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  • Regulatory Requirement for Stability Study

    A pharmaceutical product’s shelf-life estimation by assessing through a systematic stability study is a regulatory requirement, during this review current regulatory requirements are elaborated.

    The main aim of this study is to produce an indication of how the drug substance and drug product quality change with time by exposure to different climate conditions like temperature, humidity, and photolytic condition. A stability study helps to establish a retest period for the drug substance and validity of the drug product and proposed storage conditions and proves that it meets its set specifications.

    What is Stability?

    Stability defines as, “The formulated products remains stable during its period within its physical, chemical, microbiological, pharmacological and medicinal specification in its designated packaging state”. A stability study is a vital requirement to prove the safety and efficacy of pharmaceutical drug substances and drug products.

    Factors Affecting Stability of Drug Substances and Drug Products:

    Due to following physical or chemical variations forms in drug substances and drug products resulted in the degradation and subsequently reduction of assay or potency and formation of impurities.

    1. Oxidation/Reduction reaction
    2. Moisture content
    3. Temperature
    4. pH
    5. Hydrolysis
    6. Light
    7. Concentration of drug
    8. Particle size
    9. Package integrity

    Different Stages and Kinds of Stability Studies:

    Different Stages of Stability Studies: Following are the various stages of stability studies performed from the various stages of formulation development to the registration of drug substances or drug products. Each stage of formulation development ensures to satisfy the set specification up to the proposed period of its shelf life.

    1. Drug substance stability study,
    2. Formulation development study batches stability study,
    3. Scale up batch/Preclinical and Clinical study batches stability study,
    4. Exhibit batches or Registration batches stability study,
    5. Commercial or Marketed products stability study

    Different Kinds of Stability Studies: Following are the various kinds of stability studies that were performed which are mainly of 4 types:

    1. Long-term stability study,
    2. Intermediate stability study,
    3. Accelerated stability study,
    4. In-use stability study.

    Stability Study Protocol:

    The stability study protocol is the most significant document to stipulate the activities to be applied during stability studies. The stability study protocol illustrates the following details:

    1. Specification
    2. Standard test procedure
    3. Batch details
    4. Packaging details
    5. Sampling time points

    Different Zone for Stability Study Testing:

    The world is divided into 4 different geographical zones on the basis of climate and pharmaceutical drug products probably exposed during their storage condition. The storage conditions were obtained on the basis of average yearly temperature and relative humidity.    

    ZoneClimate TypeTemperature/Humidity (Long Term Condition)Temperature/Humidity (Accelerated Condition)
    Zone IModerate Zone21° ± 2°C/45%RH ± 5%RH40° ± 2°C/75%RH ± 5%RH
    Zone IIMediterranean/Subtropical25° ± 2°C/60%RH ± 5%RH40° ± 2°C/75%RH ± 5%RH
    Zone IIIHot Dry Zone30° ± 2°C/35%RH ± 5%RH40° ± 2°C/75%RH ± 5%RH
    Zone IVaHot Humid/Tropical Zone30° ± 2°C/65%RH ± 5%RH40° ± 2°C/75%RH ± 5%RH
    Zone IVbHot/Higher Humidity30° ± 2°C/75%RH ± 5%RH40° ± 2°C/75%RH ± 5%RH
    CoolRefrigerated5° ± 3°C/No Humidity25° ± 2°C/60%RH ± 5%RH
    ColdestFrozen– 15° ± 5°C/No Humidity5° ± 3°C/ No Humidity

    The main target of the study is to prove how the drug substance or drug product behaves during its storage under various temperature and humidity conditions. As per the regulatory requirement of stability, the results obtained of drug substances and drug products demonstrate that the identity, strength, efficacy, and quality are unchanged during their storage condition as per the set specifications.


    1. U.S.FDA, Title 21 of the U.S. Code of Federal Regulations.21 CFR 211-Current Good Manufacturing for Finished Pharmaceuticals,
    2. ICH, Q1A (R2) Stability Testing in New Drugs and Products,
    3. ICH, Q1B Photo-Stability Testing of New Drug Substances and Products,
    4. ICH, Q1C Stability testing of New Dosage Forms,
    5. ICH, Q1D Bracketing and Matrixing Designs for Stability Testing of Drug Substances and Drug Products,
    6. ICH, Q1E Evaluation of Stability Data,
    7. ICH, Q1F Stability Data Package for Registration in Climatic Zones III and IV,
    8. ICH, Q5C Quality of Biotechnological Products: Stability testing of Biotechnological/Biological Products,
    9. R.G. Hill and H.P. Rang, Eds., Drug Discovery and Development: Technology in Transition (Churchill Livingston, Elsevier, Edinburgh, Scotland, 2nd Ed., 2012),
    10. K. Huynh-Ba, Ed., Handbook of Stability Testing of Pharmaceutical Products: Regulations, Methodologies and Best Practices (Springer, New York, 2009),
    11. K. Waterman, Understanding and Predicting Pharmaceutical product Shelf life, In Handbook of Stability Testing of Pharmaceutical Products: Regulations, Methodologies and Best Practices (Springer, New York, 2009),
    12. WHO Expert Committee on Specifications for Pharmaceutical Preparations Fifty-second report, annex 10, Stability testing of active pharmaceutical ingredients and finished pharmaceutical products (World Health Organization, 2018).

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