Good Laboratory Practices Pharmaceutical Quality Assurance

Good Laboratory Practices

1. 4.8.7 T QUALITY ASSURANCE TECHNIQUES SAVITRIBAI PHULE PUNE UNIVERSITY Syllabus of Final Year B. Pharmacy (EFFECTIVE FROM ACADEMIC YEAR 2018-19) PATTERN 2015

2. Hello! I am Shrikant Kavitake M Pharm (Pharmaceutics) DATTAKALA COLLEGE OF PHARMACY Swami- Chincholi , Daund, Pune . 2

3. 3. GOOD LABORATORY PRACTICES 3 GLP

4. Good Laboratory Practices (GLP) 4 Medicines and Healthcare products Regulatory Agency- UK which defines GLP as: “Good Laboratory Practice (GLP) consists a set of principles that provides a framework within which laboratory studies are planned, performed, monitored , recorded, reported and archived”. The phrase Good Laboratory Practice or GLP specifically refers to a quality system of management controls for research laboratories and organizations to ensure the uniformity , consistency, reliability, reproducibility, quality , and integrity of chemical ( including pharmaceuticals ) non-clinical safety tests; from physiochemical properties through acute to chronic toxicity tests .

5. Contin… 5 These studies are undertaken to generate data by which the hazards and risks to users, consumers and third parties, including the environment, can be assessed for pharmaceuticals (only preclinical studies), agrochemicals, cosmetics, food additives , feed additives and contaminants, novel foods, biocides , detergents etc. GLP helps assure regulatory authorities that the data submitted are a true reflection of the results obtained during the study and can therefore be relied upon when making risk/safety assessments. GLP is an FDA regulation.

6. HISTORY 6 • The term GLP was first used in New Zealand in 1972. • GLP was first introduced in New Zealand and Denmark in 1972, and later in the US in 1978 in response to the Industrial BioTest Labs scandal. • GLP is a formal regulation that was created by the US FDA (United states food and drug administration) in 1978. • GLP was instituted in US following cases of fraud generated by toxicology labs in data submitted to the FDA by pharmaceutical companies. As a result of these findings, FDA promulgated the Good Laboratory Practice (GLP) Regulations, 21 CFR part 58, on December 22, 1978 (43 FR 59986). The regulations became effective June 1979.

7. Cont… 7 Assure the quality and integrity of safety Nonclinical laboratory studies Although GLP originated in the United States, it had a world wide impact. Non-US companies that wanted to do business with the United states or register their pharmacies in the United States had to comply with the United States GLP regulations. They eventually started making GLP regulations in their home countries. CFR : Code of Federal regulations

8. WHY WAS GLP CREATED? 8 • In the early 70’s FDA became aware of cases of poor laboratory practice all over the United States. • FDA decided to do an in-depth investigation on 40 toxicology labs. • They discovered a lot fraudulent activities and a lot of poor lab practices. • Examples of some of these poor lab practices found were 1. Equipment not been calibrated to standard form, therefore giving wrong measurements. 2. Incorrect/inaccurate accounts of the actual lab study. 3. Inadequate test systems.

9. Example 9 One of the labs that went under such an investigation made headline news. • The name of the Lab was Industrial Bio Test. This was a big lab that ran tests for big companies such as Procter and Gamble . • It was discovered that mice that they had used to test cosmetics such as lotion and deodorants had developed cancer and died. • Industrial Bio Test lab threw the dead mice and covered results deeming the products good for human consumption. • Those involved in production, distribution and sales for the lab eventually served jail time.

10. OBJECTIVES OF GLP 10 GLP makes sure that the data submitted are a true reflection of the results that are obtained during the study. GLP also makes sure that data is traceable. Promotes international acceptance of tests.

11. GLP Principles 11 1 . Organization and Personnel Management-Responsibilities Sponsor-Responsibilities Study Director-Responsibilities Principal Investigator-Responsibilities Study Personnel-Responsibilities 2. Quality assurance program Quality Assurance Personnel 3. Facilities Test System Facilities Facilities for Test and Reference Items 4. Equipment, reagents and Materials

12. Cont… 12 5. Test systems Physical/Chemical Biological 6. Test & Reference items 7. Standard operating procedures 8. Performance of Study Study Plan Conduct of Study 9. Reporting of results 10. Archival - Storage of Records and Reports

13. Basic elements in GLP 13 • Personnel  Sponsor  Management  Study director  Quality Assurance • Facility  Laboratory Operation  Animal care  Equipment  Reagents  Storage • Documents  Standard Operating Protocols  Reports  Archiving • Test and Control Articles  Characterization  Handling  Storage

14. Personnel 14 Qualification of personnel: The assumptions is that in order to conduct GLP studies with right quality a couple of things are important ; 1)There should be sufficient number. 2)The personnel should be qualified . Sponsor : Person who initiates and supports non-clinical laboratory study, a person who submits non-clinical study to FDA or testing facility that initiates and conducts the study . Facility management: Responsibilities of facility management is well defined. They designate a study director, as well as assure quality assurance unit is available, test and control articles are characterized.

15. Cont… 15 Study director: He has overall responsibilities for technical conduct safety studies, as well as interpretation, analysis, documentation and reporting of results. Quality Assurance unit: The quality assurance unit (QAU) serves an internal control function. It is responsible for monitoring each study to assure management that facilities, equipment, personnel , methods, practices, records, controls, SOPs, final reports (for data integrity), and archives are in conformance with the GLP/GALP

16. Facilities 16 • Suitable size, construction and location. • Adequate degree of separation of the different activities. • Isolation of test systems and individual projects to protect from biological hazards . • Suitable rooms for the diagnosis, treatment and control of diseases. • Storage rooms. Apparatus of appropriate design and adequate capacity. • Documented Inspection, cleaning, maintenance and calibration of apparatus. • Apparatus and materials not to interfere with the test systems. • Chemicals, reagent and solutions should be labelled to indicate identity, expiry and specific storage instructions.

17. Cont… 17 Test Systems • Physical and chemical test systems. • Biological test systems. • Records of source, date of arrival, and arrival conditions of test systems. • Proper identification of test systems in their container or when removed. • Cleaning and sanitization of containers. • Pest control agents to be documented .

18. Cont… 18 Test and Reference Items • Receipt, handling, sampling and storage • Characterization. • Known stability of test and reference items . • Stability of the test item in its vehicle (container ). • Experiments to determine stability in tank mixers used in the field studies. • Samples for analytical purposes for each batch.

19. Standard Operating Procedures (SOP) 19 Written procedures for a laboratories program. They define how to carry out protocol specified activities. Most often written in a chronological listing of action steps. They are written to explain how the procedures are suppose to work. Routine inspection, cleaning, maintenance , testing and calibration. Actions to be taken in response to equipment failure. Keeping records, reporting, storage, mixing , and retrieval of data. Definition of raw data. Analytical methods.

20. Performance of the Study 20 • Prepare the Study plan. • Content of the study plan. › Identification of the study. › Records. › Dates. › Reference to test methods. › Information concerning the sponsor and facility. • Conduct of the study.

21. Reporting of Study Results 21 • Information on sponsor and test facility. • Experimental starting and completion dates . • A Quality Assurance Program Statement. • Description of materials and test methods. • Results. • Storage (samples, reference items, raw data , final reports) etc .

22. Storage and Retention of Records and Materials 22 – The study plan, raw data, samples. – Inspection data and master schedules . – SOPs. – Maintenance and calibration data. – If any study material is disposed of before expiry the reason to be justified and documented. – Index of materials retained.

23. Do this for GLP 23 • Keep the things at its location after use. • Store heavy things at bottom & if possible on Trollies . • Give name of location to everything. • Follow “Everything has the place & Everything at its place” principle. • Prepare location list & display it. • Put ladders for things stored on top. • Identify everything with its name/ purpose. • Follow “FIFO” to prevent old accumulation for laboratory chemicals.

24. Benefits of GLP 24 • It will give better image of company as a Quality producer in Global market. • Provide hot tips on analysis of data as well as measure uncertainty and perfect record keeping. • Provide guideline for doing testing and measurement in detail. • Provide guidelines and better control for maintenance of instruments, environment control, preservation of test records etc .

25. Thanks! Any questions? You can find me at [email protected] [email protected] 25