METHOD OPTIMIZATION ACCORDING TO

CURRENT REGULATION FOR LIQUID

CHROMATOGRAPHY
The Need for Modernization and How to Managing Post Approval Change of
Analytical Procedure for Successfull Registration Acceptance

Goal :
- Patient safety
- Technology advancement (UHPLC, Diode Array Detector for ID test)
- Sustainability (replace toxic solvent, reduce solvent consumption)

Company Initiative
Quality Aspect (Compendial Consideration)
Quality —> QTPP —>
Regulatory Aspect
Process design —> process qualification —> continued process verification
Bussiness Aspect
High quality results, less cycle time, lower cost

Changing Landscape
Challenge for industry
- Higher results (increasing demand for testing)
- Better results (right first time)
Enabler
- Mature technology
- Regulatory harmonization

Case 1 : Compendial Method with FI VI/USP Chromatographic Adjustment  Verifikasi

Bisa diimplementasikan dahulu lalu diregistrasikan

Case 2 : New Alternative Method  Validasi

Harus diregistrasikan terlebih dahulu untuk bisa diimplementasikan
Method Farmakope harus dijalankan terlebih dahulu
Method bisa mengacu dari Pharmacopoeia Forum
Syarat : harus setara atau lebih baik dari Farmakope (productivity, efficiency, cost,
quality (accuracy, precision))  misal tidak memakai larutan toksik, dll

Empower analytics 3.7  ada fitur untuk mengkonversi dari hplc ke uplc

Understanding the Benefits and How to Modernize USP Monographs

The Change in USP <621>
- Harmonizing specifically with the current EP and JP
- Overall changes :
 Uses peak width at half-height to calculate resolution

Now the monograph clearly tell that signal to noise has to calculate the blank injection
S/N aceeptance criteria EP 20, USP 5

Hazards of Older Technology

- Older column technology is still on the market (Bondapak/Xterra)
More likely to have batch to batch variability due to older manufacturing process
- Older instrumentation

Benefits of Modernization

Achieve First Time Quality and Increase Laboratory Productivity with Waters
NextGen LC System

Application Updates : Sucralose Analysis Following USP Compendial

Detector : RID, Electron Light Scattering (ELSD), Single Mass Spechtrophotometer
(QDA)

RID
Untuk bahan yang tidak memiliki gugus kromofor & tidak memiliki serapan UV (ex.
alcohol, sugar, saccharides, fatty acids, polymers)
When a beam of light passes from one medium into another, it changes its speed
If the light enters a second medium at an angle that is not perpendicular to the medium’s
surface, the light is bent (refracted)
Yang dihitung merupakan pergeseran sudut biasnya
Tidak bisa gradient karena reference standard hanya disetting initial mobile phase, jika
dibuat gradient tidak akan dapat hasil

ELSD
Fase gerak : Nitrogen – ACN (lebih baik jika banyak organik agar mudah menguap,
hingga tersisa sampel)
Bentuk : droplet
Untuk pengujian sugar, antibiotic, antiviral, lipid, phospholipid, biomolecule, natural
product
Bisa gradient karena tidak di set reference standard

Plate count : berpengaruh dari RT dan Peak Width