Aside from any perceived issues about the NDA treatment of the evidence submitted in the article 13.1 dossier, the companies were must frustrated, Martinho said, by the change in claim wording instigated by the NDA, with no consultation with the relevant parties after the dossier was resubmitted in September last year.
See through the fog?
“This brings a fog over the whole sector,” Martinho said. “Our claims were exactly the same as the claims approved in France eight years ago and were about oxidation and lutein and the retina. But the NDA changed the claim to 'maintains normal vision' without any consultation.”
“We have tried all channels to contact them to try and understand this but have had no success at all. Is this a mistake? We need to know why they have done this before we make any move forward with any new file. But we will see what the European Community does with these opinions now.”
The NDA did a similar thing when it twice rejected lutein dossiers referencing more than 200 studies in 2009 and 2011, even though specific lutein eye health claims had been approved by the French Food Safety Agency (ANSES) in 2004.
Those claims, which remain valid in France until six months after any claim rejection is written into EU lawboooks, are:
·
“Lutein helps protect the retina and the lens from oxidation”
· “Lutein is one (of the) constituent(s) of the retina and the lens”
While Canada and Brazil have also backed its eye health-boosting properties, the US Food and Drug Administration (FDA) turned it down in, also in 2004, citing a lack of surrogate endpoints or biomarkers to validate an age-related macular degeneration (AMD) claim as a major weakness among a Cognis (now part of BASF) submission that included 12 intervention trials.
BASF Nutrition and other major suppliers like OmniActive Health Technologies did not respond to comment requests by the time of publication.
Martinho said DSM and Kemin had begun to strengthen ties with lutein researchers even before the opinion came through.
“It doesn’t change that much to our business as we have been working with different stakeholders in the research community and looking to strengthen our connections there.”
NDA can’t see an effect
The lutein sector was pinning its hopes on the main addition in the resubmission - a study (LUXEA) of zeaxanthin and lutein supplements, and their accumulation in the eye.
But in dismissing it, the NDA observed, “that the visual performance study was not randomised, that no information was provided on how subjects were selected from the LUXEA study, that the statistical methods used for data analysis are poorly described in the publications, and that no information is provided about the baseline characteristics of the subjects for the variables of interest, or about their comparability between groups.”
“The Panel also notes that the final sample size analysed for visual performance outcomes is small, and that the study was likely to be underpowered for such outcomes. The Panel considers that no conclusions can be drawn from the study reported in these two publications for the scientific substantiation of the claim.”
It affirmed that, “the predictive value of changes in macular pigment optical density as an indicator of improved vision has not been established.”
In dismissing in vitro and ex vivo studies, it said, “lutein can act as a free radical scavenger in vitro.” But that did not establish, “these models could predict the occurrence of an effect of lutein on the protection of cells or molecules (e.g. DNA, proteins and lipids) in the human eye from oxidative damage in vivo.”
The NDA therefore concluded that it had taken into account, “one human intervention study in healthy subjects did not show an effect of lutein on visual acuity or glare sensitivity, that the results of this study were inconsistent as regards contrast sensitivity, and that the evidence provided for a mechanism by which lutein could exert the claimed effect in vivo in humans is weak.”
“…the evidence provided is insufficient to establish a cause and effect relationship between the consumption of lutein and maintenance of normal vision.”
