Choosing the right central lab

In the past few decades, China and other Asia- Pacific countries have become popular locations for clinical trials. The trend towards holding studies in the region doesn’t appear to be slowing down either, with analysts estimating that the current $7.6bn contract research organisation market will grow to $11.9bn by 2025. That popularity has been at least partly driven by the relatively low market rates of the clinical trial workforce. Some of the costs can be 25–35% lower than they are in the US and some European countries, says Michael W Young, a principal at biomedwoRx: Life Sciences Consulting. This is particularly the case, he says, in the areas of “data management, biostatistics and central lab testing, including bioanalytics”.

Another consideration is that if a drug is designed to be used for a condition that affects a particular ethnic population, it makes sense to have that population well represented in trials. Regulatory bodies, says Honggang Bi, head of APAC at Labcorp Drug Development, “may require populations from their own region to be included in the trial so they can review the data with better confidence”.

Global central labs have systems worked out

When it comes to choosing a central laboratory, there are good logistical reasons, Bi points out, for selecting one near the patients being studied. He cites the eruption of the Eyjafjallajökull volcano in Iceland in 2010 as an example of an event that disrupted the ability to transport samples from different locations. Covid-19 is a more recent example of an unanticipated event that has, says Young, “impacted clinical development in multiple ways”. This has included difficulties moving samples between countries that have closed borders, such as New Zealand. “So, what does that mean in terms of sample accrual – samples going to central labs which may not be in New Zealand?” he asks. “There are clearly problems in just maintaining sample integrity,” he notes. “This is one of the reasons global central labs make so much sense, because they’ve got those systems worked out.”

So, what are the key factors sponsors should consider when choosing a central lab? While there are some companies dedicated solely to providing central laboratory services, there are also a number of contract research organisations (CROs) that provide central lab services as part of their full-service model. One of the advantages of opting for a CRO is the ability to integrate data from different services. For example, says Bi, bioanalytical measurements are typically carried out in a separate laboratory and are, therefore, often not fully integrated with the central lab work. A full-service CRO is more likely to be able to offer that integration.

Local CROs, such as ChemPartner and ClinChoice who are headquartered in the region, “do outstanding work at significantly lower cost”, says Young. Because these are “local to the Asia Pac ecosystem”, he adds, they are “quite familiar with the regulatory scenario that exists, for instance in China, which is somewhat different than other countries”.

Harmonisation is crucial

Several global CROs also offer central laboratory services in Asia-Pacific countries to sponsors carrying out clinical trials in the region. These include players such as Parexel, PPD and Bi’s own company, Labcorp. These companies have the advantage of size; larger laboratories, says Bi, will have the scale to support a number of different trials. “[Labcorp has] thousands of assays or methods available, but when you go to a smaller player, they may have 100 or 200 assays,” he adds. Similarly, the company’s staff has a wide range of scientific expertise.

As well as lacking a breadth of scientific expertise, smaller laboratories may not be able to scale to handle thousands of samples, argues Bi: “If you look at the latest oncology trials, a trial could cover ten or 15 indications with multiple legs. That represents tremendous complexity.” He points out that the lab will need to be able to analyse multiple sets of data: “If you don’t have the means to handle that, it will be a nightmare.”

Young notes that much of the central lab work being done in countries outside the US and Western Europe “has coalesced from groups of independent clinics or smaller university, or hospital clinics”. Because central labs are “largely involved in making sure that all of your tissue samples and all of your data collection are collected and analysed in a uniform manner”, he says, the consistency and comparability of testing methods and equipment across labs is crucial. “Small variations in equipment and testing standards, concentration standards of reagents, can effectively mess up your work.”

In a global trial, therefore, harmonisation is crucial, Young adds. Sponsors will want to check whether the laboratory has accreditation from the College of American Pathologists or meets the requirements of the Centers for Disease Control and Prevention (CDC) or the National Glycohemoglobin Standardization Program (NGSP). The lab will also need to meet the local requirements of the ministries of health in the different countries.

Be aware of regulatory processes

In cases where the sponsor is initiating a large global programme that might run for several years, says Young, it can be worth carrying out an audit or at least reviewing existing audits of the central labs involved. “You want that audit to not only address protocol and internal standards, but to take a look at financial stability and look at not only the technology but also the technicians that are involved,” he says. It should also ask questions such as: “Have there been any financial improprieties? Have there been concerns about any of the personnel or the leadership of that particular central lab?” Factors such as these “contribute to the operational norms, which are important to maintaining good relationships”.

Sponsors should be alert to the differences between the countries in the region, says Bi. He points out that Labcorp has only one central lab in the US and one in Europe, but has three in Asia- Pacific (in Singapore, China and Japan). “China has very strict import/export rules on biological sample shipments, so it’s not that easy to go in and out, whereas Singapore is an open port, so you can easily do this without any time delay,” he explains. Anything imported into or exported from China requires an extra few days. “You also need to submit for approval, probably a few weeks or months in advance,” he adds. That would make it extremely logistically difficult if the trial was being run in China, but the laboratory was based in Singapore.

Regulatory processes are very different in many of the Asia-Pacific countries, so it’s worth choosing a central laboratory partner who is experienced at managing the regulatory approval process. “The biggest thing when you’re doing drug development is time, time, time,” says Bi. Time can be saved by launching processes in parallel. Even when steps cannot be carried out in parallel, they can usually be performed in a staggered way to reduce timelines, he says. Sometimes the clinical trials application or Human Genetic Resources Administration of China (HGRAC) application comes back with a request for supplemental information. “Every time you do this, that delays the process,” says Bi. “Our goal with clients is always to accomplish one-time submission and one-time approval, so that also saves a tremendous amount of time.”

A global petri dish

Finally, when choosing and working with partners in China or other countries in Asia-Pacific, don’t forget the significance of cultural factors.

Bi says that in the past five years “tremendous progress” has been made in China, but certain nuances still exist. For example, he says, in Western countries, if you need to have, for example, an ethics committee meeting, you will simply call a meeting: “Whereas in China the site will say, ‘We do it only once a month,’ so you need to follow that rule. If they [the meetings] are every first Tuesday of the month, then you just have to prepare everything ready to go on the previous Friday.”

It’s helpful to remember, adds Young, that in most Asian cultures a “much higher value” is given to professional hierarchy than in the West. If something goes wrong, he says, “You need the ability to get to the right people, have the right conversation and do this in a manner in which you can affect the change that you’re looking for. Managing central labs at distance is not just a physical distance, it’s also a cultural distance, so you can’t just mail it in.”

Perhaps those cultural differences are less important than they used to be. The pandemic has taught us that we’re a “global petri dish”, says Young, and we need to work together to solve global challenges. Between the “harmonisation and standardisation” that central labs provide and the favourable economics of conducting trials in the Asia-Pacific region, he believes there’s a strong opportunity for clinical development as the number of studies continues to increase.