LABORATORY AND ANALYTICAL CONTROLS

Inhaltsverzeichnis

1.) SAMPLING
1.1 Requirements; 1.1.1 Personnel; 1.1.2 Equipment; 1.1.3 Containers; 1.1.4 Premises
1.2 Sampling plan (instructions)
1.3 Notes for the identifivation labeling; 1.3.1 Containers and identification labeling; 1.3.2 Sampling report; 1.3.3 Reference samples
2.) REAGENTS
2.1 Labeling
2.2 Usage and stability
2.3 Documentation
3.) STANDARDS AND REFERENCE SUBSTANCES
3.1 Definition of different standards and their areas of use
3.2 Handling, storage and stability
4.) QUALIFYING LABORATORY INSTRUMENTS
4.1 Qualification protocols and reports; 4.1.1 Design qualification (DQ), 4.1.2 Installation qualification (IQ); 4.1.3 Operational qualification (OQ); 4.1.4 Performance qualification (PQ)
4.2 System suitability test (SST)
5.) CALIBRATION IN THE LAB
5.1 Definitions; 5.1.1 Persons; 5.1.2 Instruments; 5.1.3 Working; 5.1.4 Laboratory Equipment Inventory List
5.2 Calibration instructions and record; 5.2.1 Test intervals, test points, test instructions
5.3 Examples; 5.3.1 Balance; 5.3.2 Volume measuring instruments; 5.3.3 Photometer; 5.3.4 HPLC system
5.4 Decision 5.4.1 Requirements, tolerances, specifications; 5.4.2 Equipment release; 5.4.3 Out of calibration
6.) VALIDATION OF ANALYTICAL METHODS
6.1 Principles
6.2 Definitions of the parameters; 6.2.1 Precision; 6.2.2 Accuracy; 6.2.3 LOD = Limit of Detection; 6.2.4 LOQ = Limit of Quantitation; 6.2.5 Selectivity; 6.2.6 Linearity, Range; 6.2.7 Robustness
6.3 Documentation
6.4 Revalidation
7.) STABILIY TESTING
7.1 ICH guidelines for stability tests
7.2 Storage and storage conditions; 7.2.1 Standard storage conditions; 7.2.2 Packaging; 7.2.3 Sample quantities; 7.2.4 Stress test; 7.2.5 Freeze test; 7.2.6 Temperature cycling test; 7.2.7 Special storage conditions for drug products; 7.2.8 Labeling
7.3 Analyses; 7.3.1 Test parameters; 7.3.2 Reference samples; 7.3.3 Consumption test; 7.3.4 Compatibility test for injection solutions for infusions; 7.3.5 Analysis of compatibility of rubber stoppers and plastic components; 7.3.6 Photostability (ICH Q1B); 7.3.7 Microbiological analyses; 7.3.8 Analysis of standing times; 7.3.9 Analysis of transport conditions
7.4 Reduction of the study design; 7.4.1 Bracketing; 7.4.2 Matrixing
7.5 Stability testing in the marketing phase; 7.5.1 Follow-up stability testing (FuST); 7.5.2 Stability commitment (SC)
7.6 Defining the retest period for an active pharmaceutical ingredient and the self lift for a druf product through evaluation of stability data (ICH Q1E): 7.6.1 Data evaluation for the retest period for APOs and shelf life for drug products that are intended for storage at rom temperature; 7.6.2 Data evaluation for retest period for APIs and shelf life for drug products intended for storage in refrigerator (2-8C); 7.6.3 Data evaluation for retest period for APIs and shelf life for drug products for intended storage in a freezer (-20C)
7.7 Decision tree for data evaluation for retest period or for APIs or drug products (excluding frozen products)
7.8 Procedure for statistical analysis
7.9 Examples of the statistical evaluation of stability data; 7.9.1 Data analysis for a single batch; 7.9.2 Data analysis of one attribute in each batch for several batches of the same product (known as One-
Factor, Full-Design Studies); 7.9.3 Data analysis of all attributes for several batches (Multi-Factor, Full-Design Studies)
8. OUT-OF-SPECIFIVATION RESULTS
8.1 Signigicance; 8.1.1 The BARR Laboratories case; 8.1.2 The consequences
8.2 Definitions
8.3 FDA OOS Guidance
8.4 Example for handling of an OOS result
8.5 Trend tracking
9. RAW DATA DOCUMENTATION
9.1 Principles
9.2 Single sheet documentation system; 9.2.1 Cover sheet; 9.2.2 Data sheet; 9.2.3 Index sheet
10. BATCH RELEASE
10.1 Certification by a Qualified Person and release in accordance with EC GMO Guidelines; 10.1.1 Regulations contained in Directive 2001/83/EC; 10.1.2 Objectives of appendix 16; 10.1.3 Cases of application
10.2 Responsibility for issuning the release
10.3 Publication of release
10.4 Release procedures in practice
11. MICROBIOLOGICAL TESTING
11.1 Total microbial count; 11.1.1 Determination of the total microbial count; 11.1.2 Product testing; 11.1.3 Culture merdia and culture media checks; 11.1.4 Incubation; 11.1.5 Evaluation; 11.1.6 Validation of the method
11.2 Specified microorganims; 11.2.1 Detection of specified microorganims; 11.2.2 Detection method for the specified microorganisms; 11.2.3 Evaluation; 11.2.4 Culture media and culture media tests; 11.2.5 Suitablility test of the method (validation of the methods)
11.3 Testing frequencies; 11.3.1 Preparations; 11.3.2 Raw materials
11.4 Miscellaneous test; 11.4.1 Monitoring of the hygiene status; 11.4.2 Aseptic working conditions