Generic product of fixed dose combination product [Regulatives / Guidelines]

posted by varun9461 – India, 2017-11-30 12:03 (2417 d 15:57 ago) – Posting: # 18026
Views: 4,832

Dear All,

We seek further clarity on this topic,

As per post of Shuanghe, new guideline has an additional requirement of demonstration FDC BE against the individual subtances, this could be done by following options

option 01

1. TAB vs RAB as usual, and
2. RAB vs (RA + RB)- evidence based approach

option 02

1. TAB vs RAB as usual, and
2. TAB vs (RA + RB)

But if we refer section 4.6. Bridging the evidence base to the fixed combination medicinal product
Clinical data establishing the contribution of each active substance and the positive benefit-risk are often obtained from the combined use of individual active substances. In this case demonstration of similar pharmacokinetics (usually through demonstrating bioequivalence) of the fixed combination medicinal product versus its individual active substances taken simultaneously is required. This is to satisfy the third basic requirement for an MAA for fixed combination medicinal products. An efficient study design is to compare AB versus concurrent administration of A and B as individual active substance products, in which case bioequivalence can be evaluated for each active substance separately considering individual active substance product characteristics characteristics; e.g. highly variable drug, narrow therapeutic index, biopharmaceutics classification system (BCS) classification, appropriate sampling schedule, and release mechanism (requirements differ for immediate- and modified-release products).

If we refer above paragraph from the guideline, then is it concluding to prove BE of FDC as follows

1. TAB vs RAB as usual, and
2. TAB vs (RA + RB)


Can we do BE of FDC as TAB vs RAB, and provide evidence base data for RAB vs (RA + RB) from innovator published studies or PAR or scientific discussion to support to clinical dossier.


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