Investigational Medicinal Product (IMP) Handling in Clinical Trials: Insights from Nepal

National Guideline On Clinical Trials With The Use Of Pharmaceutical Products , published by National Health Research Council (NHRC) defines Investigational Medicinal Product (IMP/IP) as any pharmaceutical form of an active ingredient or placebo undergoing testing in a clinical trial.

 Handling of IMP (Investigational Medicinal Product) involves a set of procedures including storage, dispensing, accountability, and documentation that ensures its safety, efficacy and acceptability profile.

Preparatory stage:

Before commencing a clinical trial, thorough pre-clinical studies are crucial to establish the potential safety and clinical applications of a pharmaceutical product. Manufacturing procedures and product tests should be conducted to confirm its suitability for investigational use. Data alignment with the trial phase and a concise compilation of safety and efficacy information from previous trials are vital prerequisites.

 It is crucial to provide detailed description and rationale for the route of administration, dosage, dosage interval, and treatment period for investigational and comparator products, incorporating considerations of dose-response relationships beforehand.

In Nepal, any IMPs must be scientifically verified for clinical trials, collectively by Nepal Health Research Council and Department of Drug Administration (DDA).

Supply and Storage:

The protocol should outline sponsor arrangements for supplying investigational products, specifying recording, delivery, dispensing, and storage procedures in accordance with Good Manufacturing Practice. The sponsor is responsible for the trial drug’s supply and quality, with the possibility of regulatory authority’s cooperation for import or manufacturing. Investigators manage drug records, including quantity, manufacturer details, and control samples, ensuring adequate stock at trial sites.

 The Chief Investigator, in collaboration with the pharmaceutical company and the host organization’s pharmacy department, must establish storage temperatures, conditions, times, reconstitution procedures, and infusion devices for Investigational Medicinal Products (IMPs) in the trial.

Temperature monitoring and quarantine procedures

The research team, or a designated team, is responsible for daily temperature monitoring, recording the current, maximum, and minimum temperatures using the specified form. The clinical trials team provides temperature loggers, conducts monthly visits, and addresses temperature excursions per SOP, quarantining affected IMPs until approved for use or replacement. Any necessary drug shipment is arranged promptly.

Investigational Labelling and Packaging

Sponsors are responsible for proper packaging and labelling of investigational products, ensuring compliance with protocols and regulations. Labels must convey the product’s clinical research purpose, use a coding system for blinded trials, and ensure indistinguishability among study and comparator products in appearance and characteristics. Blinded trial packages must use a coding system to conceal product identity, allowing proper identification in emergencies, and all study products should be indistinguishable in appearance, taste, smell, weight, and other physical characteristics.

Responsibility of a Investigator:

The investigator is responsible for safely handling investigational and comparator products, adhering to the protocol. This includes ensuring correct usage by designated staff, documenting usage for appropriate dosage, confirming understanding by subjects, and returning unused products as per the protocol, with meticulous record-keeping.

Responsibility of a Sponsor and Monitor:

The sponsor must supply investigational and comparator products following Good Manufacturing Practice, ensuring proper characterization, coding, packaging, and labelling. They should provide adequately sized packages, retain batch samples for control tests, and communicate expiry date information comprehensively. Monitors, during site visits, verify protocol adherence, proper inventory records, expiry date compliance, suitable storage conditions, and procedures for returned or unused study products.

Drug accountability

For precise drug accountability in the trial, record identifiers (Trial Name, EudraCT number, PI Name, Institution, IMP name), subject ID, dispense date, visit number, dose, kit number, dispensed quantity, batch number, expiry, return date (if applicable), returned quantity, and recorder’s initials. These details ensure accurate and transparent drug management.

Prescribing, dispensing and checking of IMP

After patient enrolment, a qualified prescriber, trained on the study and listed in the delegation log, prescribes the Investigational Medicinal Product (IMP). Various prescriptions, including trial-specific and electronic, may be used. The SOP outlines accurate dispensing and checking procedures, specifying tasks, prescription details, IMP dispensing, and accountability records. Only trained, delegated research team members can dispense and check the IMP, with adaptation based on study needs and Trust guidance.

Documentation and SOPs

The study-specific SOP provides detailed instructions on how to accurately dispense and check IMP, tailored to the specific requirements of the trial. This includes prescription completion, dispensing procedures, labeling, and adherence to accountability records.