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Before Initiation

Investigational medicinal products (IMPs) are pharmaceutical forms that are tested in a clinical trial for human use. These pharmaceutical forms include pharmaceuticals licensed or not licensed, which are applied to another (currently not licensed) indication or administration form, as well as placebos.

The sponsor-investigator has to ensure that the study site and the participant(s) are provided with enough IMPs. It is very important that the IMPs’ manufacturing and handling conform to the local laws.

Regulatory Reference

! EU Guidelines to Good Manufacturing Practice (GMP) Annex 13 Investigational Medicinal Products

! EU Directive 2001/20/EC, Art. 2, Art. 13, Art. 14, Art. 15

Responsibilities

Obtaining IMPs

After the study design and the corresponding IMPs are specified, how the IMPs are obtained has to be ascertained:

• Who delivers the IMP?

• What is the delivery status?

• What specific labelling requirements are defined/required?

• Is a manufacturer allowance needed?

Obtaining from a Manufacturer

If the IMPs were obtained from the original manufacturer, the following items have to be obtained and/or written down in detail:

• Relinquishing the IMP dossier

• Labelling

• Expiration date

• Amount

• Delivery conditions

Obtaining from a Pharmacy

If the IMPs were obtained from a pharmacy, the following aspects have to be written down in detail:

• Amount

• Availability

• Requirement to label

• Pharmacy fee (if any)

Labelling of IMPs

The labelling has to protect the participant, secure the traceability and identification and prevent the invalid usage of the pharmaceutical.

The following items have to be written on the label:

• Name, address and telephone number of the contact person

• Representative or code number to identify the substance

• Route of administration, dosage form, dosage units and, in the case of open trials, the name and the strength of the pharmaceutical

• Study number to identify the study, the sponsor-investigator and the study site

• Participant number

• Application advice

• Hint: use ‘Only for Use in Clinical Trial’ or similar wording

• Storage conditions

• Expiration date in format mm/yy

• If the IMP is used at the participant’s home: ‘Store away from children’

Under certain circumstances, items may be placed on a patient card.

Investigational Medicinal Product Dossier

The IMP dossier (IMPD, usually provided by the manufacturing company) contains all the relevant information or a reference to documents, which describe the detailed instructions regarding manufacturing, packaging, shipping and quality control. It must include:

(a) Documents about quality and manufacturing

(b) Import license

(d) Manufacturer allowance

(e) Scheduled labelling

(f) Summarized risk-benefit analyses

(g) Documents of results about clinical trials implemented so far

see 1

Risk-Benefit Analysis

Advice - Hints and Tips

Use symbols and graphics for clarification, as well as other standard warning notices and extra declarations. If the points (b), (f) and (g) from the IMPD are already provided in the IB, the sponsor-investigator can make a reference to the relevant sections there. Pay attention to the latest version of the IMPD appropriate to the development of the product.

During Study

During the clinical trial, the sponsor-investigator has the responsibility for the maintenance of the IMPs. These responsibilities include the reordering and checking of the IMPs to ensure a smooth execution until the end of the study. Additionally, the sponsor-investigator is required to document drug accountability.

Regulatory Reference

! EU Guidelines to GMP Annex 13 Investigational Medicinal Products

! EU Directive 2001/20/EC, Art. 2, Art. 13, Art. 14, Art. 15

Responsibilities

Recalls/Reclamations

Reclamations about the IMPs’ quality have to be documented and should be sent to the pharmaceutical manufacturer.

In the case of recalls, it is necessary to coordinate between the sponsor-investigator and the manufacturer. The sponsor-investigator and monitor must be clear about their duties.

Drug Accountability

Drug accountability is the documentation of the:

• Received IMPs, including expiration date and lot number

• Administered amount of the IMP per participant

• Lost amount of the IMP per participant (if any)

Dispensing and redemption of the IMPs is documented in the Drug Accountability Log. It should include the following:

• Name of the sponsor-investigator

• Protocol number and title

• Name of the pharmaceutical

• Date

• Amount

• Manufacturer

• Dose, form and strength of the pharmaceutical

• Lot number

• Study site number

• Signature of the employee responsible for the action

Advice - Hints and Tips

The return or disposal of unused pharmaceuticals is an important responsibility, which must be documented carefully. If the IMP is only to be used by the participant, it is important to educate him/her about the appropriate dosage amount as requested by the study protocol.

In the case of ambulant therapies, it is crucial to document patient compliance.

Forms and Templates

Drug Accountability Log

After Study

After terminating or completing a clinical trial, there are several options to document the use of all IMPs. The sponsor-investigator has the responsibility for how to handle cases of destruction, returning the IMP or other possibilities. Furthermore, it has to be ensured that the completion of the drug accountability log is conducted accurately.

Regulatory Reference

! EU Guidelines to GMP Annex 13 Investigational Medicinal Products

! EU Directive 2001/20/EC, Art. 2, Art. 13, Art. 14, Art. 15

Responsibilities

Destruction

The sponsor-investigator is responsible for the IMP - in particular, for the destruction of unused pharmaceuticals.

The delivery use and destruction of IMPs must be written down in detail. The balance has to be made up for every audit period. All IMPs must be accounted.

The destruction of the IMPs has to be proved with a dated and signed document. Furthermore, it must contain:

• Lot-number

• Participant-number

• Destroyed amount or complying traceability

Drug Accountability

The monitor’s task at the end of the study is to compare the trial notes to the Drug Accountability Log. If it is necessary, the destruction or redemption of the IMPs has to be initiated by the monitor.

see 23

Monitoring

Returning

The returning of IMPs must be in compliance with procedures, which were agreed to beforehand. Returned pharmaceuticals should be discernible as such and stored separately.

Advice - Hints and Tips

To destroy IMPs, a written approval of the sponsor-investigator is required. Their destruction has to be traceable, such that all actions have to be written down, signed by authorized study staff and dated.

Forms and Templates

Drug Destruction Log

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