As the pharmaceutical industry grows further toward an outsourcing model, more focus is being placed on the capabilities of the analytical laboratories within the Contract Research Organization industry. Whether the analytical (or bioanalytical) laboratory is a standalone facility or part of a much larger global organization, the emphasis on the quality, compliance and demonstrating a deep understanding of sponsors’ comprehensive laboratory needs is fast becoming a mandate for the whole industry. In the past it may have been acceptable for a contract house to offer a focused analytical service as a standalone service. Today however, the analytical laboratories are integral to all outsourcing activities and are playing a much larger role in guiding and optimizing drug development needs.

Additionally, CRO laboratories are increasingly being called upon for their expertise in an ever-expanding array of therapeutic areas and molecule types. For example, many more companies are performing work on biologic drugs and natural products than ever before. In order for them to remain competitive and act as true partners in these fields, they need to show their investment in the necessary scientific experts and tools. 

With this, the contract analytical labs of today are being scrutinized in more detail than ever by their sponsors, whether it be during pre-selection, in-progress or post-contract audits. 

In order for a laboratory to reap the benefits of the growth in outsourcing, it is important to showcase itself so that sponsors can see that the CRO has the necessary capabilities to partner effectively. It is important for any contract laboratory to show the appropriate scientific expertise, a clean, well-laid-out laboratory, good work practices (that is, scientifically robust, compliant and efficient) and above all modern, state-of-the-art instrumentation and data management systems.

Previously, it was acceptable for CROs to use older analytical equipment; however, today’s sponsors expect that contract analytical laboratories operate using the same caliber of analytical solutions that the pharmaceutical companies themselves use. In fact in some cases, sponsors are defining the particular systems that must be used in order to align working practices and make technology transfer and data sharing easier. Without this level of equipment, laboratories may lose out on new contracts to more forward-thinking competitors.

In addition, laboratories need to consider their internal business process and factor in purchases with this. For example, if the CRO operates on multiple sites, it may have harmonization activities that dictate either the selection process or the instrumentation itself. Lean Six Sigma, productivity controls, and the need to do more with less are all factors that may be considered during the selection process. Internal quality and/or regulatory requirements may also have a factor in this choice. 

With all of this being said, what does a contract analytical laboratory (and potential sponsors) need to look for when selecting instrumentation and data systems for the laboratory? We will explore the solutions that CROs need to consider in order to stay a step ahead of the competition.

Liquid Chromatography

Liquid chromatography is prevalent at all stages of the drug development process in pharmaceutical companies and CROs that support them. While High Performance Liquid Chromatography (HPLC) was once the only option available to these companies, many companies are now moving to Ultra Performance Liquid Chromatography (UPLC) to enable themselves to gain a competitive business advantage. Significant cost savings have been demonstrated, whether it be through reduced solvent use — some labs have saved more than 80% on their chromatographic solvent use — or the ability to get results faster, while also providing better scientific data that the sponsors and regulators require. UPLC is the future and some sponsors are insisting on this new technology moving forward. 

At the same time, many laboratories still have legacy HPLC methods to deal with, so it becomes a challenge to balance the needs of deploying various types of methods. This can be overcome with the latest generation of instrumentation, which allows both HPLC and UPLC methods to be run on the same chromatographic system without reconfiguration, hence allowing greater flexibility. This enables the laboratory to operate with smaller numbers of instruments, reducing the overall laboratory cost basis as a means of boosting profitability. Additionally, some of these instruments offer the ability to switch columns and solvents without operator intervention, allowing more than one method (and therefore sample batch) to be run on one instrument in one day.

Factors that laboratories consider when choosing their LC systems are speed, sensitivity, ability to handle a wide range of molecules, and system robustness. Is the LC instrumentation going to be used alone? Or does it need to interface with other instruments (such as mass spectrometers)? All of these should be considered during the selection process.

Mass Spectrometry 

Liquid chromatography interfaced with a tandem quadrupole mass spectrometer (LC-MS/MS) is the most prevalent technique used within contract labs performing quantitation of low levels of analytes whether it be for impurities in API and drug products, or for bioanalytical purposes. The latter is often performed to determine the levels of drug and related metabolites present in samples generated from preclinical toxicology tests, as well as clinical trials. The requirements in this area for high throughput and low detection limits demands the use of UPLC coupled with tandem mass spectrometry (UPLC-MS/MS) to In addition to the separation speed benefits, the sharper peaks that are obtained from UPLC-MS/MS allow lower Limits of Quantitation (LOQ) than have traditionally been achieved when using HPLC-MS/MS. 

With these more sophisticated and flexible tandem quadrupole platforms, in addition to enabling high-quality analyses of extremely low concentrations, it is also possible to routinely use smaller sample volumes as well as employ more cutting-edge approaches, such as dried blood spot sampling, for these analyses. This allows for the use of fewer animals in toxicology work, and also reduces the costs associated with shipping thousands of frozen samples to bioanalytical laboratories.

Despite this power and sophistication, advancements have been made in other areas of mass spectrometry, such as the ability to rapidly change ion sources with no instrument down time, building in more ease of use functionality with automated system checks, calibration, and method development. All of these factors enable a CRO laboratory to increase productivity and profitability though generation of better data faster, yet allowing an easier route of entry for non-expert users.

Informatics

Data systems are critical to the success of the analytical laboratory and in fact are essential for the control, data collection, and results generation of the instrumentation the labs are using. There is a wide variety of different data systems available, from simple workstation systems that support a single chromatographic instrument, to large enterprise solutions that operate across multiple laboratories (potentially across the globe) within an organization. In all cases, the strict regulatory compliance needed for data systems (including 21 CFR Part 11) requires careful thought and consideration. 

There are numerous factors affecting a laboratory’s choice of chromatography data system.
However, in this field more than any, there is a need for a single harmonized platform driving the selection of data systems. For example, regulatory requirements for data systems have driven most contract laboratories to harmonize on large enterprise chromatography data systems that control and collect data from a wealth of different chromatography systems from multiple vendors. Standard-izing on a single platform such as this brings significant benefits to the contract laboratory. This allows large labs to train their staff on one data system, allowing them to be more productive earlier, and allow all chromatographic data to be retrieved, reviewed and archived centrally. 

In all cases it is important to assess whether the functionality of an informatics system can help automate and drive a productive workflow in the laboratory. It is possible to drive workflow through acquisition templates, reporting standards, review processes, etc., which all allow the operators to work in a productive and more complaint manner. Also, is there functionality that allows easier sharing of data with the sponsor? Does the data system allow for easy investigations, allowing unexpected events to be fixed efficiently and in a compliant manner? Some data systems can help drive method development and validation activities within the same system, preventing potential compliance issues associated with moving data from one platform to another. 

Other Data Management Systems

One of the major challenges in working with an analytical laboratory is storing and retrieving data efficiently, especially when the data can be generated in many forms, such as manual data, date from pH meters, balances, etc., in addition to the chromatographic instrumentation. Solutions are now available that allow the capture of all of this information electronically, direct from the source, and also allow the capture of manual data through electronic notebooks. Once this data is captured, it is stored into a fully searchable archive. In addition to capturing all data, these solutions can automatically place it into report templates that allow access to the originating raw data. 

These scientific data management systems bring significant business advantages, allowing workflows to be directed from receipt of sample, through the sample preparation process, interfacing with the data collection system, and formatting and presenting results in flexible, custom-built reports that can be tailored to laboratory demands. This allows higher productivity in the workplace, reduces the risk of human errors, and means reports can be transmitted to the customer faster than ever. This brings significant advantages to both the contract laboratory and the sponsor. 

Installation, Validation and Servicing

One major factor that should not be overlooked when selecting instrumentation and informatics is the vendor support mechanism required. The support mechanism should be considered for installation, qualification/validation and also routine service support. On many occasions, a contract laboratory may purchase a piece of equipment specifically to meet the demands of a project. In order for this project to proceed quickly, there is a need for the purchase order to be handled quickly, the instrument to be delivered and installed as soon as possible, and the qualification to be performed immediately in order for the equipment to be released into production use.

When it comes to equipment and software qualification or validation, does the vendor have services to support this? 

For example, does the vendor assist with writing of or even provide testing scripts? Does it provide this as a service? Some vendors now sell this as an automated service that allows a laboratory to have new equipment or software up and running quicker. Most quality vendors offer this service and will help you plan the introduction of the new solutions in your laboratory from initial install through to routine use. 

It is also important to ensure that the vendor will provide all the necessary documentation for the services they offer. The contract lab is required to maintain these records and must be able to retrieve them to show to customers and regulators during audits.

Of course once the equipment is installed and in routine use, all laboratories will want to minimize the downtime associated with either unscheduled or scheduled maintenance. In all cases the laboratory will need to know that the vendor has a good service team available, one that is responsive to needs and has the necessary parts available to maintain the instrumentation as required. 

In addition, it is even possible for some vendors to provide business metrics, such as instrument utilization and productivity reports, through interrogation of the data systems on site. This allows hard data to be used by the contract lab to drive justification for instrument purchases or to drive workflow changes to enhance laboratory productivity. This partnership with the vendor can allow significant business benefits for both the contract laboratory and their sponsors.

Looking to the Future

As we look to the future, we see that technologies and software will become more readily accessible in much the same way that we see smartphones and tablets offering more functionality within the consumer products arena today. For instance, informatics systems will become more inclusive, offering more functionality across more application areas 

in an easier-to-use manner. We will see chromatography and mass spectrometry data combined with targeted data management tools all on the same enterprise-wide system. This will bring huge benefits for the laboratories that implement them. 

In this brief article, I have presented some of the many factors to consider when choosing and purchasing instrumentation and software for the CRO analytical laboratory. In an industry where customer relationships count, it is important that the choice of analytical solutions and services be made on sound business and scientific decisions. This allows the CRO enhance its scientific expertise and allows the sponsor to get quality data and reports quickly, efficiently, and in a compliant manner that allows the CRO/sponsor partnership to flourish.  

Dominic Moore is senior manager, Business Operations, Pharmaceutical and Life Sciences, Waters Corp. He can be reached at dominic_moore@waters.com.