Clinical Trial Monitoring of IVD Devices in China. Overcoming challenges with strategies for success

Dr. Caoifa Dougan
Global Clinical Trial Monitoring Team Leader

Dr. Shuainan Hu
Global Clinical Trial Monitor

Introduction

With the advancement of Precision Medicine, Companion Diagnostics (CDx) and Clinical Trial Assays (CTA) are increasingly utilised in Global Clinical Trials to guide subject eligibility for the targeted treatment of malignancies and chronic diseases. In 2024, CDx have an estimated market size of 7.74 billion with expected growth to reach 13.90 billion by 20291, demonstrating a marked increase in CDx regulatory approvals.

In order to ensure CDx are accurate and reliable there is a movement towards Global Clinical Trials occurring in several countries concurrently, including China, which enables data acquisition from diverse patient populations.

In response to this, regulatory authorities have produced several guidance documents to align the regulatory requirements for use of CDx and CTA globally, which also prevents duplication of effort across countries.

ICH Good Clinical Practice (GCP) E6(R2), European Union (EU) Regulation on In Vitro Diagnostic Medical Devices 2017/746 (IVDR); ISO 20916:2024 In Vitro Diagnostic Medical Devices, Clinical Performance Studies using Specimens from Human Subjects, Good Study Practice; and 21 CFR Part 812 Investigational Device Exemptions (IDE) are examples of these guidance documents.

Furthermore, these guidance documents stipulate the requirement for Monitoring Clinical Trials where an investigational device (CTA or CDx) is utilised in an interventional manner.

GCP defines Clinical Trial Monitoring as “The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s)”². Additionally, Clinical Trial Monitoring requires flexibility and adaptation dependent on each Clinical Trial and location, for example, restrictions on subject data dissemination outside of China.

“Clinical Trial Monitoring requires flexibility and adaptation dependent on each Clinical Trial and location, for example, restrictions on subject data dissemination outside of China.”

Challenges of Monitoring CTA and CDx Devices in China

Almac Diagnostic Services is an established Clinical Trial Assay (CTA) and Companion Diagnostic (CDx) provider globally, with specific knowledge and experience in China.

There are several key challenges Biopharma Sponsors face when conducting CTA and CDx trials in China:

1. Clinical Trial regulatory requirements are governed by the National Medical Products Administration (NMPA), which differ substantially from global regulatory requirements (US (FDA), EU (EMA), UK (MHRA)). Additionally, in 2019 China introduced The Human Genetic Resources (HGR) regulation, which applies to all human genetic materials and human genetic information within China³.
2. Genetic materials are defined as “organs, tissues, cells, etc. that contain human genome, genes and other genetic materials”³. In accordance with HGR regulations, foreign entities are prohibited from collecting Chinese genetic materials. Additionally, genetic material collected in China cannot be shipped outside China.
3. Genetic information is referred to as “data and other information generated” from genetic materials³. HGR regulations stipulate patient and genetic information cannot be exported from China, which includes electronic inspection of source data such as Test Request Forms and Subject Test Reports.
4. Numerous dialects exist for communication within China with Mandarin being the most common. However, additional dialects may be used depending on geographic location such as Cantonese and Shanghainese. The top 20 pharmaceutical companies by revenue in 2022 are predominately based in the USA or Europe⁴, with a focus on the English language. These known language differences can hinder progress of Clinical Trials, and lead to verbal and written misunderstanding, errors and inefficiencies.
5. There are noted cultural differences between China and the USA or Europe which can impact efficient establishment and delivery of Clinical Trials. For example, USA and Europe predominately employ direct communication methods, whereby China favours indirect communication,⁵,⁶. Additionally, the importance of building personal relationships to aid business within China cannot be understated, which may contrast with approaches applied elsewhere in the USA and Europe for example⁷.
6. Commonplace challenges of Clinical Trial Monitoring…in China include completion of long-haul travel, visa and immigration clearance, use of currency and bank cards.

“Clinical Trial regulatory requirements are governed by the National Medical Products Administration (NMPA), which differ substantially from [other] global regulatory requirements.”

How has Almac Diagnostic Services overcome these challenges?

The Global Clinical Trial Monitoring Team at Almac Diagnostic Services has successfully overcome these challenges to enable effective and consistent monitoring of CTA and CDx programmes within China.

1. A dedicated Global Clinical Trial Monitoring Team – Almac Clinical Trial Monitoring Team routinely travel to our Chinese laboratory partners to facilitate onsite monitoring visits throughout the duration of the Clinical Trial. This enables full access to source data related to CTA and CDx and provides confidence in trial performance.
2. Knowledge of global regulatory regulations – The Almac Clinical Trial Monitoring Team have rigorous monitoring procedures in place which meet global regulatory guidelines, including the HGR regulation. They work closely with the Almac Diagnostic Services Regulatory Team to ensure applicable global regulatory regulations are continuously met and have proven adaptability depending on the Clinical Trial needs, risks and global location.
3. Strategic partnerships with several Chinese laboratory partners – Almac’s three Chinese lab partnerships enables us to conduct Chinese biomarker studies seamlessly on behalf of our sponsors. Our Chinese laboratory partners are CAP (College of American Pathologists) and ISO 15189 accredited. Additionally, our laboratory partners routinely undergo supplier and site qualification.
4. Native Language Speakers – Almac Diagnostic Services employ Global Clinical Trial Monitors whose native languages are Mandarin and Cantonese, they are also fluent in English and competent in several other Chinese dialects which benefits global biopharma partners working with Almac.
5. Open Lines of Communication & Issue Resolution – The Clinical Trial Monitoring Team adapt their monitoring, communication and management style for each Clinical Trial location. They have built strong personal relationships with Almac Diagnostic Services’ Chinese laboratory partners which enables open communication and resolution of issues.
6. Proven experience with day-to-day life in China – Our Clinical Trial Monitoring Team and Almac Travel Department is comprised of individuals who are highly experienced in global travel, completion of visa applications, clearing immigration requirements, and have proven experience with day-to-day life within China.

“The Almac Clinical Trial Monitoring Team have rigorous monitoring procedures in place which meet global regulatory guidelines, including the HGR regulation.”

Benefits of Working with Almac Diagnostic Services to Monitor CTA and CDx Devices in China

Almac Diagnostic Services Global Clinical Trial Monitoring Team are involved in China based CTA and CDx projects from prior to study initiation, all the way through to closeout to ensure consistency and effectiveness.

Almac Diagnostic Services has established strong trusting relationships with our Chinese Lab partners. We have built the framework and put in place robust processes to enable Almac to support Chinese biomarker studies on behalf of our sponsors. We can offer a ‘one-stop shop’ for your CTA and CDx Clinical Trials in China, removing the need for Biopharma clients to outsource the management of monitoring activities to other third-party vendors. Moreover, our robust monitoring procedures ensure client confidence in patient safety and data integrity throughout the entire Clinical Trial lifecycle.

The Clinical Trial Monitoring team are a dedicated internal team, employed by Almac, rather than being an outsourced function. The team report directly to Almac Diagnostic Services Global VP and Medical Director ensuring any critical findings are flagged immediately to Senior Management, enabling faster information sharing, decision making & resolution of issues that may arise.

References

1. https://www.mordorintelligence.com/ industry-reports/companion-diagnosticsmarket

2. ICH Guideline for Good Clinical Practice (GCP) E6(R2)

3. Regulations of the People’s Republic of China on the Management of Human Genetic Resources

4. https://www.fiercepharma.com/pharma/top- 20-pharma-companies-2022-revenue

5. https://catalyst.iabc.com/Articles/ understanding-cultural-differences-tocommunicate- in-a-global-world

6. https://www.watershedassociates.com/ learning-center-item/direct-communicationvs- indirect-communication.html

7. The benefits of “Guanxi”: The value of relationships in developing the Chinese market

Find out more

Almac can support your Genomic Services, Clinical Biomarker & CDx Development & Clinical Testing programs in China.

To find out more visit our website: China Region Diagnostic Services