Choosing a Bioanalytical Lab 101: Beyond Analysis

Choosing a bioanalytical lab can be daunting. For the uninitiated, knowing what is really important beyond just the analytical capabilities of any lab, can determine if a study will be executed with great trepidation or incredible ease.

Since choosing a lab to perform bioanlysis and biomarker development is a critical path issue for drug development, making the right choice the first time around becomes increasingly important to pharmaceutical and biotech companies. Finding a lab with a level of sophistication and high quality standards, technological expertise, and know how is a rigorous exercise – and yet an oft-overlooked detail that is frequently treated as an assumption.

So how do you know that the lab you choose will be the best option? Consider these five service elements that can make or break your efforts to achieve the right and best results.

1. Multiple technology platforms
Flexibility is a key element and one that enables a laboratory to develop and perform specialized assays.

Diversity in testing platforms enable a laboratory to provide an assay with adequate performance in sensitivity, specificity, selectivity and assay range, enabling the laboratory to best measure the molecular markers affected by the therapeutic. As an example, quite often immunoassays can be very sensitive and easy to set up, but they can suffer from problems with specificity and selectivity, and the assay range can often be limited. Knowing when to migrate to an alternative platform can make a difference in the characterization of a biomarker and lead to the collection of more meaningful data.

Some diverse technologies include LC-MS/MS, GC/MS, LC-MALDI-TOF/MS, immunoassay, and enzymatic assays. The choice of platform depends upon the purpose of the study and of the data being collected, a topic which will be further addressed later.

2. Regulatory compliance
What regulatory guidelines should your lab follow? GLP vs GLP-like? Is GLP overkill?

The crucial consideration here is the purpose of the assay. Are you collecting exploratory data? Are you determining a metabolic pathway? Will the data be used for a regulatory submission? Are the data being used as a primary endpoint? These are critical questions, and the answers to these will determine how rigorous regulatory compliance should be. Although clinical labs adhere to high precision and accuracy standards, GLP compliance sets the bar a bit higher, and is something that regulatory agencies will look for when submitting primary endpoint data. However, if you are collecting data to augment your out-licensing package, the rigors of GLP compliance, which often come at a high price, might not be necessary. All of these factors should be weighed when considering an assay. This is the basis of the term “fit for purpose”.

3. Customization
Having a bioanalytical assay menu can be meaningless if the assay does not measure the desired analyte at the desired range in the required matrix. The choice of an unsuitable assay can happen a great deal with low dose therapeutics that make small but measurable changes in the metabolic profile, or if a therapeutic down regulates the expression of a biomarker response to the point that it is below the level of quantitation. Similarly, if a molecular marker is up-regulated, the assay will need to have a broad enough dynamic range to accurately measure the higher results without serial dilutions that can often affect accuracy. High levels of certain biomarkers, in particular proteins and enzymes, need to avoid or address the “hook effect” that can plague immunoassays when results are above the level of quantitation. The lab you choose must be able to customize for therapeutic application and to a client’s needs, while also not losing sight of the assay limitations at the low and high ends of the calibration curve. Optimizing assay performance at one end or another is something that should be sought when the low or high end result accuracy is critical to the success of a study.

4. Validation
How will your laboratory validate its assay? In many cases it is as simple as purchasing a commercial kit and demonstrating precision and accuracy using standard commercial controls. For routine assays this is quite common and often acceptable.

But increasingly in pharmaceutical research, the search for the uncommon molecular marker can lead to companies seeking to validate assays for novel biomarkers that do not yet have consensus acceptance in the clinical community. When this occurs, how can an assay be “validated”? To what standards can the novel assay be compared?

“Validation” of an assay is done at two levels. The first is a technical validation that ensures that the lab is measuring what it is supposed to measure accurately and precisely. The second level of validation involves the demonstration of the usefulness of the biomarker and gaining consensus on its value as a biomarker, a process often described as “qualification”.

For example, for many years the regular measurement of fasting blood glucose was an accepted way of managing a diabetic patient. Glycohemoglobin emerged about 25 years ago as a way of measuring how well these patients were managing their disorder. Acceptance among health care providers was initially slow, but today glycohemoglobin measurements are an integral part of managing diabetic patients. And yet, even more sensitive biomarkers are being sought for diabetic applications, not necessarily to replace glycohemoglobin but as a complementary biomarker to assess clinical effects.

A novel biomarker for a particular indication has to both be measured accurately, and demonstrate that it is useful in the diagnosis or management of a disease, and then gain acceptance in the medical community (and in the case of pharmaceutical research, within regulatory agencies).

5. Sample Logistics
Expertise in sample logistics is invaluable because biomarkers can be unstable during sample transportation. A bioanlaytical lab must have a level of sophistication and in-house technical expertise to determine how a sample should be collected and how it should be transported. This capability is not as commonplace among laboratories as one might think. As the pharmaceutical industry increasingly looks to corners of the globe with treatment-naïve patient populations, this has become a critical area of expertise and a very important part of ensuring that the highly sophisticated, highly accurate assay that was developed will be used to analyze samples that have not deteriorated during transport. It is the age-old adage that laboratory scientists have heard since their first days on the bench: “Garbage in, garbage out.”

The lab you choose must know the numerous ways that samples are collected, prepared, stored, and shipped, and it must employ appropriate strategies depending upon the type of study. For a study with a single or limited number of sites, proximity to the testing laboratory can be advantageous, as sample deterioration during transport will be negligible if not eliminated. However, proximity of a lab for a specialized test is often not realistic, and for multicenter studies there needs to be an emphasis on training of personnel beyond the usual 15 minutes that is devoted to laboratory issues at Investigator Meetings. Clear instruction, telephone training sessions and the use of visual media to demonstrate proper technique can make the difference between obtaining meaningful data and collecting useless laboratory results, results that in all likelihood are quite accurate but because of problems with sample logistics, sample integrity was not maintained and the results are worthless.

However, what also needs to be considered is whether a biomarker that is highly labile is a suitable biomarker for a multicenter clinical study. If the risk of sample degradation is high, alternatives should be sought. Most contract bioanalytical labs do not have a lot of experience moving samples from multiple regions all over the world and will rely upon highly expensive courier companies to compensate for limited experience with sample logistics. Conducting transport studies to verify proper technique at a site and sample integrity during transportation is something that is done increasingly, and it could provide guidance regarding the choice of courier service (e.g.., premium service vs. routine service). If the data being collected is critical to a submission, this is a small investment, and if included with the regulatory submission it can actually enhance the credibility of the results obtained, especially for novel biomarkers.

About Eurofins Medinet
Choosing a laboratory that can provide these five elements – multi-technology platforms, regulatory compliance, customization, validation, and sample logistics expertise – is critical to the success of your study. At Eurofins Medinet, not only are we proud to offer these service elements, but our bioanalytical team works hand in hand with the core global central laboratory, which has over 20 years of experience in laboratory testing to support clinical trials.

Eurofins Medinet is a leading global central laboratory dedicated to providing fast, efficient, and reliable laboratory testing services to make your drug development efforts a success. Eurofins Medinet provides preclinical and Phase I-IV trial management and laboratory testing. We uphold the highest quality standards in our CAP, CLIA, ISO, and GLP certified laboratories worldwide.

Eurofins Medinet integrates a broad range of laboratory services, including:

• Full service laboratory testing menus for preclinical and Phase I-IV trials, including hematology, biochemistry, coagulation, immunochemistry, urinalysis, infectious disease, flow cytometry, and PK/PD testing.

• Microbiology consultation and laboratory testing to support early stage drug development and clinical trials, including molecular characterization, molecular typing, lead compound screening, resistance development, bactericidal activities, Post-antibiotic effect, interpretive breakpoint determinations, development of disk diffusion and MIC methodologies.

• Biomarker services including biomarker analysis, specialized validation for clinical trials, and therapeutic drug monitoring. Eurofins Medinet also provides GLP reporting to support bioanalysis.

• Bioanalytical services including method development and validation, metabolism and toxicology, analysis of clinical trial protocols, as well as PK/PD testing.

• Full service trial management including project and data management, logistics support services.

Having a broad range of expertise within one organization is a great advantage for our clients.

Mickey O’Brien is a PK/PD Specialist at Eurofins Medinet. He and the Biomarker Group at Eurofins Medinet assist companies with biomarker strategies for preclinical and clinical development. He has over 30 years of experience in clinical and bioanalytical laboratories, and has diverse experience with drug development processes from discovery and lead characterization through launch and post-marketing strategies. He has a Baccalaureate degree from Fordham University and a Masters degree from New York University.