Central Research Institute (CRI), Kasauli Summer Training

1 month industrial training at CRI, Kasauli, Himachal Pradesh which includes production, QC and QA testing of immunobiologicals (vaccines). Different tests carried out in brief, and introduction about their manufacture.

1. Central Research Institute, Kasauli Qa & QC of immunobiologicals Under supervision of :- Dr. Santosh Kutty (CMO/SAG) Ph No.- 01792-273141 Email :- [email protected] Central Research Institute, Kasauli 1

2. Contents About CRI Major products manufactured at CRI How to produce a vaccine Role of QC department Utility montoring at QC lab Role of QA deparment Activities at QA Central Research Institute, Kasauli 2

3. About CRI Founded on 3rd of May 1905 , originally established for manufacture of vaccines and antisera , human resource development . This institute contribut ed towards vaccine production during the period of the Second World War . Presently , it is continuously contributing to the National Health Programme . F irst Central Government Institute to have cGMP compliant infrastructure for vaccine production. Central Research Institute, Kasauli 3

4. Central Research Institute, Kasauli 4 Major products manufactured at CRI DPT Vaccine Tt (Tetanus Toxoid) ARS (Anti-Rabies Serum) ASVS (Anti-Snake Venom Serum) ADS (Anti-Diphtheria Serum)

5. How to produce a vaccine Central Research Institute, Kasauli 5 QC & QA

6. Role of QC Department Release of vaccines/sera Assigning expiry dates to media Preparation and distribution of reference standards Qualification and Validation of equipments at new DPT facility Teaching and training of M.Sc Microbiology students Training of staff and summer training Central Research Institute, Kasauli 6

7. Some important tests Limes Flocculation (Lf) Principle :- Antigen + Antibody = Floccules Irreversibility Test (on Guinea Pigs) Principle :- B ased on toxoids resulting from a formaldehyde-mediated inactivation of tetanus Tetanus test :- Subcutaneous inoculation of toxoid sample and observed for 28 days Diphtheria test :- Transdermal inoculation in shaved Guinea pigs to observe skin reactions for 48 hours Central Research Institute, Kasauli 7 ( Diphtheria toxoid) ( Dph Anti-toxin)

8. MWGT (Mice Weight Gain Test) Principle Comparison between results of tests in mice some of which were treated with vaccine and others with saline 0.5 ml intra-peritoneal inoculum on Swiss albino mice observed for 14 days Abnormal Toxicity test Principle Testing toxicity of any abnormal substance in vaccine Direct 2.5 ml vaccine inoculum without dilution inoculated in Guinea pigs Observation period 7 days Central Research Institute, Kasauli 8

9. Utility monitoring at QC Lab Water Monitoring MPN CFU Endotoxin Test (LAL Test) Biochemical Analysis (pH, conductivity, hardness, Cl, Mg, Ca, etc.) Environment Monitoring Viable air sampling Non-viable particle counting Personnel & Surface Monitoring Finger dab plating Contact plate method Central Research Institute, Kasauli 9

10. Water Monitoring MPN (Most probable no.) Principle Random dispersion of m/o. per volume of a given sample in liquid media Different volumes of water is added to tubes containing MacConkey broth growth media Colour change indicates presence of micro-organisms CFU (Colony forming units) Principle Measure the viable bacterial/fungal cells in given sample in solid media Central Research Institute, Kasauli 10

11. Endotoxin test/LAL test Principle Addition of a solution containing endotoxin to a solution of lysate produce turbidity after incubation at 37°C for 1hr Negative control LAL Reagent water (100 µL ) No gel formation Test sample 100 µL water sample + LAL reagent (100 µL ) Gel formation observed by tilting tube at 120° Positive control Pure E.Coli inoculum + LAL reagent (100 µL ) Gel formation Central Research Institute, Kasauli 11

12. Environment monitoring Viable air sampling Testing for detection of bacteria, yeast and mould Non-viable particle counting Central Research Institute, Kasauli 12 Check the no. of particles of 0.5-5 μ m size Volumetric air sampler

13. Personnel & Surface Monitoring Surface monitoring Contact plate method Swab sampling Personnel Monitoring Central Research Institute, Kasauli 13

14. Role of QA Department Q ualification of raw material, vendors, testing methods Ensuring tha t deviations are documented, reviewed and analyzed P ersonnel recruitment and training, data recording , m anage Inputs Training and leading the internal audit team for each department Reviewing and approving manufacturing records and QC testing data Central Research Institute, Kasauli 14

15. Components of QA Strategic level :- Long term decision of quality/policies Tactical level :- Medium term trainings, facilities and operation of QA Operational level :- Day to day operations (SOPs, working) Objectives Mananging cGMP Managing GLP Managing safety programme Assuring the quality of raw materials Central Research Institute, Kasauli 15

16. Activities in QA Central Research Institute, Kasauli 16 Planning Data collection (scope, time, Cost) Documentation Quality control (SOPs, Protocols (Inspection, Of test, Results, ensure quality Report) of product) Evaluation Reporting activities

17. References https://crikasauli.nic.in/ https://www.ncbi.nlm.nih.gov/pubmed/3918350 https://www.vaccineseurope.eu/about-vaccines/key-facts-on-vaccines/how-are-vaccines-produced/ http://www.pharmamicroresources.com/2018/11/avoiding-environmental-monitoring-false.html Central Research Institute, Kasauli 17

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