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Eun-Sook Gi
April 12, 2004
㈜ 삼양제넥스 생명공학 연구
소
Regulatory and Requirements
FDA, July 1993
Guide to inspection for validation of cleaning
process
Application
regulation and requirements:
21CFR 211.65, 21CFR 211.67
언제 Cleaning validation 실시 ?
New equipment/product
Changed : 생산 process, cleaning process, 세척제
Changed : major component
Cleaning validation Overview
Good system design
Master validation plan
Preliminary study
- Coupon study
- Cycle Development study
- Continuous data monitoring
- Justifiable acceptance criteria
Effective cleaning process development
Adequate analytical technique
Master Validation Plan
Appropriate cleaning procedure
Identification of cleaning agent
Description of sampling procedure
Acceptance criteria
Analytical method
A copy of protocol and final report
A list of equipment
Manufacturing process( a flow diagram)
Master Validation Plan
CIP or COP
Equipment matrix for CV
Description of equipment and its location
Surface area of equipment
Average batch size of each equipment
Training program for production and analytical personnel
Reference to the company’s change control program
Sampling Procedure
Sampling SOP
Rinse or swab(surface) sampling
Rinse sampling: volume, valve define
Swab sampling: map of each equipment
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Product/Cleaning Agent 관계
Molecular structure (Bio product or small
molecule)
Prod related compound
Solubility: in water or in org. solvent?
Reactivity
Contaminant: Fluid or Solid?
Cleaning agent selection
Coupon Study
Coupon: Equipment 와 동일 surface type SUS or
Glass (5 x 5 cm, 10 x10 cm)
Swab: polyester
Characterization of residue
Worst case of cleaning condition
Selection of cleaner visually clean
Cleaning condition 설정 : temp. range, cleaning
agent conc., pressure(agitation, shaking), rinse
volume visual inspection
Swab Test / Swab Recovery
Swab method: sample, control and blank test
P01
Equipment System Design
Consideration of CIP system for effective
cleaning
Piping size 와 구조 (slope)
Potential dead leg
Turbulence of CIP solution
Nozzle design: locate seal near vessel wall
Branch piping
Instrument Tees
Instrument Tee for CIP: L/D <1.5
L D
Vertical up
Bad design
Vertical down