Ensuring the safety and efficacy of pharmaceutical products requires meticulous attention to cleaning validation. When introducing a new product to a facility, understanding and implementing HBELs is crucial.
This blog will explore the key considerations and best practices in determining HBELs, highlighting insights from our new training course, Cleaning Validation Best Practices in Pharmaceuticals.
Key Considerations for Determining HBELs
- Quality Risk Management and Change Control: Every new product introduction must undergo a thorough review through Quality Risk Management and change control processes. Assess whether existing technical and organisational controls are adequate or need modifications.
- Evaluating HBEL Suitability: Assess the HBEL of the new product for compatibility with your facility. Determine if dedicated facilities or additional checks are required to manage the new product safely.
- Ease of Cleaning: Evaluate the cleanability of the equipment used for the new product. Regardless of whether the new product represents a worst-case scenario, determine if current cleaning processes are sufficient or if new or revised processes are necessary.
- Impact of New Equipment: Consider any new equipment or changes that might affect cleanability. Ensure that these changes are factored into the cleaning validation process.
Determining Maximum Safe Handling Limits
The maximum safe handling limit is the permissible residue level in equipment after cleaning. This is calculated to ensure that the API from the first product does not exceed the HBEL when transferred to the second product. This involves:
- Risk Management Principles: Use risk management to determine maximum allowable residue removal. Limits should be based on toxicological evaluations documented in a risk assessment.
- Warning Limits: Establish warning limits if HBEL-derived cleanliness limits are significantly higher than historical ones. Cleaning procedures should achieve better limits than those derived from HBELs, meeting visually clean criteria.
- Analytical Methods: Ensure that analytical methods can detect residues at acceptable levels below these limits. If necessary, improve analytical methods or consider alternative risk reduction methods such as dedicated equipment.
- Cumulative Impact: Establish acceptance criteria that account for the cumulative impact of residues from multiple shared equipment.
- Periodic Re-evaluation: Periodically re-evaluate HBELs and document the impact of any changes on the overall cleaning validation programme.
Analytical Procedures for Cleaning Validation
Effective cleaning validation relies on robust analytical procedure. Key points include:
- Validated Procedures: Samples should be analysed using validated procedure developed according to Analytical Quality by Design principles.
- Specific Methods: Utilise High Performance Liquid Chromatography (HPLC) and other specific methods where appropriate. Non-specific methods like UV spectrophotometry should only be used if specific methods are not feasible, justified by risk assessment results.
- Scope of Validation: Define and justify the scope of validation when transferring analytical procedures from research and development to facility laboratories. Procedures must detect residue levels at the maximum safe surface residue level.
By understanding and applying these best practices in determining HBELs, you can ensure the safety and compliance of your pharmaceutical manufacturing processes.
For a deeper dive into these topics and more, join our upcoming training course, Cleaning Validation Best Practices in Pharmaceuticals. Learn from an industry expert and enhance your knowledge to maintain high standards in your facility.
Published on Aug 19, 2024 by Jasmin Cheklam-Smith