Are you aware of the worldwide differences in regulations for global clinical trials?

Among other factors affecting global clinical trials, country-specific regulations differ in their rules and standards for:

• Gathering and protecting data
• Importing and exporting clinical supplies
• Handling validation issues
• Protecting human subjects
• Exercising quality control

Gathering and Protecting Data:

Global clinical trials are conducted in emerging countries such as Eastern Europe, Asia, and Latin America because highly trained medical personnel are willing to participate in clinical trials in these countries for economic and professional benefits, and their populations are more motivated to participate due to a lack of comparable medical care and follow-up. Furthermore, overall costs are lower in emerging countries.

Country-specific regulations vary in their rules and standards for gathering and protecting data, importing and exporting clinical supplies, handling validation issues, protecting human subjects, and exercising quality control. 

Among other important steps, the Sponsor or CRO should: 

• Train every participating medical professional in standard operating procedures.
• Decide on the best mechanisms for gathering and protecting data based on the actual site and study participants rather than on “ideal” conditions.
• Continuously monitor the benefits and risks to the study population during the clinical trial.
• Continuously monitor medical and laboratory facilities to make sure they are ready for outside inspection and that data are protected.
• Make sure all notifications to regulatory authorities are made in a timely manner, such as registration of the trial, reports of adverse reactions, and notification of the end of a trial.
• Watch out for signs of possibly compromised data, such as under-reporting of adverse reactions or high turnover/extremely fast enrollment of study participants.

Handling Validation Issues

When it comes to validating the medical qualifications of medical staff who are participating in a clinical study, Sponsors and CROs enter an area that may not be clearly defined by regulations. However, it has serious ramifications.

Several factors may enter into a determination of medical qualifications: educational facilities in the country may be limited, especially research and laboratory facilities; credentials that are acceptable in one country may not be acceptable in another; and a different set of cultural norms may influence medical decisions and reporting. 

Among other important steps, the Sponsor or CRO should:

• Know what various regulatory agencies consider an acceptable level of professional qualifications for medical professionals in a clinical research study.
• Interview the medical staff before they participate in the study to measure their qualifications as well as their ability to communicate with the Sponsor, CRO, each other, and the study participants.
• Train all medical personnel in standard operating procedures (SOP) to ensure a common level of skill.
• Observe how medical personnel use medical and laboratory devices that are not common in the site country; train personnel to make sure the devices are being used and maintained properly.
• Keep track of agencies and organizations (such as the General Medical Council in the United Kingdom) that evaluate overseas institutions to determine if they have acceptable medical training programs.

Other medical-related validation issues may crop up during the clinical trials. For example, data must be validated. Medical professionals in the study need to be able to write legibly and need to use the same medical coding. When multiple languages are involved, this requirement may become a more difficult problem.

Human factors have to be validated. The study participants need to understand and be able to follow through on instructions and properly use any drugs or devices given to them. For example, the study participants may not have access to the resources needed to clean devices, safely store drugs or return periodically for evaluation.

There is great importance in validating the medical qualifications of medical staff, understanding the country’s definition of controlled substances, and knowing the regulations surrounding the import and export of clinical supplies. It is crucial to balance the benefits of conducting global clinical trials with potential problems that could arise if sponsors or CROs are not aware of country-specific regulations or inadvertently violate them.

Importing and Exporting Clinical Supplies

Every batch of clinical supplies must be certified as conforming to good manufacturing practice and quality control, satisfying regulations at the site country, the country of origin and, after the study is completed, the country where supplies will end up. Products must be labeled according to each country’s regulations.

Among other important steps, the Sponsor or CRO should:

• Establish relationships with local professionals who are experienced with and qualified to interact with import and export agencies in the site country.
• Understand the country’s definition of controlled substances, including drugs needed for pain relief, and the effect of prohibitions on the study participants.
• Know the regulations surrounding the import, disposal and export of biological samples and of clinical supplies.
• Protect clinical supplies against theft or misuse, especially in politically unstable countries.

Human Subject Protection

Every country and every ethical Sponsor and CRO should be concerned that clinical trials provide benefits to the study participants that outweigh the risks.

Among other important steps, the Sponsor or CRO should:

• If applicable, make sure that the country allows phase 1 studies.
• Make sure that interactions between medical staff and study participants are consistent with international guidelines (such as Council for International Organizations of Medical Science (CIOMS), the International Conference on Harmonisation (ICH), the Declarations of Helsinki, and the US Belmont Report.
• Make sure that study participants are not exposed to unnecessary risk.
• Arrange for an independent ethics board review.

Quality Control

Quality control covers good medical, clinical and licensing practices.

Because of the efforts of the International Conference on Harmonisation and other organizations, standards of good clinical practice (GCP), good manufacturing practice (GMP), and good licensing practice (GLP) have become more uniform from country to country. The benefits to Sponsoring organizations are enormous.

For example, responsibilities and expectations are more clearly understood from country to country. Clinical data gathered in one country can now be used to file new drug applications in another country. Compliance with regard to documentation, study protocols, investigator qualifications and patient protection is more feasible and economical because there are fewer nonconforming regulations.

However, Sponsors and CROs should never take quality control for granted.

Among other important steps, the Sponsor or CRO should:

• Build quality into the planning stages, with risk-based quality management.
• Understand the country’s method and criteria for issuing GMP certifications.
• Inspect manufacturing, warehousing and distribution locations.
• Align with trusted local representatives who can help ensure compliance with GMP and other quality regulations.

In risk-based quality management, the Sponsor or CRO concentrates resources on reducing risks to GCP, GMP, and GLP where they are most likely to occur. This targeted approach increases quality because the Sponsor or CRO anticipates problems.

Where Confidence Pharmaceutical Research Fits In:

Our global experience in clinical trials has enabled Confidence Pharmaceutical Research to keep up with regulations throughout the world. We have local specialists who can help you guide clinical trials safely through myriad regulatory, cultural, professional, ethical and procedural challenges.

Our ability to navigate and evaluate the effect of country-specific regulations makes Confidence Pharmaceutical Research one of the world’s leading contract research organizations. 

For more information about our methods and capabilities, please contact us today.