This document discusses ICH guidelines for stability testing and protocols. It provides an overview of the ICH partners that develop guidelines and describes some of the key ICH guidelines related to quality, safety, and efficacy. It then focuses on ICH guideline Q1 which provides recommendations for stability testing of new active pharmaceutical ingredients and finished pharmaceutical products, including stress testing, selection of batches, storage conditions, and photo stability testing. The document also discusses bracketing and matrixing designs for stability testing and outlines what should be included in a stability protocol and report.

1. Presentation of
PHARMACEUTICAL PRODUCT
DEVELOPMENT
 TOPICS:-
 ICH guidelines of
stability testing &
 Protocols
PRESENTED BY
V.GOUTHAMI
Dpt.of Pharmaceutics
MALLA REDDY COLLEGE OF PHARMACY

2. ICH PARTNERS
 EFPIA[European Federation of pharmaceutical
Industries and Associations]
 JPMA[Japan Pharmaceutical Manufactures
Association]
 PhRMA[Pharmaceutical Research and Manufactures
Of America]
 MHLW[Ministry Of Health Labor Welfare]Japan
 USFDA
 EU regulators

3. ICH GUIDELINES
QUALITY :-
 Q1:-Stability testing
 Q2:-Analytical validation
 Q3:-Impurities
 Q4:-Pharmacopoeias
 Q5:-Biotechnological products
 Q6:-Test procedures acceptance criteria
 Q7:-Good manufacturing practices
 Q8:-Pharmaceutical development
 Q9:-Quality risk management
 Q10:-Pharmaceutical quality system

4. SAFETY:-
 S1A:-Guidelines for carcinogenicity studies of
pharmaceuticals
 S1B:-Testing for carcinogenicity of pharmaceuticals
 S1C:-Dose selection
 S2A:-Guidence on genotoxicity tests for
pharmaceuticals
 S3A:-Guidence on toxicokinetic studies

5. •S3B:-Guidance for repeated dose tissue distribution
studies
•S4 :-Chronic toxicity testing in animals(rodents and
non rodent toxicity testing
•S5 :-Detection of toxicity to reproduction for medicinal
products
•S6 :-Preclinical safety evaluation of biotechnology
derived products
•S7A:-Safety pharmacology studies for human
pharmaceuticals
•S7B:-Non clinical evaluation of the potential for dalayed
ventricular repolarisation (QT interval prolongation)by
human pharmaceuticals
•S8 :-Immuno toxicity studies for human
pharmaceuticals
•S9 :-Non clinical evaluation for anti cancer drugs

6. EFFICACY
 E1 :-Clinical safety for drugs intended for long term
treatment
 E2A:-Definitions and standards for expedited
reporting
 E2B:-Data elements for transmission of individual case
safety reports
 E2C:-Periodic safety up date reports for marketed
drugs
 E2D:-Definitions and standards for expedited reports

7. •E2E:-Pharmacovigilance planning
•E3 :-Structure and content of clinical study
reports
•E4 :-Dose-response information to support drug
registration
•E5 :-Ethinic factors in the acceptability of foreign
clinical data
•E6 :-Good clinical practice
•E7 :-Studies in support of special populations
•E8 :-General considerations for clinical trials
•E9 :-Statistically principles for clinical trials
•E10:-Choice of control group and related tissues
in clinical trials
•E11:-Clinical investigations of medicinal products

8. •E12:-Principles for clinical evaluation of new
antihypertensive agent
•E14:-The clinical evaluation of QT interval
prolongation and pro arryhthmic potential for non-anti
arrhythmic drugs
•E15:-Definitions for pharmacogenomics,
pharmacogenetics, genomic data and sample coding
categories
•E16:-Genomic biomarkers related to drug
responds-context structure and format of
qualification submission

9. Q1
 Q1A:-Stability testing of new API $ FPP
 Q1B:-Photo stability testing of new API $ FPP
 Q1C:-Stability testing of new dosage forms
 Q1D:-Bracketing and matrixing designs for stability
testing of API $ FPP
 Q1E:-Evaluation of stability data
 Q1F:-Stability data package for registration in climatic
zones III & IV

10. Q1A:-STABILITY TESTING OF NEW
API$FPP
 Stress testing
 Selection of batches
 Container and closure systems
 Storage conditions

11. Stress testing of API in solution
Storage conditions Testing period*
pH ± 2, room temperature 2 weeks
pH ± 7, room temperature 2 weeks
pH ± 10-12, room temperature 2 weeks
H2O2, 0.1-2% at neutral pH,
room temperature
24 hours

12. Stress testing of FPPs in solid state
Storage conditions Testing period*
40°C, 75 % RH; open storage** 3 months
50-60 °C, ambient RH; open
storage
3 months
** For API1-API2, or API-excipient, or FPP without packing material,
typically a thin layer of material is spread in a Petri dish. Open storage is
recommended, if possible.

13. 3.11.3 Selection of Batches
 At the time of submission data from stability studies should be
provided for batches of the same formulation and dosage form in
the container closure system proposed for marketing.
 Stability data on three primary batches are to be provided. The
composition, batch size, batch number and manufacturing date of
each of the stability batches should be documented and the
certificate of analysis at batch release should be attached.
 Where possible, batches of the FPP should be manufactured by
using different batches of the API.

14. Illustrative data of API stability batches
Batch number
Date of manufacture
Site of manufacture
Batch size (kg)
Primary packing materials
Date of initial analysis
.

15. Illustrative data of capsule/tablet stability
batches
Batch number
Date of manufacture
Site of manufacture
Batch size (kg)
Batch size (number of
units)
Primary packing materials
Date of initial analysis
Batch number of the API

16. photo stability testing
A systematic approach to photostability testing
is recommended covering, as appropriate,
studies such as:
i) Tests on the drug substance;
ii) Tests on the exposed drug product outside of
the immediate pack;
and if necessary ;
iii) Tests on the drug product in the immediate
pack;
and if necessary ;
iv) Tests on the drug product in the marketing
Pack

17. Bracketing and matrixing designs
Bracketing:-As defined in the glossary to the parent
guideline, bracketing is the design of a stability
schedule such that only samples on the extremes of
certain design factors (e.g., strength,
container size and/or fill) are tested at all time points as
in a full design. The design assumes that the stability of
any intermediate levels is represented by the stability of
the extremes tested.

18. Matrixing
As defined in the glossary of the parent guideline, matrixing is
the design of a stability schedule such that a selected subset of
the total number of possible samples for all factor combinations
would be tested at a specified time point. At a subsequent time
point, another subset of samples for all factor combinations
would be tested. The design assumes that the stability of each
subset of samples tested represents the stability of all samples at
a given time point. The differences in the samples for the same
drug product should be identified as, for example, covering
different batches, different strengths, different sizes of the same
container closure system etc

19. STABILITY PROTOCOL AND REPORT
1. Batches tested
2. General information
3. Container/closure system
4. Literature and supporting data
5. Stability-indicating analytical methods
6. Testing plan
7. Test parameters
8. Test results
9. Other requirements (post-approval commitments)
10. Conclusions
Result sheets must bear date and responsible person
signature / QA approval

20. Stability results
 A storage statement should be proposed for the
labeling (if applicable), which should be based on the
stability evaluation of the API.
 A re-test period should be derived from the stability
information, and the approved retest date should be
displayed on the container label.
 An API is considered as stable if it is within the
defined/regulatory specifications when stored at
30±2oC and 65±5% RH for 2 years and at 40±2oC
and 75±5%RH for 6 months.

21. REFERENCES
•Drug Stability: Principles and Practices, 3rd Edition, edited by Jens
T.Carstensen and C. T. Rhodes (Marcel Dekker, Inc., New York, 2000)
•Silke Klick and others: Toward a Generic approach for Stress Testing
of Drug Substances and Drug Products (Pharmaceutical Technology,
February 2005)
•Raphael Bar: Statistical Evaluation of Stability Data: Criteria for
Change-over-time and Data Variability (PDA Journal of
Pharmaceutical Science and Technology, Vol. 57. No.5, Sept./Oct.
2003, pp. 369-377)
•WWW.USFDA.COM