Safety Data Generation.pptx Safety data generation

Safety data generation
 Pre clinical phase
 Clinical phase
 Post approval phase (PMS)

1. Communication in Pharmacovigilance

2. Safety Data Generation

3. Safety data generation Drug D isco v ery Pre- Clinical D e v elo p m ent Clinical D e v elopm ent R egulatory approval Drug M arketed IND Application Developed Compound NDA Submission Drug Approved for marketing P re-C l in i ca l Phase Post A ppro v al Phase C l inical Phase 1 2 3

4. Safety data generation In-vitro, In-vivo Safety pharmacology AEs/SAEs Subject Follow-ups PSURs Marketing authorization holders ( M AH) AEs Pre-Clinical Phase Clinical Phase Post Ap p roval Phase

5. Pre-Clinical Phase 4

6. Pre-Clinical Phase Data Generation ◎ Exp l oratory t o x i col o gy: ◎ Regulato ry to x icology

7. Pre-Clinical Phase Data Generation ◎ Explorator y toxicology: Provide a rough quantitative estimate of t o x i city (acute or repeated dose) Pr o vid es main o rgans and sys t ems involved

8. Pre-Clinical Phase Data Generation ◎ Regulator y t o xicology: Per f ormed to GLP s t anda r ds and compri s e regulat o ry requirement by authorities Perfo rmed to suppo r t an appl i cation for marke t i n g appr o val

9. Pre-Clinical Phase Data Generation ◎ Exp l or a to r y to x ico l og y : I n - vi t ro and i n - vi v o stud i es: Mutagenicity Cytotoxicity Immunotoxicity Hepatotoxicity Embryotoxicity

10. Pre-Clinical Phase Data Generation ◎ Regulatory Toxico logy: Safe t y pharmac o logy GLP gui d elines Acute t o x ic i ty Chron i c t o x i ci t y Repro d u c t i ve t o x i city

11. Pre-Clinical Phase Data Generation Safet y p harmacology: Pharmac o log i cal tes t i n g to check that the drug does n o t pro d uce any obvi o usly hazardous acute effects known as safety pharmacology.

12. Pre-Clinical Phase Data Generation Safet y p harmacology: S y s t em w i se tes t s F o ll o w up tes t s Sup p lemen t ary tes t s

13. Pre-Clinical Phase Data Generation Safet y p harmacology: S y s t em w i se tes t s CVS: BP, Heart rate, ECG changes Respi r ato ry: RR, Tid al vo l ume CNS: Behavioural Changes, mo t or act i vi t y, Bo d y tempe r atu r e

14. Pre-Clinical Phase Data Generation Safet y p harmacology: F o ll o w up tes ts CVS: Card i ac out p ut, vent r icular contractility Respira t ory: pulmonary arter i al pres s ure, blo o d gases

15. Pre-Clinical Phase Data Generation Safet y p harmacology: Sup p lemen t ary tes t s: Rena l functio n: Uri n ary vo l ume, pH, pr o te i nuria, blo o d urea GIT: gastr ic secret i on, pH, GI moti li t y, GI tra n sit t i me

16. Pre-Clinical Phase Data Generation Acute t o x i city: 28 days repeat dose to x ic i ty and recovery in 2 species Chro ni c t o x i ci t y: 3 - 12 m on t hs chron i c t o x i city in 2 species

17. Pre-Clinical Phase Data Generation Reproduct i ve t o x i city: Repro d uct i ve t o x i city in 1 species Carcinogenicity: 24 months carcinogenicity in 2 species

18. Clinical Trial Safety Data Generation 17

19. Clinical Trial Safety Data Generation 20–100 People Usually 1-2 Years Phase I (Safety) 100-300 People 1-2 Years Phase II (Efficacy and Safety) 1000-3000 Peoples 2-3 Years Phase III (Efficacy and Safety)

20. Clinical Trial Safety Data Generation Ser i ous adverse e vents repo r ting C o nduc t ing Subjec t s fo llow up Ensuring subject compliance C o n t i n ue communica t i o n

21. Clinical Trial Safety Data Generation Adverse Events U ne x pe ct e d adverse events Any laboratory a b n o r m a l i t i es Serious A d v er s e events Adverse events of special interest Adverse drug reactions

22. Clinical Trial Safety Data Generation Adverse Event: Any untoward medical occurrence observed during treatment while a pharmaceutical product which does not necessarily have a causal re la t ionship wi t h th e trea t m ent. Adv e rse outc o m e s af ter use of the d rug Any new clinical experience may or may not be linked to the use of drug Eg: any laboratory abnormality or new symptoms after the use of the drug

23. Clinical Trial Safety Data Generation Sources: Clinical I nfor m a t ion sourc e s Non Clinical Information Sources

24. Clinical Trial Safety Data Generation Sources: Cl i nica l Informat i o n s o urces: Data from clinical and epidemiological studies Data from pharma c e ut ical c o m pani e s Saf ety p r ofile of th e drug s of similar c l a s s or type Dat a from c l inical st udies

25. Clinical Trial Safety Data Generation Sources: No n Clin i ca l Informat i o n S o urces: Chemical structure, class indication, adverse effects, actions I n - vitro st u di e s r e p ort Data from toxicology studies in animals (Cardiotoxicity, hepatotoxicity, r e nal toxicity, carcinogeni city, mut a genicity)

26. Clinical Trial Safety Data Generation Se r i o us adv e rse event A d ve r se d r ug r e action Unexpected adverse event: Nature and severity of which is not consistent with the risk in form a tion described in general i n ve s ti g at i onal p l an of in v estigator’ s brochure

27. Clinical Trial Safety Data Generation Reporting timeli n es: Any Serious, unexpected or life threatening adverse events must be reported within 7 days Any other unexpected AEs that are neither fatal not life thr e at e ni n g should b e reporte d with i n 15 days

28. Post Marketing Safety Data Generation 27

29. Post Marketing Safety Data Generation Per iod i c safety update rep o rts PSUR Pr o cess Inta ke of ADR in f or ma t ion Data Retri e val Dat a analysis PSURs should be submitted every months for first two yea r s and an n ually f o r su b sequent 2 y ears. ( I nd i a)

30. Post Marketing Safety Data Generation PMS Spontaneous reporting P res c r i pt i on Event Monitoring Electronic health records Obser v at i o n al studies Registries

31. Post Marketing Safety Data Generation Post m a r k e t i n g s a f e t y e v a l uation data so u rce: P r oduct’s pr e appr o val safety p r o f ile Cur r e n t FDA appr o ved lab el FDA adv erse e v e n t rep o rts (FAERS) Repo r ts of vacci ne adve r se ev e nt re p orting system (VAERS) Per iod i c su b mission of safety r ep o rts

32. Post Marketing Safety Data Generation Post m a r k e t i n g r e p or t s timeli n e: Ser i ous and une x pected AEs: FDA re c ommends re p or t to be su b mit t ed with in 15 days Foll o w up - Up to 15 days al e rt r ep o rts should be su b mit t ed with in 15 days