I have reviewed 50+ cleaning validation protocols this year.
And here is what still surprises me: Most companies treat FDA and EMA requirements as identical twins.
They are not.
The reality is:
Last year, a client passed their FDA pre-approval inspection comfortably. Same facility. Same equipment. Same cleaning procedures.
Three months later, EMA flagged critical gaps during their GMP audit.
The culprit is subtle but significant DIFFERENCES in how each agency defines “ADEQUATE” cleaning validation.
Let me break down.
The FDA wants Proof of Removal:
21 CFR Part 211.67 is straightforward: Prevent contamination. They focus on what you remove (API residues, cleaning agents, bioburden) and how much is acceptable.
They want to see:
- Worst-case scenarios identified through risk assessment
- Visual inspection as the first line of defense (yes, really)
- Strategies that make scientific sense
- Consecutive successful cleaning cycles (the golden rule)
For a multi-product facility mfg. antibiotics and steroids, the FDA expects you to validate cleaning after the “dirtiest” product (highest dose, lowest solubility, highest toxicity). Prove that works.
The EMA demands Proof of Control:
EudraLex Volume 4, Annex 15 takes it further. They are not just asking “did you clean it?” They want to know: “Can you prove your cleaning process is consistently under control?”
Their focus:
- Lifecycle approach to cleaning validation
- Ongoing verification through routine monitoring
- Matrix approach with clear scientific rationale
- Risk assessment that considers patient safety and product quality equally
For the same facility above. EMA wants your continued process verification (CPV) program documented.
They will ask: “What is your ongoing monitoring frequency? How do you trend results? When was your last cleaning validation requalification?”
IMP: Cleaning Validation is about protecting patients from one thing they should never worry about: What was made in that equipment before their medicine.
On top of their respective requirements and to satisfy both regulations (which are globally recognized), build in:
- Risk-based worst-case selection
- Health-based and quality-based limits
- Visual + analytical verification
- Ongoing monitoring with trending
- Periodic revalidation triggers
Because this is where they align closely. My advice after 12 years in validation:
- Don’t chase Compliance. Chase consistency.
- If you design your cleaning validation program to meet the stricter requirements, you become Compliant.
Thoughts should flows like top-down approach:
Compliance ➔ Consistency ➔ Discipline ➔ Habit ➔ Clarity ➔ Intent ➔ Purpose.
What has been your biggest challenge with cleaning validation? Drop a comment.
Read also: Bracketing and Worst Case Rating in Cleaning Validation
Resource Person: Saket Yeotikar