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What kind of studies are required to prove Bioequivalence for new
Generic Inhaler products meant for European Submission?
Pharmacokinetic studies only or Both PK and PD studies Required.?
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You may need to conduct Pharmacokinetic studies and / or Pharmacodynamic studies based on
the results obtained from invitro and Pharmacokinetic studies.
You need to do Pulmonary deposition studies to investigate the extent and pattern of
pulmonary deposition of an inhaled active substance. Pulmonary deposition studies are
designed as double blind, crossover studies and should be carried out using a clinically
relevant dose(s) and strength(s) of the product (which may be determined from the in vitro
data). These studies should be performed in the intended patient population (COPD or
Pulmonary deposition can be investigated by conducting Pharmacokinetic or Imaging studies.
Therapeutic equivalence demonstrated by means of appropriate clinical studies using
well-validated study designs and comparing the test product with the reference product,
becomes mandatory when equivalence is not shown in vitro according to the following
The product contains the same active substance (i.e. same salt, ester, hydrate or solvate,
The pharmaceutical dosage form is identical (e.g. pMDI, non-pressurised MDI, DPI, etc.).
The active substance is in the solid state (powder, suspension): any differences in
crystalline structure and/or polymorphic form should not influence the dissolution
characteristics, the performance of the product or the aerosol particle behaviour.
Any qualitative and/or quantitative differences in excipients should not influence the
performance of the product (e.g. delivered dose uniformity, etc.), aerosol particle
behaviour (e.g. hygroscopic effect, plume dynamic and geometry) and/or be likely to affect
the inhalation behaviour of the patient (e.g. particle size distribution affecting
mouth/throat feel or "cold Freon" effect).
Any qualitative and/or quantitative differences in excipients should not change the safety
profile of the product.
The inhaled volume through the device to enable a sufficient amount of active substance
into the lungs should be similar (within +/- 15%).
Handling of the inhalation devices for the test and the reference products in order to
release the required amount of the active substance should be similar.
The inhalation device has the same resistance to airflow (within +/- 15%).
The target delivered dose should be similar (within +/- 15%)
Pharmacodynamic studies are also required if it is not shown convincingly by investigation
of pulmonary deposition and systemic safety as discussed above.
Head - Clinical Research & Medical Affairs,
Azidus Clinical Research Organization, India
Global Moderator - ClinicalResearchForum
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