Exploring the Feasibility of a Bracketing Approach Utilizing Modeling for Development of Long-Acting Injectables for Regulatory Approval—A Case Study Using Levonorgestrel
2024

Bracketing Approach for Long-Acting Contraceptives

publication Evidence: moderate

Author Information

Author(s): Cole Susan, Pertinez Henry, Butler Andrew S., Kerwash Essam, Bhat Swati, El-Khateeb Eman, Owen Andrew

Primary Institution: Medicines and Healthcare Products Regulatory Agency, UK

Hypothesis

Can a bracketing approach utilizing modeling support the development of long-acting injectables for regulatory approval?

Conclusion

The current understanding of exposure response is insufficient to support a bracketing approach for a new levonorgestrel product without additional safety data.

Supporting Evidence

  • The study suggests that a bracketing approach could reduce the time and cost of developing new long-acting contraceptives.
  • Current regulations may allow for reduced application packages if additional safety data are established.
  • Levonorgestrel's target concentrations for efficacy are defined between 200–400 pg/mL.

Takeaway

This study looks at how to use existing data to help create new long-lasting contraceptives more quickly and cheaply.

Methodology

The study utilized literature evidence of levonorgestrel efficacy and safety, modeled data, and reviewed regulatory databases.

Potential Biases

Potential biases in real-world data due to reporting and publication issues.

Limitations

The concentration-response profiles are sparse and variable, making it challenging to define safety brackets.

Digital Object Identifier (DOI)

10.3390/ph17121640

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