Drugdu.com expert's response:

The drug stability influencing factors test is a critical study that evaluates the quality changes of drugs under specific environmental conditions, aiming to provide a scientific basis for drug formulation design, packaging selection, storage condition determination, and expiry date setting. Its core considerations cover various aspects, including test design, condition control, sample management, testing and analysis, as well as data recording and reporting, as detailed below:

I. Test Design Phase

Clarify Test Objectives: Distinguish between influencing factors tests (e.g., high temperature, high humidity, intense light) and long-term stability tests or accelerated tests, clarifying the focus of each test (e.g., rapid screening of degradation pathways vs. prediction of long-term stability). Design targeted test protocols based on drug characteristics (e.g., chemical structure, dosage form, pH sensitivity).

Select Representative Samples: Use samples (including both active pharmaceutical ingredients and formulations) that are consistent with actual production batch processes, avoiding laboratory-scale pilot samples. Ensure that sample packaging is consistent with the final marketed packaging to assess the impact of packaging on stability.

Set Scientifically Reasonable Test Conditions: High-temperature test: Typically, temperatures such as 40°C and 60°C are selected to cover extreme storage or transportation conditions that drugs may encounter. High-humidity test: Relative humidity (RH) is generally set at 75% ± 5% or 90% ± 5%, considering the drug's hygroscopicity. Intense light test: Use a total illuminance of not less than 1.2 × 10⁶ Lux·h (near-ultraviolet lamp) or 500 W·h/m² (visible light) to simulate the environment of drug exposure to light. Other conditions: Depending on drug characteristics, special condition tests such as freeze-thaw cycles, oxidation, and acid-base conditions may be added.

II. Test Execution Phase

Strict Condition Control: Utilize calibrated equipment such as constant temperature and humidity chambers and light exposure chambers to ensure that temperature, humidity, and light intensity comply with set values. Regularly monitor and record environmental parameters to avoid temperature fluctuations or humidity deviations that may affect results.

Sample Placement and Sampling: Placement method: Samples should be laid flat or suspended in petri dishes to avoid uneven heating or light exposure due to stacking. Sampling time points: Set sampling intervals (e.g., 0, 5, 10 days) based on the drug's degradation rate to ensure capture of key degradation stages. Sampling quantity: Ensure that the quantity sampled meets the needs of all testing items while avoiding frequent sampling that may compromise sample integrity.

Avoid Cross-Contamination: Strictly isolate different test conditions or different drug samples to prevent interference from volatile components or degradation products.

III. Testing and Analysis Phase

Comprehensive Testing Items: Include physical properties (appearance, color, odor), content, related substances (degradation products), dissolution, moisture content, pH value, etc. Add specific tests based on drug characteristics (e.g., sterility testing for sterile formulations, aggregate analysis for protein drugs).

Method Validation: Ensure that testing methods (e.g., HPLC, GC, UV) meet requirements for specificity, sensitivity, accuracy, and precision. Validate method separation for degradation products using forced degradation tests (e.g., acid, base, oxidation, pyrolysis).

Timely Data Analysis: Compare testing results between initial and post-test samples, calculate degradation rates, and plot degradation curves. Identify major degradation pathways (e.g., hydrolysis, oxidation, photolysis) to provide a basis for formulation process optimization.

IV.Data Recording and Reporting

Complete Documentation of the Test Process: Record test conditions (temperature, humidity, light intensity), sample information, sampling times, testing methods, and results in detail. Retain original data (e.g., chromatograms, spectra) and explanations for any anomalies (e.g., equipment failures, power outages).

Scientific Interpretation of Results: Analyze degradation mechanisms in conjunction with drug chemical properties and assess the necessity of packaging materials (e.g., light-blocking packaging, desiccants). Determine drug storage conditions (e.g., "Store in a cool, dry place protected from light") and expiry dates based on test results.

Compliance Reporting: Write test reports in accordance with ICH guidelines (e.g., Q1A) or requirements from various pharmacopoeias, ensuring completeness and logical clarity of content.

V. Special Considerations

Stability of Biological Products: Pay additional attention to indicators such as protein aggregation, virus inactivation verification, and cell viability. Evaluate the impact of water activity on the stability of freeze-dried products.

Stability of Multi-Dose Packaging: Simulate actual use scenarios (e.g., after repeated opening) to assess the stability of drugs after unsealing.

Transportation Simulation Tests: Design transportation simulation tests incorporating vibration, impact, and temperature cycling based on the results of influencing factors tests to ensure drug quality during logistics. By strictly adhering to the above considerations, the scientific validity, reliability, and compliance of drug stability influencing factors tests can be ensured, providing a solid quality assurance foundation for drug development and market approval.