3-ICH-guidelines-6th-Sem.pdf

Quality assurance first unit Ich guidelines

1. ICH
Purpose, participants, process of
harmonization, Brief overview of QSEM,
with special emphasis on Q-series
guidelines, ICH stability testing guidelines
INTERNATIONAL COUNCIL FOR
HARMONIZATION

2. ICH Guidelines : Inception 1990
International council for harmonization, earlier Conference
Technical requirement for pharmaceuticals for human use
Step to bring regulatory authorities & Pharmaceutical
Industry to discuss scientific & technical aspects of drug
registration
Mission of ICH: To achieve greater harmonization worldwide
to ensure safe, effective, high quality medicines are
developed/registered in most resource & effective manner

3. PURPOSE OF ICH GUIDELINES
Registration & maintenance of Pharmaceutical product
registration
To have dialogues on scientific issues b/w regulatory
authorities & Pharmaceutical Industry for harmonization of
technical requirements of Pharm. product
Contribute to public health
Monitor & update harmonized technical requirements, leads
to mutual acceptance of R& D data
To avoid various future requirements through harmonization
of selected topics
Facilitate adoption of new or improved technical R&D
approaches, replacing or updating current practices

4. Implementation & integration of common standards by
dissemination of the communication of information about
and coordination of training on harmonized guidelines &
their use
To develop policy for ICH medical dictionary for
regulatory activities terminology (MedDRA)-share
regulatory information internationally for medicinal
products
Process of harmonization: 4 categories
Formal ICH procedure
Q & A procedure
Revision procedure
Maintenance procedure

5. New Topic for
harmonization of ICH
Formal ICH
Procedure
Concept paper
& business plan
required
Clarification
needed for existing
ICH
Q & A
procedure
Concept paper
required Business
plan required
Content of an
existing ICH out of
date or no longer
valid Revision
Procedure
Concept
paper
required
New information to
be added to an
existing ICH G
Change to be made
either toQ3C
guidelines or M2
recommendations
Maintenance
Procedure
Proposal/concept paper required
for Q3C maintenance. No concept
paper required for M2
recommendations maintenance
Business plan outlines includes costs & benefits of harmonizing topic proposed by
concept paper

6. 4 Categories of ICH topics
Quality Guidelines
Includes Stability studies, thresholds for
impurities testing, flexible approach for
pharm. quality based GMP risk
management
Safety Guidelines
To uncover potential risk like
carcinogenicity, genotoxicity,
reprotoxicity
Efficacy Guidelines
Concerned with design, conduct, safety
& reporting of clinical trials
Novel medicines derived from biotech
processes, use of pharmacogenetics
genomic tech. to produce targeted
medicines
Multidisciplinary Guidelines
Includes ICH medical terminology
MedDRA, common tech. document
CTD, development of electronic
standards for transfer of regulatory
information ESTRI

7. BRIEF OVERVIEW OF QSEM
Q series: Quality Guidelines are
Q1A-Q1F: Stability
Q2-Analytical validation
Q3A-Q3D –Impurities
Q4A-Q4B-Pharmacopoeias
Q5A-Q5E-Quality of Biotechnological products
Q-6A-Q6B-Specifications
Q7 –GMP
Q8 Pharmaceutical Development
Q9 Quality risk management
Q10-Pharmaceutical Quality System
Q11 Development & Manufacture of Drug substances
Q12 Life cycle Management
Q13 Continuous Manufacturing of Drug substances & drug products
Q14 Analytical Procedure Development

8. S1A-S1C-Carcinogenicity studies
S3A-S3B-Toxicokinetics& Pharmacokinetics
S4-Toxicity testing
S5 Reproductive testing
S6 Biotechnological Product
S7A-S7B-Pharmacology studies
S8-Immunotoxicologystudies
S9 Non clinical evaluation of anticancer pharmaceuticals
S10 Photosafety
S11 Non clinical pediatric safety
Safety Guidelines S Series

9. Efficacy Guidelines E SERIES
E1-Clinical safety for drugs used in long term treatment
E2A-E2F-Pharmacovigilance
E3 Clinical study reports
E4-Dose response studies
E5 Ethnic factors
E6 Good clinical practice
E7 Clinical Trials in Geriatric population
E8 General considerations for clinical trials
E9 Statistical Principles for clinical Trials
E10 Choice of control group in clinical trials

10. Efficacy Guidelines E SERIES
E11 –E11A Clinical Trials in pediatric population
E12 Clinical Evaluation by Therapeutic category
E14 Clinical Evaluation of QT (Wave, effect on Heart)
E15 Definitions in Pharmacogenetics/ Pharmacogenomics
E16 Qualification of Genomic Biomarkers
E17 Multi Regional Clinical Trials
E18 Genomic Sampling
E19 Safety DATA Collection

11. Multidisciplinary guidelines M series
M1 MedDRATerminology
M2 Electronic standards
M3 Non clinical safety studies
M4 Common Technical Document
M5 Data Elements and standards for drug dictionaries
M6 Gene Therapy
M7 Mutagenic impurities
M8 Electronic common Technical document (eCTD)
M9 Biopharmaceuticsclassification based biowaivers
M10 BioanalyticalMethod development
M11 Clinical electronic structured harmonized protocol
(CeSHarP)

15. Special emphasis on Q series
Q1A R2Stability testing of new drug
substances & products (NDSP)
SEP. 1994
Rev.2001
Feb 2003
Harmonize Intermediate storage
condition for Zone 1 & II with
long termcondition for Zone III
& IV recommended in Q1F
(Stability data package for reg.
applications in climatic zones III
& IV)
Climate
zones
Countries Def Storage conditions
Temp. Humidity
I
II
III
IV
Japan, UK, North Eur. Canada,
Russia, USA etc
Japan South EurUSA etc
Iran Iraq Sudan etc
Brazil Ghana Indonesia
Nicaragua Philippines India Pak
Bangladesh
Temperate
Sub Trop
Mediter.
Hot dry
Tropical
21 °C
25°C
30°C
30°C
45%
60%
35%
70%

16. Variety of Env. factors-affecting quality of drug
Stress testing: degradation products, intrinsic stability of molecule
Includes effect of temp in 10°C increment 50, 60 etc, humidity 75%
RH or greater, oxidation, photolysis
Susceptibility to hydrolysis over wide pH range in solution/ suspension
Photostabilitytesting described in Q1B
Frequency of testing: For long term studies: at least 12 months-
every 3 month over first yr and every 6 months over second yr &
annually thereafter
At accelerated storage condition minimum three time points including
initial and final time points (0,6,9,12 months) from a 12 month study

17. Storage conditions
Test the thermal stability, sensitivity to moisture
During storage, shipment, subsequent use
General case:
3 primary batches-12 month duration
Long term: 12 M-25°C±2°C/60%RH ±5% RH or
30°C±2°C/65%RH ±5% RH
Intermediate:6 months 30°C±2°C/65%RH ±5% RH
Accelerated: 40°C±2°C/75%RH ±5% RH
If long term studies show significant changes during 6 months-
accelerated & intermediate studies to be done

18. Storage in refrigerator
Long term: 5°C±3°C 12 months
Accelerated: 5°C±2°C/60% ±5 RH 6 months
If significant change: b/w 3-6 months-accelerated storage
testing to be done
In a freezer:
Long term -20°C±5°C 12 months
For below -20°C treat on case by case basis
Evaluation: if batch to batch variation is small, combine data in
one overall estimate
Statement/ Labeling
Storage statement on label-based on stability evaluation
Storage conditions