The current change criteria for USP <621> (Chromatography) were significantly updated in December 2022 to allow greater flexibility in method adjustments while maintaining system suitability. Here's a summary of the key allowable changes we found using Copilot.:

✅ Allowed Adjustments Without Revalidation (if System Suitability Passes with changes)

Column Parameters

• Column Length & Particle Size:

  • You may adjust the column length and/or particle size as long as the L/dp ratio (length/particle size) remains within −25% to +50% of the original.

• Internal Diameter:

  • Can be changed even without altering particle size or length.

Mobile Phase Composition

• Minor components can be adjusted by ±30% relative, but no component should change more than ±10% absolute.

pH and Buffer

• pH: ±0.2 units (unless otherwise specified).
• Buffer concentration: ±10%.

Injection Volume

• Can be adjusted using a specific formula to maintain proportionality with other method parameters.

Column Temperature

• Isocratic methods: ±10°C
• Gradient methods: ±5°C

Gradient Methods

• Previously not allowed, gradient adjustments are now permitted, provided system suitability and selectivity are maintained.

Detector Wavelength

• No changes allowed.

🧪 System Suitability Requirements Must Still Be Met

Even with these adjustments, the method must still meet system suitability criteria such as:

• Resolution
• Tailing factor
• RSD of replicate injections
• Selectivity and elution order of impurities
• Signal to Noise remains within guidelines

📚 References

• USP Official Harmonization Notice[2]
• Modernization Guidelines with SPP Columns[3]