Bioequivalence and Bioavailability Forum • clinical trials/ BE studies for locally acting drugs

jagankm
☆

2012-01-25 12:26
(5251 d 10:31 ago)

Posting: # 7999
Views: 7,200

clinical trials/ BE studies for locally acting drugs [Regulatives / Guidelines]

Dear Sir/ Madam,

Here we have a query regarding clinical studies of generic products for UK market (Bioequivalence studies). We are developing following generic drug products for UK market:

Docusate sodium 100mg soft gelatin capsules
Sulfasalazine Gastro-resistant Tablets 500 mg

Since both the above drugs are locally acting in gastro intestinal tract. As per the guidelines (CPMP/EWP/QWP/1401/98 Rev. 1/ Corr *, CPMP/EWP/239/95 final), bioequivalence is not a suitable way to show therapeutic equivalence between two products. Could you give a suggestion in showing these two products bioequivalent to innovator products. And is it possible for biowaiver for both the above drug products or any other clinical studies to be conducted to show bioequivalent for these drug products.

Your kind help highly appreciated.

drgunasakaran1
★★

2012-01-31 19:42
(5245 d 03:15 ago)

@ jagankm
Posting: # 8033
Views: 6,263

clinical trials/ BE studies for locally acting drugs

Post reply

Dear Mr.Jegankm,

You need to conduct single dose, two way, cross over invivo study to show bioequivalence for Sulfasalazine Gastro-resistant Tablets 500 mg.
Since, the concentration obtained after the oral administration of Sulfasalazine 500 mg tablets will be too low due to minimal systemic absorption, it is permissible to administer more than one 500 mg tablets (upto four 500 mg tablets) to obtain adequate plasma concentration for the pharmacokinetic analytes (Sulfasalazine, and the metabolites sulfapyridine and 5-Aminosalicylic -ASA) acid (mesalamine) in plasma.

Bioequivalence will be based on Sulfasalazine as well as 5-Aminosalicylic acid.

For Docusate sodium 100mg soft gelatin capsules, it is preferable to conduct a Pharmacodynamic study.

—
Dr Gunasakaran Sambandan MD
Disclaimer: The replies/posts are my personal opinions, and they do not represent my company's views on the same. LinkedIn

Ohlbe ★★★ France, 2012-01-31 20:01 (5245 d 02:56 ago) @ drgunasakaran1 Posting: # 8034 Views: 6,180	clinical trials/ BE studies for locally acting drugs Post reply
	Dear Dr Gunasakaran Any reference to support your recommendation, including regarding metabolites ? Remember the query is for EU submission, not FDA. Regards Ohlbe — Regards Ohlbe

jagankm ☆ 2012-02-06 13:00 (5239 d 09:57 ago) @ Ohlbe Posting: # 8056 Views: 6,241	clinical trials/ BE studies for locally acting drugs Post reply
	thank you for your response. as per US FDA guidlines we have to conduct two BE studies both in fasting and fed conditions for sulfasalazine. but we are in ambiguity to show BE for this molecule. for docusate sodium, it is a solution in soft gelatin capsuls, as per the EMEA guidlines on locally acting liquids we may go for biowaivers.

Tina ★ India, 2013-09-16 20:10 (4651 d 03:47 ago) @ jagankm Posting: # 11502 Views: 5,346	clinical trials/ BE studies for locally acting drugs Post reply
	Dear jagankm, How can liquid filled capsule be taken as a locally acting liquid? Dr. Gunasakaran is suggesting a pharmacodynamic study. Do we require one? If yes, how will the study be conducted? Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut]

Tina ★ India, 2013-09-19 11:45 (4648 d 12:11 ago) @ drgunasakaran1 Posting: # 11521 Views: 5,320	clinical trials/ BE studies for locally acting drugs Post reply
	Dear Dr. Gumasakaran, Could you elaborate on the pharmacodynamic study for Docusate sodium please? Will this product be not applicable for a biowaiver? Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]