Analytical Methods for Cleaning Validation
Im Auftrag der ECA Academy

Analytical Methods for Cleaning Validation  Im Auftrag der ECA Academy

Heidelberg, Germany

Seminar Nr. 18087

 

Kosten

ECA-Member: EUR 1590,--
Non ECA Member: EUR 1790,--
EU/GMP Inspectorates: EUR 895,--
APIC Member Discount: EUR 1690,--

Alle Preise zzgl. MwSt.

Rückfragen unter:
Tel.: 06221 / 84 44 0 E-Mail: info@concept-heidelberg.de

Sprecher

Dr Raphael Bar, BR Consulting, Israel
Walid El Azab, STERIS Cooperation, Belgium

Zielsetzung

This course consists of two parts. The first part revolves around the development of suitable analytical methods. The characteristics of these methods (HPLC, HPTLC, TOC, conductometry, pH, total protein, visual inspection etc…) will be discussed in the light of their capability of detection and quantitation of residues. In particular, the advantages of the TOC method in accurately  detecting  and quantifying  low levels of  nonspecific residues (such as detergents, drug excipients and active ingredients)  which may not be determined by HPLC, will be highlighted. Prior to this, the concept of Maximal Carry Over (MAC)  limits according to PIC/S, FDA and WHO guides will be presented along with the new EMA approach based on toxicity thresholds. Finally, a pre-requisite requirement for a well-developed analytical procedure is an efficient  sampling recovery and therefore, the first part of the course will highlight the various techniques of sampling recovery.

The second part of the course will address a systematic validation of the analytical method for cleaning residues. Performance characteristics of the analytical method  (accuracy, precision, linearity, robustness, sensitivity and sampling recovery) will be systematically presented and discussed in parallel to practising with guided calculations of examples with Excel.

Hintergrund

Initiating a manufacturing of pharmaceutical in shared equipment requires demonstrating that no cross-contamination from previous product takes place.  Optimally, residues from previous manufactured product or API or residues from the cleaning agent itself should be absent or very low. The validation of any cleaning process relies heavily on the validity of the test results provided by the analytical procedure for cleaning residues.  However, here lies the challenge facing an analytical chemist: the need to develop and validate an analytical method that is sensitive enough to detect and reliably quantify well recovered trace amounts of chemicals and practical enough to rapidly deliver results. 

Zielgruppe

The addressees of the event are analytical chemists testing the residues, quality control personnel, quality assurance personnel, regulatory affairs professionals, GMP auditors and inspectors and validation personnel also involved in cleaning validation.  
 
The participants should bring a laptop with Excel and activated Analysis ToolPack module.

Programm

Introduction Cleaning Validation and Regulatory Requirements
  • Regulations (FDA, EU, PIC/S, APIC, WHO)
  • Cleaning process
  • Life cycle of  cleaning process from development to validation
Understanding the  Allowable Carryover (MAC)
  • Common MAC limits (PIC/S, FDA and WHO guides)
  • New approach of EMA guide (NOAEL and PDE)
  • Residues limits on swab and rinse samples  and in analytical samples
  • Formulas for calculating MAC
Cleaning Method Characteristics
  • Types of cleaning residues and their  identification
  • Analytical methods for cleaning residues: specific versus non-specific (HPLC, HPTLC, TOC, Conductometry, pH, total protein, visual inspection etc…
  • Methods for validation and for monitoring
  • Limit test versus quantitative test
  • Correlation between specific and non-specific methods
  • Methods for cleaning residues
Sampling Techniques of Cleaning Residues
  • Swab and Wipe Sampling
  • Requirements from Swab
  • Rinse Sampling   
  • Solvent Sampling
  • Placebo Sampling
  • Product Sampling
  • Visual examination of cleaned equipment
HPLC, TOC  and Conductivity methods for residues
  • HPLC procedure for residues
  • Procedure for Total Organic Carbon
  • Procedure for conductivity
  • Testing methods for cleaning agents
Roadmap of Dev and validation of Analytical Procedure of Cleaning Residues 
  • Cleanability studies
  • Development of an analytical method for residues
  • Requirements from a method ready for validation
  • Validation strategy of analytical methods for residues
  • Role of statistical tools in method validation
  • Overview of  the roadmap from development to formal validation of analytical procedures
Specificity of measurement method
  • Interference with excipient residues, degradation product, and cleaning residue
  • Interference with swab extractables
  • Interferences in analytical samples
  • Quantitative aspect of specificity
Accuracy (incl. practising with Excel)
  • Swab Recovery Studies on coupons
  • Rinse Recovery Studies on coupons
  • Solvent Sampling from hoses
  • Accuracy of the Measurement Method
Precision of measurement method (incl. practising with Excel)
  • Method Repeatability
  • Intermediate Precision
  • Combined analysis of Repeatability/Intermediate Precision with One-way ANOVA
Detection and Quantitation Limits of measurement methods (incl. practising with Excel)
  • By ICH, EP and USP methods
  • of TOC method
  • of HPLC method
  • Visual detection Limit (VDL)
Linearity of measurement method (incl. practising with Excel)
  • ICH requirements (Correlation coefficient, residual SS, residuals plot)
  • Considerations (number of data points, of repeats, quality of fit to linearity, etc.)
  • Analysis of plot of measured vs. actual concentrations
  • Correlation between Cleaning Validation and Monitoring: Relative TOC response factor of Target Residue/Reference Standard in TOC method
Range
  • Range on swab and rinse samples
  • Range of analytical samples
Robustness
  • Robustness factors for sampling recovery
  • Robustness factors for measurement method
  • by DOE matrix Solvent Sampling from hoses
Validation of sampling recovery (incl. practising with Excel)
  • Validation of swab and rinse sampling recovery
  • What Spiking levels?
  • How many replicates?
  • Acceptance criteria
  • Should you correct for recovery?
  • Validation of Visible Residue Level (VRL)
  • Examples of statistical recovery data analysis
Documentation of method Validation
  • Writing a protocol
  • Writing a report

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