This document, published by the European Medicines Agency (EMA) in 2015, provides comprehensive regulatory guidance for the pharmaceutical industry and national competent authorities on minimizing and preventing medication errors throughout a medicinal product’s life-cycle.
1. Introduction & Scope
- Definition: A medication error is an unintended failure in the drug treatment process (prescribing, storing, dispensing, preparation, administration) that leads to, or has the potential to lead to, harm.
- Problem Significance: Medication errors are a major public health burden, are largely preventable, and represent a significant cost.
- Scope: The guide focuses on errors arising from the medicinal product and its delivery system, including its name, design, dosage form, device, and packaging. It complements other EU guidelines on Good Pharmacovigilance Practices (GVP).
2. Key Principles & Process
- Proactive Life-cycle Approach: The potential for medication errors must be considered from early product development and continuously throughout the product’s life.
- Risk Management Cycle: This involves a continuous cycle of:
- Identify & Analyse: Identifying potential risks.
- Select & Plan: Planning risk minimization and characterization.
- Implement: Putting the planned measures into action.
- Evaluate & Collect Data: Monitoring effectiveness and collecting new data.
- Key Tools:
- Root Cause Analysis (RCA): To investigate the underlying causes of errors.
- Failure Mode and Effects Analysis (FMEA): A proactive method to identify what could go wrong, how, and why.
- Human Factors/Usability Engineering: Testing to ensure products and instructions can be used safely and effectively by the intended users.
3. Assessing Potential for Errors
- Product Design: Consider all aspects (e.g., tablet appearance, concentration of solutions, patch application) and how they might be misused.
- Clinical Trials: Errors can occur here due to plain packaging, small fonts, or complex packaging designs. Usability studies are recommended.
- Post-Authorisation: Real-world use often reveals new errors at various stages:
- Prescribing: Wrong drug, dose, or regimen.
- Dispensing: Selection of wrong product due to similar names or packaging.
- Preparation & Administration: Incorrect dilution, wrong route (e.g., IV vs. IM), or using expired products.
- Device-Related: Device failure or misuse.
4. Risk Minimisation Measures
This is the core of the guide, detailing how to reduce risks.
- Routine Measures:
- Naming: Avoid look-alike, sound-alike names. INNs and invented names are reviewed to prevent confusion.
- Packaging & Labelling: Ensure clear identification of the product, strength, and critical warnings. Use of colour should be careful and not the sole differentiator. Information must be accessible (e.g., Braille for the visually impaired).
- Product Information: The Summary of Product Characteristics (SmPC) and Package Leaflet (PIL) must be clear, comprehensive, and user-tested.
- Additional Measures: For higher risks, these can include:
- Educational materials for Healthcare Professionals (HCPs) and patients.
- Direct Healthcare Professional Communications (DHPCs).
- Training videos, demonstration kits, and controlled pack sizes.
- Specific High-Risk Groups:
- Paediatric Patients: High risk of dosing errors; need for weight-based calculations, appropriate formulations (e.g., liquids), and safe dosing devices.
- Elderly Patients: Challenges with swallowing, dexterity, vision, and polypharmacy; need for clear information and suitable packaging.
- Visually Impaired: Mandatory Braille on packaging and availability of accessible format leaflets.
5. Roles and Responsibilities (EU Regulatory Network)
- Marketing Authorisation Holders (MAHs): Responsible for operating a pharmacovigilance system, collecting error reports, updating Risk Management Plans (RMPs), and implementing risk minimization measures.
- National Competent Authorities (NCAs): Responsible for national pharmacovigilance systems, collecting reports, and taking regulatory action.
- EMA & PRAC: Responsible for assessing risks and the effectiveness of risk minimization measures for the EU, particularly for centrally authorized products.
- Patients & HCPs: Encouraged to report medication errors and are key targets for risk minimization communications.
6. Annexes (Practical Examples)
The guide includes valuable annexes with real-world examples:
- Annex 1: Lists potential sources of error for various product types (tablets, capsules, patches, inhalers, injections) and provides case studies of errors (e.g., name mix-ups, wrong dosing).
- Annex 2: Provides design features that can reduce the risk of errors (e.g., distinct tablet colours/shapes, clear instructions for patches, appropriate measuring devices for liquids).
- Annex 3: Gives examples of how Post-Authorisation Safety Studies (PASS) have been used to further characterize and manage medication errors.
In conclusion, this guide establishes a proactive, life-cycle approach to medication safety, emphasizing that careful consideration of a product’s name, design, and information is crucial to prevent errors and protect public health.
