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Controlled Substances in EU Clinical Trials

Controlled Substances in EU Clinical Trials

Key Considerations for Biotech and Pharma Working with Controlled Substances

Clinical trials involving controlled substances significantly increase complexity in trial design, execution, and more. However, given the promising potential of these treatments, does not deter the investigation of these substances in central nervous system (CNS) indications.

Running these trials successfully requires a true understanding of the laws and regulations surrounding this category of drugs across Europe. In this article, we will outline key considerations sponsors looking to run controlled substances clinical trials in the European Union (EU).

EU Controlled substance clinical trials are on the rise

The number of these trials has been rising steadily with a notable increase in new trials over the past two years, according to data pulled from Citeline’s Trialtrove® (AUG 2023).

Note: This is a paid platform that requires a subscription and the data displayed is dynamic, changing in real time.

Figure 1. Growth in the number of CNS clinical trials involving controlled substances within the EU.

The rapid growth is fueled by rising research interest in CNS and Europe’s openness to studying controlled substances.

Controlled substance research spans several CNS indications

The development of drugs that interact with receptors in the brain and alter consciousness offer the potential for promising therapeutic benefits across a range of psychiatric, neurological, pain disorders.

Disease_20230726144554Figure 2. Breakdown of CNS indications being investigated for controlled substance therapy in EU countries.

Europe is an attractive destination for these studies due to diverse patients, expertise, and infrastructure that can support in the investigation of the safety and efficacy of these substance for therapeutic application.

Overview of EU Regulations for Controlled Substances

Each European country categorizes controlled substances differently based on international drug conventions. The level of control depends on the substance’s potential for harm or abuse—high-risk drugs face stricter regulations than lower-risk ones.

While the EU Clinical Trials Regulation (EU-CTR) harmonizes processes for clinical trials across Europe, controlled substance protocols still require individual country approvals. Extra steps are still needed for handling, administration, and oversight compared to other investigational drugs.

These measures aim to prevent diversion and ensure proper use, but they also create logistical complexities versus standard clinical trials. Companies must budget more time and resources when working with controlled substances.

Regulation Differences Across European Countries

Under the EU-CTR, some differences in definitions and procedures for controlled substances have been unified across Europe. For example, rules for importing, storing, and transporting these drugs are now standardized. However, some country-specific nuances remain around aspects like license applications, dose preparation, documentation, and destruction requirements.

While the changes resulting from the EU-CTR have helped to streamline certain requirements, there still exists the need to navigate individual country variations and nuances. Sponsors should look to verify the current laws in each target country when planning a study.

  • Managing DEA-Controlled Substances

    5 Considerations for Managing DEA-Controlled Substances in CNS Clinical Trials



The start-up phase is critical when investigating controlled substances

Due to the added oversight and restrictions around controlled substances, the start-up phase requires extra attention compared to standard clinical trials. Sponsors must identify and mitigate risks early to prevent delays.

Key start-up tasks include:

  • Thoroughly assessing regulations and import/export laws when selecting trial countries. this impacts timelines.
  • Developing distribution procedures adhering to each country’s security and documentation rules for controlled substances.
  • Evaluating if qualified pharmacies are available to securely manage drug supply and reconciliation.
  • Verifying sites have proper facilities and resources to store and administer controlled drugs.
  • Training staff on administration, inventory, reconciliation, and other protocols.
  • Implementing supervision and auditing practices to identify issues quickly.

Robust planning and strong oversight foundations during start-up are essential to comply with laws and run studies smoothly.

Best practices for controlled substance trials

To avoid issues with controlled substance trials, sponsors should look to incorporate these best practice strategies into the planning:

  • Assess regulations and import/export requirements before selecting trial countries and sites, as this impacts timelines.
  • Develop specialized distribution procedures adhering to each country’s security and documentation rules.
  • Use experienced pharmacies for supply management.
  • Have protocols reviewed well in advance by authorities and ethics committees.
  • Train site staff on proper handling, administration, inventory, and reconciliation procedures.
  • Implement robust supervision and auditing practices to identify any deviations quickly.

Following these steps will help to minimize risk and avoid delays when working with this class of drugs.

Mitigating risk during controlled substance trials

Preventing controlled drug diversion or misconduct is critical from a liability standpoint. Our recommended risk mitigation strategies include:

  • Background screening for staff handling the drugs.
  • Restricted access to controlled substances.
  • Detailed inventory logs and reconciliation processes.
  • Random audits of drug storage locations.
  • Secure transfer containers and tamper-evident seals.
  • Video surveillance and alarms where substances are kept.
  • Prompt drug destruction after trials.

Proper vigilance and protocols are the pillars of risk management in studies with scheduled drugs.

Looking ahead

As the field of CNS research using controlled substances expands, the EU Clinical Trials Regulation will continue unifying processes, though some country-specific nuances are likely to remain. By staying current on evolving regulations and partnering with an experienced CRO, sponsors can navigate these requirements confidently.

Challenges will always exist, but the right expertise and preparation can allow controlled substance trials to realize the potential for good these treatments can offer patients impacted by CNS.

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