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Stability Studies, Factors influencing stability - Coggle Diagram
Stability Studies
Host of available guidelines in the EU
ICH Q1A (R2) Stability testing of new drug substances and drug products - Scientific guideline
ICH Q1B Photostability testing of new active substances and medicinal products - Scientific guideline
ICH Q1C Stability testing: requirements for new dosage forms - Scientific guideline
ICH Q1D Bracketing and matrixing designs for stability testing of drug substances and drug products - Scientific guideline
ICH Q1E Evaluation of stability data - Scientific guideline
ICH Q1F Stability data package for registration in climatic zones III and IV - Scientific guideline
Declaration of storage conditions for medicinal products particulars and active substances (Annex) - Scientific guideline
In-use stability testing of human medicinal products - Scientific guideline
Maximum shelf-life for sterile products for human use after first opening or following reconstitution - Scientific guideline
Start of shelf-life of the finished dosage form (Annex to the note for guidance on the manufacture of the finished dosage form) - Scientific guideline
Stability testing for applications for variations to marketing authorisation - Scientific guideline
Stability testing of existing active ingredients and related finished products - Scientific guideline
ICH Q6A, Q6B - shelf life specifications
ICH Q3B - specification for degradation
products in a drug product
Other Guidelines
FDA Guidance for the Industry
WHO Annex 5
EMA guidelines - Complications of union procedures on inspections and exchange of information
Food and Drug Administration, USA
International Conference on Harmonization
Pharmaceutical Inspection Convention
European Organization for Quality Control
ICH Q1A (R2) Stability testing of new drug substances and drug products
Stress Testing: Drug products are put under stress from factors such as temperature, humidity and if appropriate oxidation and photolysis for example.
Serves as a stability data package for new drug substances and or products
Container Closure System stability testing: Stability of the drug product is monitored overtime and tested to ensure product quality does not drop. Closure system testing packages must be the same as the proposed packaging for final product.
Seletion of Batches: Data from stability studies of three primary batches must be established within product design space.
Storage Conditions: Drug products should be evaluated under appropriate storage conditions. Thermal stability, moisture sensitivity and solvent loss potential studies should be conducted.
Labelling Statements: Should be direct link between label and demonstrated stability of the product with expiration label affixed/ displayed on container label. Storage requirements should also affixed on the label and link between the stability of product.
Purpose
to evaluate ___ of a drug substance
physical properties
microbiological properties
Chemical properties
Overtime
to determine its shelf life
to ensure its quality
to ensure its efficacy
helps to identify potential
degradation pathways
establish
appropriate storage conditions
support regulatory approval of
the product
Warning Letters and Common Deficiencies
Kari Gran Inc. (NOVEMBER 30, 2022)
21 CFR 211.165(a)
Failed to establish and follow a written testing program
designed to assess the stability characteristics drug products
21 CFR 211.166(a)
failed determine appropriate storage conditions and
expiration dates
Auto-Chlor System LLC (DECEMBER 20, 2022)
21 CFR 211.22
quality control unit failed to exercise its responsibility in ensuring
drug products manufactured meet established specifications
July 19, 2022 Warning Letter served to OTC drug. Inspections were made that showed GMP violations were identified in the area of laboratory testing, stability program, and quality oversight. Main problem areas:
Improper/ Insufficient Stability Programme
Quality Oversight
Lack of proper Laboratory Testing
Bioberica SAU 2022 served warning Letter for failure to do stability tests for 23 reworked API batches in 2020 and 2021, there were no process controls established for the rework steps, which is mandatory to show equivalence of the batches which were produced by reworking compared to the batches of API which were produced by the original validated manufacturing process
Types of Stability Testing
Long Term
Storage Conditions
25C±2C/60%RH ±5%RH
OR 30±2C/65%RH ±5%RH
Minimum Time Period Covered by Data Condition
12 Months
Intermediate
Storage Conditions
40±2C/75%RH ±5%RH
Minimum Time Period Covered by Data Condition
6 Months
Accelerated
Storage Conditions
30±2C/65%RH ±5%RH
Minimum Time Period Covered by Data Condition
6 Months
validation
analytical procedures
limit test fo the control of impurities
quantitative test for impurity content
identification test
robustness
accuracy
recommended data
impurities
assay
drug product
drug substance
range
for drug substance and product- 80-120 test concentrations
for content uniformity-70-130 percent of test concentration
for dissolution testing- +/-20% of the range
for determination of the impurity- 120% range of specification
for toxic and unexpected effect impurities the range should be controlled
precision
intermmediate precision
reproducibility
repeatability
quantitation limit
detection limit
visual examination
signal to noise
quantitative test for impurity content
identification test
calibration of the curve
linearity
Factors influencing stability
Temperature
Changes in temperature can affect the rate of chemical reactions and the physical stability of a drug substance or product.
Humidity
High humidity levels can promote the growth of microorganisms and can cause physical changes such as swelling or caking of the product.
Impurities
The presence of impurities in a drug substance or product can influence its stability and may promote degradation or reactivity.
Packaging
The type of packaging used for a drug substance or product can impact its stability by influencing the exposure to environmental factors such as light, temperature, and humidity.
Composition
The composition of a drug substance or product can influence its stability, with certain combinations of ingredients being more susceptible to degradation or reactivity.
pH
The pH of a drug substance or product can influence its stability and can affect the rate of chemical reactions.