16-18 November 2021
A Danish pharmaceutical manufacturer of antiallergic products has received a so-called "Untitled Letter" from the FDA after an inspection at his production site in March 2016. The letter was issued because of deviations from diverse GMP rules. Unlike a Warning Letter, an Untitled Letter is issued by the FDA when there is no immediate danger for patients' health if the deviations observed are not corrected immediately. The FDA therefore uses such letters for less serious GMP deviations. By contrast with a Warning Letter, an Untitled Letter contains no statement warning the manufacturer that failure to promptly correct a violation may result in an enforcement action.
A Form 483 preceded the present Untitled Letter. This form contained all the inspection observations which - for the FDA - haven't been sufficiently reacted to. But also repeated deviations which had already been identified during an inspection in 2014 in the USA have been admonished.
In detail, the violations are:
Deviations in aseptic manufacturing due to inappropriate measures to prevent microbiological contamination
Insufficient calibration and inspection/maintenance of automatic, mechanical or electronic equipment
Failure in the stability programme
Furthermore, the FDA states that the response of the manufacturer to the Form 483 was insufficient. The FDA criticises that the responses to too many deviations was only that the procedures will be updated and training will be improved. For the FDA, there is a need for further discussion.
Please also see the detailed FDA Untitled Letter to the Danish manufacturer of antiallergic products.