Regulatory Approval | bioequivalence.eu

Regulatory Approval

Approval of Bioequivalence in Pediatrics

Pharmacokinetic and/or clinical studies in children are likely to be required to document bioequivalence. Such studies may be required separately for the age-groups less than two years, 2 – 5 years, 6-12 years and 13-18 years.

LEVEL 1 Regulatory Approval of Bioequivalence (Ref 2)

  • In vitro criteria for equivalence have all been fulfilled
    AND
  • The inhalation device of test product and reference product is similar
    OR
  • The test product is a pMDI without spacer or with a spacer similar to the reference product.

LEVEL 2 Regulatory Approval of Bioequivalence (Ref 2)

  • In vitro criteria for equivalence have all been fulfilled
    AND
  • The reference product is approved in the intended paediatric
    AND
  • the device of the test product is approved in the intende paediatric population containing another active substance.

LEVEL 3 Regulatory Approval of Bioequivalence (Ref 2)

  • In vitro criteria for equivalence have all been fulfilled
    AND
  • Comparative in vitro data which must be provided to demonstrate that the test and reference product produce comparable fine particle performance through the flow rate and pressure drop range and air volume which are clinically applicable to children.
  • A handling study in the relevant age group.

LEVEL 4 Regulatory Approval of Bioequivalence (Ref 2)

  • in vitro criteria for equivalence are not fulfilled
  • The inhalation device of test product and reference product are NOT similar
  • The reference product is NOT approved in the intended paediatric

Requirements:

  • Demonstration of equivalent drug deposition and/or
  • Demonstration of therapeutic equivalence through appropriate pharmacodynamic and/or
  • Demonstration of therapeutic equivalence through appropriate pharmacodynamic clinical studies, and/or
  • Safety data (equivalence based on pharmacokinetic data and measurement of pharmacodynamic parameters

LEVEL 5 Regulatory Approval of Bioequivalence (Ref 2)

If none of the above is fulfilled, equivalent efficacy and safety must be demonstrated: pharmacodynamic and/or clinical efficacy studies:

Bronchodilatation

  • Age 6 years and above: spirometry
  • Age 2-6 years: specific airway resistance as measured by plethysmography combined with clinical symptom scores
  • Age 4-6 years possibly PEF together with clinical symptom scores.

Bronchoprotection

  • Age 6 and above: methacholine challenge or exercise challenge
  • Age 2-6 years: cold air and/or dry air challenge Equivalent safety must also be demonstrated (see the above paragraph).

 

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Professor Hans Bisgaard • Copenhagen • Denmark • Bisgaard@copsac.com