Good Laboratory Practice (GLP) Lecture 12 PDF

Good Laboratory Practice BIOT6002: Lecture 12 Lecturer: Caroline A Browne, Ph.D. Learning Objectives Define GLP GMP Describe sources of error in GLP Good Laboratory Practice (GLP) & Good Manufacturing Practice (GMP) Internal quality control (IQC) procedures are designed to detect &...

Good Laboratory Practice BIOT6002: Lecture 12 Lecturer: Caroline A Browne, Ph.D. Learning Objectives Define GLP GMP Describe sources of error in GLP Good Laboratory Practice (GLP) & Good Manufacturing Practice (GMP) Internal quality control (IQC) procedures are designed to detect & 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 which is involved in generating as analytical result. Good Manufacturing Practice (GMP) ensure that manufactured products meet quality standards by setting specifications and requirements for the process by which they are produced and tested. Gool Laboratory Practice (GLP) Quality management programs First adopted in 1972 in Denmark and New Zealand. US Food and Drug Authority (FDA) released GLP regulations in 1978-79. EMA regulates GLP for the EEC. Directive 2004/9/EC and Directive 2004/10/EC. To ensure testing in a preclinical or product development context is done using reliable methods and excellent recordkeeping so that companies can provide regulatory bodies with accurate and auditable data. Applied to premarket or preclinical research and testing in regulated industries including pharmaceuticals, animal health products and medicated feed, food additives, medical devices, and food packaging. Good Manufacturing Practice (GMP) In the US, GMPs are Food and Drug Administration (FDA) regulations that apply to the manufacture of pharmaceuticals, medical devices, some foods, dietary supplements, and a few other products. GMP regulations are far-ranging and apply to not only testing but every step of the manufacturing process. The focus is on promoting consumer safety by preventing things like cross-contamination, microbial contamination, or lack of drug efficacy due to problems in the manufacturing process. In the US, “current GMP” (cGMP) is a synonym for GMP, as cGMPs specify the FDA’s minimum requirements for manufacturers. The FDA adopted the term “current GMP” to emphasize that manufacturers need to continually re- evaluate their manufacturing practices to stay up-to-date as technology changes in their industry. EMA regulations for GMP Regulation No. 1252/2014 applying to active substances for human use; Directive 2001/83/EC and Directive (EU) 2017/1572, applying to medicines for human use; Directive 91/412/EEC and Regulation (EU) 2019/6 applying to medicines for veterinary use. Directive 2001/20/EC and Regulation (EU) 536/2014 applying to Investigational medicinal products. Five Ps of GMP (US) People involved in manufacturing must be trained in cGMPs and in their roles and responsibilities in maintaining quality. Products must be produced according to the standard operating procedures (SOPs) and must be appropriately tested before release to consumers. Processes should be well-designed, well-documented, and understood by all employees Procedures must be standardized and maintained throughout the manufacturing process. Premises should be designed to reduce the risks of contamination and accidental mislabelling. There are requirements for washing facilities, sewage, lighting, and plumbing. Testing equipment accuracy, sensitivity, specificity, and reproducibility must be documented and must meet specifications. 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 GLPs focus on product development, and GMPs focus on production. GLPs ensure pre-market data integrity - testing that occurs during product development. Roots in pharmaceutical industry, during preclinical drug development and the generation of data for submission to obtain drug approval. GLPs also apply to food and colour additives, food packaging, food contamination limits, and medical devices, since developers of these products need to submit data to gain regulatory approval as well. GMP regulations apply when products are being manufactured to be sold to consumers Used for lot or batch testing, testing of ingredients from suppliers, and any other testing that occurs during manufacturing. GLP – Sources of Error 1. Equipment: Written instructions should be located with equipment (SOPs) Laboratory should have program of regular inspections, calibration, preventative maintenance Good records help locate sources of error GLP – Sources of Error Common laboratory equipment faults: Pipettes, dispensers – contaminated, dirty or incorrectly calibrated Centrifuges – dirty, imbalanced Spectrophotometers – shift in l accuracy, stray light, changes in temperature Cuvettes – dirty, scratched, mismatched pH meters – improper calibration, temperature effects GLP – Sources of Error 2. Procedures All methods must be standardised, fully documented & appropriate for analysis Standard Operating Procedures (SOPs) should be available & contain details of sample handling, analytical procedures & QC measures & equipment to use. Reagents & standards: impurity, instability, improperly prepared, inadequately labelled, incorrectly stored, contamination GLP – Sources of Error 3. Staff Must be trained with correct responsibilities, techniques, SOPs, use of equipment, record keeping. 4. Data: Calculations: correct dilution factors, calculation errors, correct units Reports: transcribing errors of data, misunderstanding of units, report legible and correct, easy to interpret. FDA guidelines on Analytical Method Validation & Control Validating the analytical method ensures that the data are reliable by addressing certain key questions, including: Does the method measure the intended analyte? For example, does anything interfere with the measurement, and is the method specific or selective for the analyte? What is the variability associated with these measurements? For example, what are the accuracy and precision of the method? What is the range in measurements that provide reliable data? For example, what is the sensitivity of the method (e.g., what is the lower limit of quantitation (LLOQ) of the method, and what is the upper limit of quantitation the method (ULOQ)?) FDA guidelines on Analytical Method Validation & Control How do sample collection, handling, and storage affect the reliability of the data from the bioanalytical method? For example, what steps need to be followed while collecting samples? Do the samples need to be frozen during shipping? What temperatures are required to store the samples, and how long can the samples be stored? Method development includes the optimization, validation & control of the following bioanalytical parameters: Reference standards Critical reagents Calibration curve Quality control samples (QCs) Selectivity and specificity Sensitivity Accuracy Precision Recovery Stability of the analyte in the matrix U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) May 2018 Biopharmaceutics Learning Objectives Define GLP GMP Describe sources of error in GLP