Comparison of permitted daily exposure (PDE) values for active pharmaceutical ingredients (APIs) - Evidence of a robust approach.

Autor: Sehner C; Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach, Germany. Electronic address: claudia.sehner@boehringer-ingelheim.com., Bernier T; Abbott Laboratories GmbH, 31535, Neustadt Am Rübenberge, Germany., Blum K; GlaxoSmithKline, Prinzregentenplatz 9, 81675, Munich, Germany., Clemann N; F. Hoffmann-La Roche Ltd, 4070, Basel, Switzerland., Glogovac M; Novartis International AG, Lichtstr. 35, Basel, Switzerland., Hawkins WA; SafeBridge Europe Ltd., 33 St Andrews Street South, Bury St Edmunds, IP33 3PH, Suffolk, United Kingdom., Kohan M; SafeBridge Europe Ltd., 33 St Andrews Street South, Bury St Edmunds, IP33 3PH, Suffolk, United Kingdom., Linker F; Grünenthal GmbH, Zieglerstraße 6, 52078, Aachen, Germany., Lovsin-Barle E; Takeda Pharmaceuticals International AG, Glattpark-Opfikon, Switzerland., Osadolor O; AstraZeneca, Francis Crick Avenue, Cambridge, United Kingdom., Pfister T; F. Hoffmann-La Roche Ltd, 4070, Basel, Switzerland., Schulze E; Merck Healthcare KGaA, Frankfurter Str. 250, 64293, Darmstadt, Germany., Schwind M; Sanofi-Aventis Deutschland GmbH, 65926, Frankfurt, Germany., Tuschl G; Merck Healthcare KGaA, Frankfurter Str. 250, 64293, Darmstadt, Germany., Wiesner L; Takeda Pharmaceuticals International AG, Glattpark-Opfikon, Switzerland.
Jazyk: angličtina
Zdroj: Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2024 Jun; Vol. 150, pp. 105649. Date of Electronic Publication: 2024 May 21.
DOI: 10.1016/j.yrtph.2024.105649
Abstrakt: Permitted Daily Exposure Limits (PDEs) are set for Active Pharmaceutical Ingredients (APIs) to control cross-contamination when manufacturing medicinal products in shared facilities. With the lack of official PDE lists for pharmaceuticals, PDEs have to be set by each company separately. Although general rules and guidelines for the setting of PDEs exist, inter-company variations in the setting of PDEs occur and are considered acceptable within a certain range. To evaluate the robustness of the PDE approach between different pharmaceutical companies, data on PDE setting of five marketed APIs (amlodipine, hydrochlorothiazide, metformin, morphine, and omeprazole) were collected and compared. Findings show that the variability between PDE values is within acceptable ranges (below 10-fold) for all compounds, with the highest difference for morphine due to different Point of Departures (PODs) and Adjustment Factors (AFs). Factors of PDE variability identified and further discussed are: (1) availability of data, (2) selection of POD, (3) assignment of AFs, (4) route-to-route extrapolation, and (5) expert judgement and differences in company policies. We conclude that the investigated PDE methods and calculations are robust and scientifically defensible. Additionally, we provide further recommendations to harmonize PDE calculation approaches across the pharmaceutical industry.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The author and co-authors are employed by pharmaceutical companies.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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