All clinical trials must be conducted in accordance with ethical principles, strong scientific evidence, and clear and detailed protocols. The benefits of testing should outweigh the risks, and the rights, safety, and well-being of trial participants must be preserved by obtaining informed consent and maintaining confidentiality. Care must be provided by suitably qualified and experienced staff, and records must be easily accessible and retrievable for accurate presentation, verification, and interpretation. Research products must be manufactured in accordance with good manufacturing practices (GMP).
The European Medicines Agency (EMA) provides guidance in the form of questions and answers (Q&A) on good clinical practices (GCP), as discussed and agreed by the GCP Inspectors Working Group. In the case of liquid formulations, the packaged volume must be measured with adequate precision and accuracy. If a reconstitution of the product is necessary, follow the instructions included with the product. If a specific volume of liquid is to be used for reconstitution, this volume must also be measured with adequate precision and accuracy.
A standard operating procedure (SOP) must describe packaging operations step by step, including the controls to be performed at each step and the responsibilities of each person involved. These operations must only be carried out by authorized, qualified personnel through training and education. Access to IMPs must be limited to authorized personnel, both before and after packaging. Storage conditions must conform to the provisions of the protocol (temperature, humidity, protection from light, if applicable).
Copies of the labels must be attached to the batch records, showing that they have been compared to the random distribution list and approved. All checks carried out and the identity of the people carrying out each check must be documented with the signature of the person in charge. Labeling should ensure subject protection and traceability, allow product and test identification, and facilitate the proper use of the IMP. The use of words such as 'dispensing' or 'dispensing' is not recommended to refer to the delivery of a prepared dose of an identified medication to a subject in order to avoid possible misunderstandings or confusion. This operation is more appropriately defined as 'administration', which includes directly introducing medication into or onto an individual's body.
The process of administering IMPs to subjects must be described in an SOP. The number of IMP units administered to each subject must also be documented at the time of administration. Specialized subcontractors are increasingly being used to carry out sponsor-specific tasks such as monitoring, data management, interactive voice response systems (IVRS), management of electronic patient journals or CRFs, etc. In addition, there are contractors who perform tasks that are partially or fully related to investigator responsibilities even if they have their main contract with the sponsor and are remunerated by them (these tasks may include specialized tests, retention of source data (especially in the context of e-CRF or electronic patient diary) or recruitment or patient follow-up contacts). This fragmented distribution of tasks could put additional pressure on maintaining quality assurance and compliance while hiding clear lines of hierarchy and responsibility for these tasks. Therefore, great care must be taken to ensure that the distribution of tasks is clearly documented and agreed upon; that each party has control over and access to data and information required by their legal responsibilities; and that ethics committees and regulatory authorities that approve trials have been duly informed of these activities as part of clinical trial application process.
All tasks related to clinical trial are ultimately responsibility of sponsor or investigator. Great care must also be taken to ensure that relative distribution of tasks between different parties is well defined; making clear final responsibilities in context of each clinical trial. This should be carefully documented in protocol, procedures, contracts or agreements, and other documents. Specific characteristics of each particular clinical trial should also be taken into account when planning trials during their conduct and monitoring; as well as through audits or inspections. This is particularly important when establishing novel agreements that may arise; for example in case of site management organizations (SMO) or other organizations that perform tasks related to researcher responsibilities but where organization has its contract and funding with sponsor. These tasks can often involve contact with study subjects; personal data such as identity or contact information should not be communicated outside parties that have received approval from ethics committee; nor should it be used or communicated for purposes other than those agreed by ethics committee; consented to by study subjects; where appropriate their caregivers; or other people who can be contacted whose data can be kept. Source data are defined at International Conference on Harmonization Technical Requirements for Registration Pharmaceutical Products for Human Use (ICH) (GCP) (1,5) as all information from original records certified copies original records clinical findings observations other activities clinical trial necessary reconstruction evaluation trial.
Source data must accurate readable contemporary original attributable complete consistent. Purpose identifying location source data verifying source data considerable part work supervisors auditors inspectors. During GCP inspections often observed data recorded several places site; therefore essential possibility reconstructing clinical trial make clear original record documented. Identification list places source data documented primarily intended tool monitors auditors inspectors work verify test being carried accordance ICH GCP guidelines current legislation guidelines ethics committees regulatory authorities approve trials duly informed activities part clinical trial application process. All tasks related clinical trial ultimately responsibility sponsor investigator. Great care taken ensure relative distribution tasks between different parties well defined making clear final responsibilities context each clinical trial.
This carefully documented protocol procedures contracts agreements other documents specific characteristics each particular clinical trial taken account when planning trials during conduct monitoring through audits inspections. This particularly important when establishing novel agreements may arise example case site management organizations (SMO) organizations perform tasks related researcher responsibilities organization contract funding sponsor. These tasks often involve contact study subjects personal data identity contact information communicated outside parties received approval ethics committee used communicated purposes agreed ethics committee consented study subjects appropriate caregivers people contacted data kept.
