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Good Laboratory Practice (GLP) & Good Manufacturing Practice (GMP)

• Internal quality control (IQC) procedures are designed to detect and distinguish between systematic and random error.
• The source of error must be identified to eliminate it.
• Good Laboratory Practice (GLP) involves all aspects of the laboratory involved in generating an analytical result.
• Good Manufacturing Practice (GMP) ensures manufactured products meet quality standards by setting specifications and requirements for the production and testing process.

Learning Objectives

• Define GLP
• Define GMP
• Describe sources of error in GLP

GLP - Sources of Error: Equipment

• Written instructions (SOPs) should be located with the equipment.
• Laboratories should have a program of regular inspections, calibration, and preventative maintenance.
• Good records help locate sources of error.
• Common equipment faults include contaminated or incorrectly calibrated pipettes and dispensers, dirty or imbalanced centrifuges, spectrophotometer inaccuracies (stray light, temperature changes), mismatched or dirty cuvettes, and improperly calibrated pH meters with temperature effects.

GLP - Sources of Error: Procedures

• All methods must be standardized, fully documented, and appropriate for analysis.
• Standard Operating Procedures (SOPs) should be available and contain details on sample handling, analytical procedures, and quality control (QC) measures and equipment use.
• Reagents and standards must be carefully checked for impurities, instability, improper preparation, inadequate labeling, incorrect storage, and contamination.

GLP - Sources of Error: Staff

• Staff must be trained with correct responsibilities, techniques, standard operating procedures (SOPs), and equipment use, as well as record-keeping.

GLP - Sources of Error: Data

• Calculations must be accurate, including correct dilution factors, calculation errors, and correct units.
• Reports must be accurate, including transcribing errors of data, and avoiding misunderstandings of units and ensuring reports are legible and easy to interpret.

FDA Guidelines on Analytical Method Validation & Control

• Validating an analytical method ensures data reliability by addressing key questions:
  • Does the method measure the intended analyte? (e.g., interference, specificity)
  • What is the variability associated with measurements? (e.g., accuracy, precision)
  • What is the range in measurements that provide reliable data? (e.g., sensitivity, lower and upper limits of quantitation (LLOQ and ULOQ))
• Sample collection, handling, and storage affect data reliability.
• Method development includes optimization, validation, and control of parameters like:
  • Reference standards
  • Critical reagents
  • Calibration curve
  • Quality control samples (QCs)
  • Selectivity and specificity
  • Sensitivity
  • Accuracy
  • Precision
  • Stability of the analyte, and matrix.

GMP Regulations in the EU & EMA

• Regulation No. 1252/2014 applies to active substances for human use.
• Directive 2001/83/EC and Directive (EU) 2017/1572 apply to medicines for human use.
• Directive 91/412/EEC and Regulation (EU) 2019/6 apply to medicines for veterinary use.
• Directive 2001/20/EC and Regulation (EU) 536/2014 apply to Investigational medicinal products.

Five Ps of GMP (US)

• People: Training in cGMPs and responsibilities for maintaining quality.
• Products: Produced according to standard operating procedures (SOPs) and appropriately tested before release.
• Processes: Standardized and maintained throughout manufacturing.
• Procedures: Well-designed, documented, and understood by all employees.
• Premises: Designed to reduce risks of contamination and accidental mislabeling. Requirements include washing facilities, sewage, lighting, and plumbing, meeting documented specifications for accuracy, sensitivity, specificity, and reproducibility.

GMP Requirements in the EU

• Quality Management
• Personnel
• Premises & equipment
• Documentation
• Production
• Quality control
• Contract manufacturing & analysis
• Complaints & product recall
• Self-inspection

GLP v's GMP

• GLP focuses on pre-market product development and data integrity (testing), while GMP focuses on production.
• GLP roots are in pharmaceutical industry preclinical drug development and data generation related to obtaining drug approval.
• GLPs apply to food and colour additives, food packaging, food contamination limits, and medical devices.
• GMP regulations apply when products are being manufactured for sale.
• GMP involves lot or batch testing, testing of ingredients from suppliers, and any testing during manufacturing.

This quiz covers the essential principles of Good Laboratory Practice (GLP) and Good Manufacturing Practice (GMP). Focus on internal quality control, identifying sources of error, and the importance of maintaining equipment standards. Test your understanding of the definitions, objectives, and critical practices in laboratory settings.