1. DETERMINATION OF RELATED SUBSTANCES & IMPURITIES IN DRUGS BY ICH GUIDE LINES BY M.PAUL RICHARDS

2. INTRODUCTION ANALYTICAL PROCEDURES. RESIDUAL SOLVENTS ICH GUIDELINES CO - SPONSORS OF ICH. WHO GOVERN ICH AREAS OF ICH GUIDE LINES. THE STATUS OF ICH GUIDE LINES.

3. ANALYTICAL PROCEDURES Suitable for detection & quantification of degradation products. (HPLC & TLC). For determination of related substances & degradation products. Sample stored under stress conditions (light, heat, humidity, acid/base hydrolysis & oxidation)

4. Other peaks should be labelled in the chromatogram & discussed in documentation. Quantification limit is >/ the reporting threshold. Deg.product should be compared with analytical response of Deg.product to that of appropriate REFERENCE STD. REFERENCE STD : Control of deg.products should be evaluated & to their Intended use.

5. Should be validated for specified & unspecified conditions & used to estimate,identify & unidentify deg.products. Diff.used during development proposed to commercial product should be discussed.

6. RESIDUAL SOLVENTS Determine by using C.Technique such as GC. Those describe in pharmacopoeias can be used for determination. If only class 3 solvents are present,non specific method used on loss on drying.

7. For Isolating and Identifying process related Impurities using MS NMR HPLC FTICR-MS LC-MS.

8. ICH GUIDELINES (INTERNATIONAL CONFERENCE ON HARMONIZATION) DEF: This is a process by which the organising authorities of the US, European commission Japan & experts from pharmaceutical industries & the trade association in the three region are brought together to discuss about the scientific and technical aspects of PRODUCT REGISTRATION.

9. OBJECTIVE To discuss scientific & technical aspects of medicinal product registration. Discuss b/w regulatory authorities and the pharmaceutical industry on the real and perceived differences. To identify an area where modification in technical requirements could lead to a more economical use. To make recommendations on practical ways. To achieve greater harmonisation in interpretation & application of technical guidelines & requirements for registration.

10. CO SPONSORS OF ICH. EC-EU. EFPIA. MHW JPMA FDA PRMA

11. FUNCTIONS. HAS EQUAL PARTICIPATION IN THE PROCESS & EACH HAS TO SEAT ON THE STEARING COMMITTEE, WHICH OVERSEAS HARMONISATION ACTIVITIES.

12. WHO GOVERN ICH 1.Six founder members of ICH. 2.OBSERVERS: A.WHO B.EFTA C.HPB 3.SECRETERIATES (PROVIDED BY JFPMA)

13. AREAS OF ICH GIDELINES STABILITY. ANALYTICAL VALIDATION. IMPURITIES. PHARMACOPOEIAS. BIOTECHNOLOGICAL QUALITY. GMP. TOXICITY. KINETICS. REPRODUCTIVE KINETICS. CARCINOGENCITY.

14. 4 EWG is further divided into a member of working topic groups for which a RAPPORTEUR. STEERING COMMITTEE IS ADVISED BY EXPERT WORKING GROUP ON TECHNICAL ISSUES. On the basis of “CONCEPT PAPER”

15. Individual Harmonisation topics Safety. Quality Efficacy Multidisciplinary

16. Status of ICH GUIDE LINES: EFFICIENCY TOPICS

17. GENERAL CLASS ICH CODEGUIDE LINE TITLE ICH STAGE EXPOSURE E1The extent of population exposure to assess clinical safety 5 Clinical safety E2 E2A E2B Def & sds for expedited reporting. Data elements for transmission of adv.drug reactions. 555555

18. Study reports E 3 Clinical study reports str &format 5 Dose response E4 Dose response & information 5 Clinical trial Designs. E8 E9 E10 E11 Gen considerati Statistical Choice of control Groups. Clinical trials in children 55115511

19. SAFETY TOPICS

20. Carcinogenicity S1 S1A S1B S1C Need for Carcinogenicity Testing for c.gencity. Dose selection. 555555 Genotoxicity S2 S2A S2B Specific aspect f Regulatory test. std tests. 5555 Kinetics S3 S3 A S3 B Toxicokinetics Phar.kinetics. 5555 Reproductive toxicity S5 S5 A S5 B Toxicity to reproduction Male fertility. 5

21. QUALITY TOPICS

22. Quality topicsQ1 Q1A Q1B Q1C Sta tes’g f new dr’s& prod’s. Photo stability testing. Stability testing of new formulation. 155155 Analytical Validation. Q2 Q2 A Def,technology& methodology 5 Pharmacia'sQ4Pharmacopoeil harmonisation 5 GMPQ7 Q7A GMP for APIS1 ImpurityQ3 Q3A Impurity on new drug sub’ces &dosage for’s 5555

23. Selection of Topics Step 1 Step 2 Step 3 Step 4 Step 5

24. BY