With the expansion of clinical research and development, precise labeling of investigational products is not merely a formality but a critical aspect ensuring the safety, efficacy, and regulatory compliance of clinical trials. Pharmaceutical companies are obliged to follow an integrated approach in labeling considering all aspects of clinical study planning to promote multilingual and multicultural inclusion.
According to the Code of Federal Regulations (CFR), an Investigational Medicinal Product (IMP) is “any new drug or biological product that is used in a clinical investigation”. Investigational products do not have a stringent regulatory framework for labeling, packaging etc. (unlike those for marketed & commercially available products). As a result, the lack of specific guidance and robust regulations leaves gaps for troubling issues concerning product safety at clinical testing sites and violation of participants’ rights.
Clinical supplies require proper labeling to communicate important information to stakeholders involved in clinical trials & investigations. This includes instructions for use and administration details, product strength and dosage form, storage conditions and expiry dates. Each label should be patient specific rather than trial specific and likely to differ between countries involved. The placebo labels for blinded trials must resemble those of the active products but be discernible by the sponsor by virtue of unique identifiers.
Auxiliary Medicinal Products (AMPs) in clinical studies are just as crucial as IMPs. AMPs, which are also referred to as Non-Investigational Medicinal Products (NIMPs), comprise drugs given to study patients for various purposes such as supportive, rescue, preventive, diagnostic or therapeutic treatment while at the same time conducting trials. Although AMPs typically have marketing authorization in the country of research, there could be a need for approvals in some jurisdictions where authorization is pending.
Purpose of Regulatory Labeling Requirements
In clinical trials, regulatory labeling requirements are key to protecting subjects. This is to impart clear information about the investigational medicinal product being used in the study. Both researchers and participants need this identification so that they are informed about substances administrated during treatment. Regulatory labeling helps in tracking IMP throughout the entire trial process, which allows for systematic monitoring and accountability.
Moreover, proper labeling aids in identifying the trial itself by distinguishing it from other studies, hence ensuring accurate data collection on its part. Lastly, regulatory labeling guidelines ensure proper documentation of the trial process thus maintaining transparency, integrity, and compliance with regulatory standards.
Standard Requirements for clinical labeling:
- Clear Identification of the drug
- Dosage Information
- Batch Traceability
- Clinical Trial Reference
- Expiration Date
- Storage Conditions
- Safety Warnings
- Incorporation of Symbols for clarity
With the evolution of regulatory frameworks, European Union (EU) Clinical Trial Regulation (CTR) issued an application “Labelling of investigational medicinal products and auxiliary medicinal products” mentioning the substitution of New Annex VI in place of currently applicable Annex 13 brings about significant changes in the labeling requirements for investigational products. This updated annex provides comprehensive guidelines tailored to modern clinical research practices, highlighting:
- Enhanced Clarity and Consistency
- Integration of Technology
- Harmonization with International Standards
- Focus on Patient-Centric Approach
The newly applied Annex VI outlines comprehensive guidelines for labeling pharmaceutical products involved in clinical trials. It mandates specific information to be included on both immediate and outer packaging, such as contact details, substance details, clinical trial references, and storage instructions. Additionally, it requires the inclusion of a cautionary statement indicating investigational use only. For products provided with outer packaging, essential details may be limited to the immediate packaging. Special provisions are made for small packaging like blister packs, and unauthorized auxiliary medicinal products are strictly regulated.
Furthermore, safety concerns regarding labeling in clinical trials are addressed, including issues like name overlapping, absence of generic names, incorrect expiry dates, and misinformation on quantities. These regulations aim to ensure the safe and transparent conduct of clinical trials and the protection of participants’ well-being.
Conclusion
Regulatory labeling requirements serve many purposes including protecting participants’ rights, ensuring accurate data gathering while upholding ethical issues in clinical research.
In essence, meticulous planning and adherence to regulatory standards are obligatory for the effective labeling of clinical supplies and investigational products, ensuring patient safety, data integrity, and regulatory compliance across diverse global contexts.
DDReg provides end-to-end Pharmaceutical Product Labeling services and safety solutions for a range of pharmaceutical products. Reach out to the experts for more information. Read more about labeling here: Supporting Labeling Compliance with Searchable Databases.
Want to read more? Find the links below:
- 21 CFR Chapter I, Subchapter C, Part 211, Subpart G: Packaging and Labeling Control
- US FDA: Clinical Studies Section of Labeling for Human Prescription Drug and Biological Products- Content and Format
- US FDA: Quality System Regulation Labeling Requirements
- EMA: EU GMP Requirements for Investigational Medicinal Products
- Regulation (EU) No 536/2014 of the European Parliament: Labelling of Investigational Medicinal Products and Auxiliary Medicinal Products.
- EudraLex: EU Guidelines to GMP Medicinal Products for Human an Veterinary Use- Investigational Medicinal Products