Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Elemental Impurities in Drug Products: Challenges for the pharmaceutical industry in establishing limits based on ICH Q3D for alternative routes of administration ***

Stefanie Rodler (Abschlußjahr: 2019)

Summary
Language: English
ICH guideline Q3D aims to control elemental impurity levels in drug products and is intended for all drug delivery forms but at present only contains scientifically evaluated elemental impurity limits for products administered either orally, parenterally or via inhalation.
The obligation to apply ICH Q3D also to drug products which are intended for other routes, like transdermal or transmucosal administration, challenges the pharmaceutical industry as currently only a rough guidance is provided on how to derive route-specific exposure limits.
Products administered via the cutaneous and transdermal route remain the largest area where PDEs for elemental impurities have not yet been fixed. Only limited information is available if or how the respective elemental impurities are absorbed via alternative routes like the skin. Further challenges in gathering information on route-specific absorption and bioavailability of specific elemental impurities are the comparability of published data or the use of non-standardised and outdated analytical methods resulting in an heterogeneous landscape of available information as basis for the ICH Q3D risk assessment.
In order to harmonise the requirements especially for the large field of products administered via the cutaneous and transdermal route, either guidance should be provided for the pharmaceutical industry on a scientific basis instead of direct application of oral or parenteral limits for all 24 listed elements by default or the strict obligation for an elemental impurity assessment according to ICH Q3D should be reconsidered for cutaneous and transdermal drug products keeping in mind the formidable barrier properties of the skin’s stratum corneum against external influences and xenobiotics.
The given PDE limits in ICH Q3D for oral, parenteral or inhalation products facilitate the performance of risk assessments for the pharmaceutical industry leading to a harmonised approach and an outcome which can also be easily assessed by regulators. Due to the lack of available data or generally agreed limits in terms of elemental impurities for products administered by alternative routes, the efforts in evaluating the risk of potentially contained unwanted elements for both the pharmaceutical industry and regulators are much higher, even leading to divergent outcomes and a lack of global harmonisation, respectively.
Pages: 50