- All > Quality and Safety: Medicines > Quality Assurance
- All > Quality and Safety: Medicines > Safety and Efficacy
(2007; 26 pages)
Adequate evidence/proof of efficacy and safety for all multisource products in the form of appropriate in vivo bioequivalence studies should be submitted with each (except biological) application for the registration of a medicine.
To exert an optimal therapeutic action, an active moiety should be delivered to its site of action in an effective concentration for the desired period. To allow reliable prediction of the therapeutic effect, the characteristics of the dosage form containing the API, should be well defined.
Comparison of the therapeutic performances of two pharmaceutical products containing the same API is a critical means of assessing the possibility of using either the innovator, or a multisource (generic) pharmaceutical product. Assuming that in the same subject a similar plasma drug concentration time course will result in similar drug concentrations at the site of action and thus in a similar effect, pharmacokinetic data instead of therapeutic results may be used to establish bioequivalence.
The objectives of this guideline are to:
a) Define when bioavailability or bioequivalence data will be required in order to prove safety and efficacy.
b) Provide guidance on the design and conduct of studies and the evaluation of data.
c) Provide guidance when in vitro instead of in vivo data may be used.
d) Provide guidance when suitably validated pharmacodynamic methods can be used to demonstrate bioequivalence.
For pharmaceutical products, where the active ingredient is not intended to be delivered into the general circulation, the common systemic bioavailability approach cannot be applied. Under these conditions availability (local) may be assessed by quantitative measurements which appropriately reflect the presence of the active ingredient at the site of action.
This guideline represents the current thinking on this subject. It does not create or confer any rights for or on any person and does not operate to bind the SADC medicine regulatory authorities or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations in the member states.
The guideline addresses how to meet the BA and BE requirements as they apply to dosage forms intended for oral administration. It is also generally applicable to non-orally administered medicine products where reliance on systemic exposure measures is suitable to document BA and BE (e.g., transdermal delivery systems and certain rectal and nasal medicine products). It should be useful for applicants planning to conduct BA and BE studies during the investigational period for a new medicine application, BE studies intended for submission in multisource medicine applications, and BE studies conducted in the post-approval period for certain changes in both new medicine applications and multisource medicine applications...