Bioequivalence and Bioavailability Forum

Dear all,


Anyone gone through the EMA response to comments on Tadalafil?

As per EMA “GUIDELINE ON THE INVESTIGATION OF BIOEQUIVALENCE” it is mentioned as “In general, a bioequivalence study should be conducted under fasting conditions as this is considered to be the most sensitive condition to detect a potential difference between formulations...... However, for products with specific formulation characteristics (e.g. microemulsions, solid dispersions), bioequivalence studies performed under both fasted and fed conditions are required unless the product must be taken only in the fasted state or only in the fed state."

In draft product specific BE guidance for Tadalafil Tablets it was mentioned that “The reference product is considered to have specific formulation characteristics to enhance the rate of absorption of the drug and therefore, it cannot be assumed that the impact of food will be the same regardless of formulation. The product can be taken without regard to food. Thus, both fasted and fed state comparisons of test to reference formulations are required."


There were several comments submitted to EMA on the above mentioned point quoting that the “Cialis contains conventional excipients. There are no special ingredients, matrix formation or solubility enhancers, except for the commonly used wetting agent – sodium lauryl sulfate (SLS) and the formulation was prepared using conventional wet granulation process. Apart from this Cialis SmPC recommends intake of the reference medicinal product on an empty stomach or irrespective of food intake. So looking into all this only fasting study should be required.”


To this the response from EMA is “If the generic is manufactured using the same technology and similar formulas as the originator it may be justifiable to deviate from the guidance by avoiding the fed study.”


Same technology and similar formulas as originator!! Seriously?


Are there chances that the same requirement can be extended to other products (where a surfactant has been added/micronized API used and/or some specific technology used for originators) whenever the new set of BE guidance will be available?


Life is tough!!!!