DETERMINATION OF RELATED SUBSTANCES & IMPURITIES IN DRUGS BY ICH GUIDE LINES

BY M.PAUL RICHARDS

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.

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)

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.

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.

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.

For Isolating and Identifying process related Impurities using

MS NMR HPLC FTICR-MS LC-MS.

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.

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.

CO SPONSORS OF ICH.

EC-EU. EFPIA. MHW JPMA FDA PRMA

FUNCTIONS.

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

WHO GOVERN ICH

1.Six founder members of ICH. 2.OBSERVERS:

A.WHO B.EFTA

C.HPB

3.SECRETERIATES (PROVIDED BY JFPMA)

AREAS OF ICH GIDELINES

STABILITY. ANALYTICAL VALIDATION. IMPURITIES. PHARMACOPOEIAS. BIOTECHNOLOGICAL QUALITY. GMP. TOXICITY. KINETICS. REPRODUCTIVE KINETICS. CARCINOGENCITY.

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”

Individual Harmonisation topics

Safety. Quality Efficacy Multidisciplinary

Status of ICH GUIDE LINES:

EFFICIENCY TOPICS

GENERAL CLASS

ICH CODE GUIDE LINE TITLE

ICH STAGE

EXPOSURE E1 The extent of population exposure to assess clinical safety

5

Clinical safety E2E2A

E2B

Def & sds for expedited reporting.Data elements for transmission of adv.drug reactions.

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5

Study reports

E 3 Clinical study reports str &format

5

Dose response

E4 Dose response & information

5

Clinical trial Designs.

E8E9E10E11

Gen consideratiStatisticalChoice of controlGroups.Clinical trials in children

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1

SAFETY TOPICS

Carcinogenicity

S1S1AS1BS1C

Need for CarcinogenicityTesting for c.gencity.Dose selection.

55

5

Genotoxicity S2S2AS2B

Specific aspect fRegulatory test.std tests.

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Kinetics S3S3 AS3 B

ToxicokineticsPhar.kinetics.

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Reproductive toxicity

S5S5 AS5 B

Toxicity to reproductionMale fertility.

5

QUALITY TOPICS

Quality topics

Q1Q1AQ1BQ1C

Sta tes’g f new dr’s& prod’s.Photo stability testing.Stability testing of new formulation.

15

5

Analytical Validation.

Q2Q2 A

Def ,technology& methodology

5

Pharmacia's Q4 Pharmacopoeilharmonisation

5

GMP Q7Q7A

GMP for APIS

1

Impurity Q3Q3A

Impurity on new drug sub’ces &dosage for’s

55

Selection of Topics

Step 1Step 2Step 3Step 4Step 5

BY