ich guidelines of stability ppt
TRANSCRIPT
Ich guidelines for Stability
CONTENTS
INTRODUCTION
STRUCTURAL FEATURES OF ICH GUIDELINES FOR STABILITY
PREDICTION OF SHELF LIFE
PARAMETERS EVALUATED
ICH
“International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use”
ICH is a joint initiative involving both regulators and research-based industry representatives of the European Union, Japan and the USA in scientific and technical discussions of the testing procedures required to assess and ensure the safety, quality and efficacy of medicines.
Objective of ICH
To increase international harmonisation of technical requirements to ensure the safe, effective, and high quality medicines
Developement and registration of these drugs in the most efficient and cost-effective manner
Prevent unnecessary duplication of clinical trials in humans
To promote public health
Minimize the use of animal testing without compromising safety and effectiveness
Make information available on ICH, ICH activities and ICH guidelines to any country or company that requests the information
Promote harmonisation processes related to ICH guidelines regionally and globally
To strengthen the capacity of drug regulatory authorities and industry to utilise them.
STABILITY The capacity of a drug substance or drug product to remain within the established specifications to maintain its identity, strength, quality and purity through out the retest or expiration dating period.
NEED OF STABILITY STUDIES# To determine the shelf life# To determine quality, safety and efficacy of a drug product.
GLOBAL CLIMATIC ZONES
ZONES(CONDITION)
MEAN KINETIC TEMPERATURE
AVERAGE YEARLY % RH
ZONE I(Moderate)
21 45
ZONE II(Mediterranian)
25 60
ZONE III(Hot, Dry)
30 35
ZONE IV(Very hot, Moist)
30 70
PREDICTION OF SHELF LIFE
SHELF LIFE :- The time during which the dosage form is supposed to
retain its original qualities.
STEPS INVOLVED IN PREDICTION OF SHELF LIFE :-
1. Division of formulation and storage at different elevated temperatures like 400C, 500C, 600C and 700C to accelerate degradation.
2. Withdrawal of samples at various intervals of time and measurement of remaining concentration of active ingredients
3. Determination of order of reaction
4. Calculation of reaction rate constant K for the degradation at each elevated temperature.
5. Determination of K at room temperature from linear plot of log K values at different elevated temperatures against the reciprocal of absolute temperature
6. Extrapolation of curve to 25 0C and obtain K value at 250C
7. Substitution of K value in appropriate rate equation and shelf life is estimated
8. Calculation for determination of overage
GENERAL STRUCTURAL FEATURES OF ICH GUIDELINES FOR STABILITY
SELECTION OF BATCHESCONTAINER AND CLOSURE SYSTEMTESTING FREQUENCYFor long-term studies – every 3 months over the first year every 6 months over the second year annually thereafter through the proposed re-test
period.
for accelerated storage condition - minimum of three time points, including the initial
and final time points (e.g., 0, 3, and 6 months), from a 6-month study
for intermediate storage condition - four time points, including the
initial and final time points (e.g., 0, 6, 9, 12 months), from a 12-month study
STORAGE CONDITIONS:-
Study Storage condition Minimum time period covered bydata at submission
Long term* 25°C ± 2°C/60% RH ± 5% RHor30°C ± 2°C/65% RH ± 5% RH
12 months
Intermediate** 30°C ± 2°C/65% RH ± 5% RH 6 months
Accelerated 40°C ± 2°C/75% RH ± 5% RH 6 months
*studies are performed at 25 ±2°C/60% RH ± 5% RH or 30°C ± 2°C/65% RH ± 5% RH.
** If 30°C ± 2°C/65% RH ± 5% RH is the long-term condition, there is no intermediate condition.
Drug substances intended for storage in a refrigerator
Study Storage condition Minimum time period covered bydata at submission
Long term 5°C ± 3°C 12 months
Accelerated 25°C ± 2°C/60% RH ± 5% RH
6 months
Long term** - 20°C ± 5°C 12 months
*FOR STORAGE IN FREEZER
EVALUATION
PHYSICAL TEST
CHEMICAL TEST BIOLOGICAL TEST
MICROBIOLOGICAL TEST
GENERAL PARAMETERS EVALUATED APPEARANCE
PHYSICAL PARAMETERS
CHEMICAL PARAMETERS
- MOISTURE CONTENT - OXYGEN CONSUMPTION
DRUG CONTENT
pH
PARAMETERS EVALUATED FOR DIFFERENT DOSAGE FORMS
Tablets :-
• Dissolution (or disintegration, if justified)
• Water content
• Hardness/Friability
• Tests for texture and colour stability (For coated and coloured tablets)
Capsules :-
• Brittleness
• dissolution (or disintegration, if justified)
• water content
• level of microbial contamination
Emulsions :-
• Phase separation
• pH
• Viscosity
• Level of microbial contamination
• Mean size
• Distribution of dispersed globules
Oral solutions and suspensions :-
• Formation of precipitate• clarity for solutions• pH• Viscosity• Extractables• level of microbial contamination • Redispersibility• rheological properties• mean size• distribution of particles • polymorphic conversion (if applicable)
Nasal sprays: solutions and suspensions :-
• Clarity (for solution)• level of microbial contamination• pH• particulate matter• unit spray medication content uniformity• number of actuations meeting unit spray content
uniformity per container• droplet and/or particle size distribution• weight loss• pump delivery• microscopic evaluation (for suspensions)• foreign particulate matter extractable/leachable from
plastic and elastomeric components of the container, closure andpump.
Powders and granules for oral solution or suspension :-
• Water content• Reconstitution time
Suppositories :-
• Softening range• Dissolution (at 37°C).
Topical, ophthalmic and otic preparations :-
• Clarity• Homogeneity• pH• resuspendability (for lotions)• Consistency• Viscosity• particle size distribution (for suspensions
when feasible) • level of microbial contamination/sterility• weight loss (when appropriate).
Cutaneous sprays :-
• pressure• weight loss• net weight dispensed• delivery rate• level of microbial contamination• spray pattern• water content• particle size distribution (for suspensions)..
Parenterals :-
• Colour• clarity (for solutions)• particulate matter• pH• Sterility• Endotoxins• Volume*
REFERENCES
1. Sinko patrick J, “Martin’s Physical Pharmacy & Pharmaceutical Sciences”, published by Waulters kluwer health (India) pvt ltd, New Delhi, 5th edition, 2006
2. www.ema.europa.eu /docs.
THANKS