Dr_Dan
★★  

2020-02-20 09:01
(281 d 03:34 ago)

Posting: # 21181
Views: 1,304
 

 Orange or citrus flavor [Regulatives / Guidelines]

Dear all
It´s not a question with direct reference to bioequivalence but maybe you have some experience that you can share.
Oral formulations that are a suspension or a solution at time of administration often contain a flavoring agent. In case this is a orange or citrus flavor the German regulatory authority asks whether this flavor contains perilla aldehyd. According to EFSA (European Food Safety Authority) perilla aldehyd contains an α,β-unsaturated carbonyl group, which is a structural alert for toxicity. However, citrus fruits naturally contain perilla aldehyd and if the flavoring agent in your formulation contains natural citrus oil you can not exclude contamination with perilla aldehyd. How can one argue against the authority? Eventually drinking of orange juice is still considered harmless....
Looking forward to your reply.

Kind regards and have a nice day
Dr_Dan
nobody
nothing

2020-02-20 09:18
(281 d 03:17 ago)

@ Dr_Dan
Posting: # 21182
Views: 884
 

 Orange or citrus flavor

Hi!

IMHO: whenever it comes to questions like this, prepare a careful and extensive reflection on the quantitative aspects of exposure. Don't forget that pharmaceuticals are add-on exposure to natural/dietary exposure...


Edit: Please don’t shout[Helmut]

Kindest regards, nobody
ElMaestro
★★★

Belgium?,
2020-02-20 09:41
(281 d 02:54 ago)

@ Dr_Dan
Posting: # 21183
Views: 872
 

 Orange or citrus flavor

Hi Dr_Dan,


it is a tricky question. On whom is the burden of proof here?

I would perhaps try and argue that since the excipient is common, used for decades, generally allowed and since PRAC and CHMP and SWP and so forth did not in any way indicate the need for a review of safety/potential toxicity etc., the excipient should be considered ok.
At the end of the day the purpose of the regulatory mechanisms is to capture those things since they have access to much more info then you/we have. Their analysis is potentially much more sensitive than anything you can look into or speculate into.

Absence of evidence vs evidence of absence...

I could be wrong, but...

Best regards,
ElMaestro

No, of course you do not need to audit your CRO if it was inspected in 1968 by the agency of Crabongostan.
nobody
nothing

2020-02-20 12:24
(281 d 00:11 ago)

@ ElMaestro
Posting: # 21184
Views: 861
 

 Orange or citrus flavor

» it is a tricky question. On whom is the burden of proof here?

As always, when the authority asks: On you... :-D

Kindest regards, nobody
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