in the analysis of samples for the evaluation of workplace exposure, and includes ISO/IEC 17025 accreditation (competency standards for carrying out tests and calibrations).

The program sets strict standards for the accredited laboratories, which control their operations in terms of the competency of personnel, validity of analytical methods and assurance of test data quality, to name but a few.

The main reasons why it is so important that you use AIHA/ISO accreditation as the first benchmark for laboratory comparison are:

  • Improved reliability and accuracy of results
  • Minimized risks through assured competency
  • Recognized impartiality of testing

Analytical Capabilities

After establishing laboratory AIHA/ISO 17025 accreditation, the next step is to assess the analytical capabilities of the laboratory. Examples of analytical capabilities include: how many and which HDs you can test for with a standard kit, the limit of quantification (LOQ) of the analysis and what other non-standard HD analyses are available from the laboratory.

Multiple HDs per sample

Surface sampling kits are convenient because you can use them to test for multiple HDs using a single sample, meaning that you are able to take fewer samples saving you both time and money.

When shopping for a kit, keep in mind that it is better in terms of pricing and ease-of-use if a kit has a relatively long list of HDs that can be tested on a single sample.

When contacting a laboratory for information, it will help you and the laboratory tremendously if you already know which HDs you are looking to test for. If an HD you are interested in is not on a kit’s list, be sure to ask the laboratory about it, since some laboratories may have capabilities beyond what is included in the kit.

Platinum-containing HDs

Another important consideration for selecting a surface sampling kit is whether or not you wish for your samples to be analyzed for platinum-containing HDs. The sampling for and analysis of platinum-containing HDs can be a confusing aspect of a kit purchasing decision. This is because, it is sometimes not immediately clear whether or not the analysis of platinum-containing HDs is performed using the advanced LC/MS/MS technique mentioned earlier or a different analytical technique called Inductively Coupled Plasma with Mass Spectrometry (ICP-MS).

Where ICP-MS is being used by a laboratory, its prices for the analysis of platinum-containing HDs may be lower, structured differently and/or offered as an add-on. Furthermore, the laboratory may require you to sample for platinum-containing HDs in a different way, i.e. by collecting a dedicated sample from a dedicated spot. In cases like this, you could potentially be doubling the number of samples you will have to take, or cutting the sampling capacity of the kit in half.

To add to the complexity, a laboratory using ICP-MS for the analysis of platinum-containing HD samples may also report its results differently to other HDs analyzed by LC/MS/MS. This is because ICP-MS cannot distinguish between the three most common platinum-containing HDs: Carboplatin, Cisplatin and Oxaliplatin. Therefore, regardless of which one you asked for, the laboratory using ICP-MS will give you results for ‘total platinum-containing HDs’, expressed as the one you asked for.

The laboratory using LC/MS/MS for the analysis of platinum-containing HDs will be able to identify and quantify each of the three platinum-containing HDs. The use of LC/MS/MS also virtually eliminates the risk of obtaining false positive results for platinum containing HDs, which is a problem that is encountered more frequently with ICP-MS. Note that even if a laboratory advises you that platinum-containing HDs can be collected on the same sample as other HDs, this is not a guarantee that LC/MS/MS is used for the analysis and reporting of platinum-containing HD results. It is therefore strongly recommended that you ask for platinum-containing HD samples to be analyzed by LC/MS/MS.

Limit of Quantification

Comparing the limit of quantification (LOQ) between multiple kits can sometimes be confusing. This is because the LOQ is directly related to both the sensitivity of the analytical technique and the surface area being sampled. Problems arise when you try to compare LOQs presented in different units of mass per area, such as nanograms per square centimeter (ng/cm2) and nanograms per square foot (ng/ft2).

The simplest way to compare LOQs between kits is in mass per sample rather than mass per area. To compare one kit’s LOQ of 5 ng/sample (of 100 cm2) to another kit’s LOQ of 10 ng/ft2 for example, you have to present the latter in ng/sample. If you sample an area of one square foot, 10 ng/ft2 is simply equivalent to 10 ng/sample, which then makes the comparison simple. However, if you convert both kits’ LOQs to mass per square centimeter, based on the prescribed sampling area for each kit, the LOQ converted from mass per square foot will appear disproportionately lower because of the larger sampling area.

Another good reason to retain LOQs and analytical results in the unit of mass per sample applies to the comparison of samples taken from surfaces that are irregular or of limited surface area, such as door knobs, computer mice and keyboards. For these and similar surfaces, you will therefore have results in mass per door knob, per mouse and per keyboard effectively, which helps to keep things simple.

HDs Not on the Kit’s List

If you are looking for an HD that is not covered by a kit, you will first need to check if the laboratory offers it as part of its portfolio of analytical methods. If it does, then you will need to consult with the laboratory on how to sample it. Each kit contains special sampling media, which may not be compatible with an HD that is not on the kit’s list. Sampling an HD that is ‘off-menu’ so to speak, may require different sampling media and/or special handling for example.

Pricing

Knowing which HDs you want to test for, and having selected an AIHA/ISO 17025-accredited laboratory that has the analytical capabilities you need, you are ready to make a price comparison.

Laboratories typically each use a different pricing structure and it is therefore difficult at times to make a comparison. Common for scan-type analyses is a price for the first sample with one HD, plus a smaller price increment per sample for each additional HD. Therefore, when comparing surface sampling kits, be sure to ask the laboratories for a price for the same number of samples for the same number of drugs. The laboratory’s ability to test for multiple HDs on a single sample is a great money-saving feature, far more cost effective than testing for one HD per sample.

As mentioned earlier, be sure to advise the laboratory if you intend to collect samples of platinum-containing HDs, since prices and LOQs for these may be different. As a general rule-of-thumb, a lower and/or separate price for the analysis of platinum-containing HDs may be indicative of a less sensitive analytical technique being used by the laboratory, potentially resulting in a higher LOQ.

One simple way to make a price comparison between multiple kits is to assume that you are collecting one sample from each of the six locations recommended in USP 800. You can then go one step further and assume that you will want to have each of the six samples analyzed for the same six HDs (excluding platinum-containing HDs), effectively ending up with what you could call a “6 x 6”.

This may not be what you ultimately end up doing, but will simplify your decision-making. It helps you identify which kit you want to go with now, so that when you are ready to do the sampling, you will have made a decision and are able to act fast.

Ease-of-use

There are a number of elements that determine how easy you will find it to actually use a surface sampling kit. Since this can be somewhat subjective, here is a short-list of points you can use for your own comparison:

  1. Number of HDs per sample
  2. Sampling instructions
  3. Sample collection
  4. Sample shipping
  5. Turnaround time (TAT)
  6. Trend reporting

Number of HDs per sample

A good rule-of-thumb is: the longer the list of HDs per sample, the better. As you have seen, more HDs per sample generally means lower pricing, since you can take fewer samples and there is less chance of having to order ‘à la carte’. The ability for you to be able to take just a single sample at each of your chosen sampling locations is a real benefit.

Sampling Instructions

If you have not collected a surface sample before, it is natural that you will want to familiarize yourself with the sampling procedure, so that you can be confident and comfortable when you actually go out and do it. Not only that though, it is also very important to minimize errors and to submit viable samples for credible results. Therefore, anything you can do to prepare yourself beforehand will pay off.

From a kit purchasing standpoint, you will want to check the resources that a laboratory is making available to you on its website. These might include:

  • Video of the sampling process
  • Answers to frequently asked questions
  • Written instructions

Sample Collection

The contents of surface sampling kits will all be a little different, and the sampling instructions will all be different as well. So how do you determine which kit is easiest to use? One way is to compare how laboratories want you to delineate the sampling area. Follow this up with comparing how the actual sampling is done, and you will have a good understanding of what will work best for you.

It is recommended to collect samples with the same surface area every time, typically 100 cm2 or 1 ft2. This is to make it possible for you to compare the analytical result between samples, especially if results are expressed as ‘per sample’. Arguably the easiest way to delineate the sampling area is by using a pre-sized template. Assessing how laboratories want you to get the HDs off a surface and onto a sample, referred to as ‘surface recovery’, is another good way to establish the ease-of-use of a kit. Kits typically come with sampling media, consisting of swabs or wipes and a ‘wetting agent’. The typical procedure is to wet the swab or wipe with the wetting agent, and to make two passes across the entire surface within the delineated sampling area (one horizontally and one vertically).

A review of the resources the laboratories are making available to you on their website, will help you decide which sampling method works best for you.

Sample Shipping

If you need more validation to support your kit purchasing decision, ask the laboratories about the stability of the HDs once they are on the swabs/wipes in transit on their way to them for analysis, which is referred to as ‘storage stability’. Check if the laboratory provides some kind of sample thermal protection, designed to protect samples against temperature fluctuations, which is a good indication that it has assessed what is needed to receive viable samples, even in unusual circumstances such as shipping delays and extreme weather conditions.

Turnaround Time

How quickly a laboratory can get you results from the time of sample receipt is also a useful way to compare surface sampling kits. It is worth remembering that turnaround times are not guarantees, but rather estimates based on historical averages of what the laboratories can achieve, taking into consideration available resources at any given time. Knowing this, you can compare surcharges for rushed analytical services if you think you may need results more quickly.

Trend Reporting

Surface sampling is ideally performed according to a sampling plan, and USP 800 recommends that it is repeated at least every six months, so that you are then able to assess the effectiveness of any past action taken as part of the plan in order to control the source of HD contamination.

A kit purchasing decision is therefore best made alongside a well-thought-out plan. Before deciding on a particular kit, you may wish to consider what type of purchase you are looking to make. For example, are you shopping for a single facility or for a group? This is relevant because sampling for multiple HDs, at several locations, at multiple facilities, twice a year will quickly build up a large amount of analytical data.

For your first round of sampling, it would be reasonable for you to ‘expect to detect’ the presence of HDs on workplace surfaces, meaning you should not be surprised to get positive laboratory results indicating HD surface contamination. If or when you do identify contamination, you will then be in a position to do something about it, thereby improving the health and safety of those who work with or may come into contact with HDs.

On completion of your first round of sampling, the analytical results reported by the laboratory essentially create your baseline for HD surface contamination at your facility or facilities. Given that USP 800 does not prescribe a threshold limit for levels of HD surface contamination, your goal then becomes to demonstrate a reduction in HD surface contamination through corrective action, possibly as far as achieving results below the laboratory’s LOQ.

Most laboratories will email you the results in PDF format as standard. However, analytical results on a PDF document do not allow for an easy extraction of data-driven insights. Before you purchase a kit, it is a good idea to ask the laboratory if they can present your results on a spreadsheet as a minimum, so that you can more easily work on the data to identify trends.

In making a kit purchasing decision, know that some laboratories offer optional services for the reporting of trends in analytical results.

Figure 1: Trend Reporting

USP 800 Trend Reporting

Customer Service

As with any purchase, the experience of customer service is a subjective one. When contacting a laboratory for more information about a surface sampling kit, there are a number of good questions you can ask.

Here is a short-list of questions to help you in your decision-making:

  • Do I have to pay for the analysis up-front or can I pay when I get the results?
  • Do you offer training to groups, for example in-person or live/remote training?
  • Tell me about the history of your laboratory.
  • What advice can you give me about my surface sampling plan?
  • How long have you serviced the pharmaceutical industrial hygiene marketplace?

Since price, kit quality and customer service will likely be the most important decision-making criteria for you. The answers you get to these questions should help you to get a sense of the level of service you can expect from the laboratory going forward.

Summary

In summary, putting price and customer service aside, here are the five main benefits that make up the best quality kit:

  1. Laboratory AIHA/ISO 17025 accreditation
  2. Largest number of HDs possible per sample
  3. Platinum-containing HDs analyzed by LC/MS/MS
  4. Lowest LOQ in mass per sample
  5. Trend reporting options