highest dose ⇔ strength for dummies [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2017-05-10 18:28 (2514 d 23:27 ago) – Posting: # 17348
Views: 9,583

Dear Detlew,

❝ ❝ Example phenytoin: Nonlinear PK (greater than proportional increase in AUC), NTID. Highest strength 100 mg (studies for the EMA). Highest approved therapeutic dose 3×100 mg (studies for the FDA).


❝ If somebody creates a 300 mg tablet / capsule ... whatever, then highest strength is 300 mg :confused:.


Not easy. First of all, what is the reference? For the EMA it is the product which was approved based on a complete dossier (acc. to article 8(3), 10a, 10b or 10c of 2001/83/EC). Say the highest strength was 100 mg and up to 300 mg were used in phase III. Hence, the innovator can develop a new 300 mg strength and get it approved in a line extension (only BE studies 300 mg vs. 3×100 mg).

Tricky for a 300 mg strength not developed by the originator:
  1. Highest strength of the innovator still 100 mg. Hybrid application (acc. to 8(3) of 2001/83/EC): Comparative BA 300 mg vs. 3×100 mg plus clinical studies.
  2. Highest strength of the innovator already 300 mg. Strictly speaking this product was not approved based on a complete dossier (but a line extension). IMHO, you cannot apply for a purely generic application (300 mg vs. 300 mg). Is case (a) applicable? Duno. Ask a lawyer and go for a scientific regulatory advice.
For the FDA at least the selection of the reference is somewhat easier: “RLD is what we decide to be the RLD. Full stop.” Look it up Drugs@FDA. If the originator gets a new 300 mg approved, the FDA might list this strength as the new RLD or decide to keep the 100 mg as the RLD…

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,636 registered users;
97 visitors (0 registered, 97 guests [including 7 identified bots]).
Forum time: 16:56 CET (Europe/Vienna)

With four parameters I can fit an elephant,
and with five I can make him wiggle his trunk.    John von Neumann

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5