Perfiles de disolución - Parte 5 - Factor de diferencia F1

Key Concepts

• F1 Factor of Difference: A measure of the percentage difference between two dissolution curves, used to determine if two drug products are interchangeable.
• Dissolution Profile: A graphical representation of the rate at which a drug dissolves over time.
• Reference (R): The original or innovator drug product.
• Test (T): The generic or alternative drug product being compared to the reference.
• Interchangeability: The ability of a generic drug product to be substituted for the reference drug product.
• Norma Oficial Mexicana 177: The Mexican regulatory standard for dissolution testing.
• FDA Method: The dissolution testing method used in the United States, as defined by the Food and Drug Administration.
• Efficiency: A measure of the overall dissolution performance of a drug product.
• Mean Dissolution Time: The average time it takes for a drug product to dissolve.

F1 Factor of Difference: Introduction

The video discusses the F1 factor of difference, a test used to compare dissolution profiles of different drug products. It builds upon a previous video that explained the FDA method and the Norma Oficial Mexicana 177 for dissolution testing, highlighting the differences in these regulatory approaches. The speaker emphasizes the importance of understanding both methods, especially for professionals working in different countries.

F1 Factor of Difference: Definition and Significance

The F1 factor of difference is defined as the percentage difference between two dissolution curves. Specifically, it's a measure of the relative error between the dissolution profile of a reference product (R) and a test product (T).

• Acceptance Criteria: An F1 value between 0 and 15 indicates that there are no significant differences between the dissolution profiles, suggesting the two products are interchangeable.

F1 Factor of Difference: Calculation (Norma Oficial Mexicana 177)

The speaker demonstrates the calculation of the F1 factor using the Norma Oficial Mexicana 177 method with a specific example.

• Formula: F1 = (Sum of |R - T| / Sum of R) * 100
• Step 1: Create a table with time points, the amount of drug dissolved for the reference product (R), and the amount of drug dissolved for the test product (T).
• Step 2: Calculate the difference between R and T at each time point (R - T). Take the absolute value of each difference.
• Step 3: Sum the absolute differences calculated in Step 2 (Sum of |R - T|).
• Step 4: Sum the values of R (Sum of R).
• Step 5: Apply the formula: F1 = (Sum of |R - T| / Sum of R) * 100.
• Important Note: The Norma Oficial Mexicana 177 requires the test to be conducted until the reference product (R) reaches 85% dissolution, plus one additional time point. Data beyond this point is not considered for the F1 calculation.
• Example:
  • Sum of |R - T| = 194
  • Sum of R = 759
  • F1 = (194 / 759) * 100 = 25.5

F1 Factor of Difference: Interpretation (Norma Oficial Mexicana 177)

The calculated F1 value is then interpreted based on the acceptance criteria.

• Result: In the example, the F1 value is 25.5.
• Conclusion: Since 25.5 is greater than 15, there are significant differences between the dissolution profiles of the reference and test products. Therefore, the test product is not considered interchangeable with the reference product according to the Norma Oficial Mexicana 177.

F1 Factor of Difference: Calculation (FDA Method)

The speaker then calculates the F1 factor using the FDA method, using the same data but extending the time points considered.

• Key Difference: The FDA method requires both the reference (R) and test (T) products to reach 85% dissolution, plus one additional time point. This often results in more data points being included in the calculation compared to the Norma Oficial Mexicana 177.
• Calculation: The same formula (F1 = (Sum of |R - T| / Sum of R) * 100) is used, but with different summation values due to the inclusion of more time points.
• Example:
  • Sum of |R - T| = 237
  • Sum of R = 1348
  • F1 = (237 / 1348) * 100 = 17.5

F1 Factor of Difference: Interpretation (FDA Method)

The F1 value calculated using the FDA method is also interpreted based on the 0-15 acceptance range.

• Result: In this case, the F1 value is 17.5.
• Conclusion: Since 17.5 is greater than 15, there are significant differences between the dissolution profiles, and the test product is not considered interchangeable with the reference product according to the FDA method.

Implications and Conclusion

The speaker emphasizes the implications of failing the F1 test.

• Impact on Interchangeability: The test product (T), which is seeking approval as an interchangeable generic drug, fails the F1 test under both the Norma Oficial Mexicana 177 and FDA methods.
• Need for Reformulation: This suggests that the test product may need to be reformulated to achieve a dissolution profile that is sufficiently similar to the reference product to be considered interchangeable.
• F1 as a Screening Tool: The F1 test serves as an initial screening tool to determine if a generic drug product has a reasonable chance of being bioequivalent to the reference drug.
• Bioequivalence is Key: A drug is only truly interchangeable if it is bioequivalent, and the F1 test provides a range of up to 15% difference while still considering the products interchangeable.

The video concludes by noting that the F1 test is just one of several tests required to establish interchangeability and that the next video will cover another such test. The speaker also summarizes the results obtained so far, including the efficiency and mean dissolution time, highlighting the differences between the reference and test products.