title: A quality control method enhancement concept-Continual improvement of regulatory approved QC methods.
abstract: Quality Control methods (QC-methods) play an important role in the overall control strategy for drug manufacturing. However, efficient life-cycle management and continual improvement are hindered due to a variety of post-approval variation legislations across territories and a lack of harmonization of the requirements. As a result, many QC-methods fall behind the technical development. Developing the QC-method in accordance with the Quality by Design guidelines gives the possibility to do continual improvements inside the original Method Operable Design Region (MODR). However, often it is necessary to do changes outside the MODR, e.g. to incorporate new technology that was not available at the time the original method was development. Here, we present a method enhancement concept which allows minor adjustments, within the same measuring principle, outside the original MODR without interaction with regulatory agencies. The feasibility of the concept is illustrated by a case study of a QC-method based on HPLC, assumed to be developed before the introduction of UHPLC, where the switch from HPLC to UHPLC is necessary as a continual improvement strategy. The concept relies on the assumption that the System Suitability Test (SST) and failure modes are relevant for other conditions outside the MODR as well when the same measuring principle is used. It follows that it should be possible to move outside the MODR as long as the SST has passed. All minor modifications of the original, approved QC-method must be re-validated according to a template given in the original submission and a statistical equivalence should be shown between the original and modified QC-methods. To summarize, revalidation is handled within the pharmaceutical quality control system according to internal change control procedures, but without interaction with regulating agencies.
authors.affiliation: Department of Engineering and Chemical Sciences, Karlstad University, SE-651 88 Karlstad, Sweden.
authors.forename: Dennis
authors.initials: D
authors.lastname: Åsberg
authors.affiliation: Cambrex R & D, SE-691 33 Karlskoga, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: Cambrex R & D, SE-691 33 Karlskoga, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Olsson
authors.affiliation: Department of Engineering and Chemical Sciences, Karlstad University, SE-651 88 Karlstad, Sweden.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Samuelsson
authors.affiliation: AstraZeneca R & D, SE-431 83 Mölndal, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Svensson
authors.affiliation: AstraZeneca R & D, SE-431 83 Mölndal, Sweden.
authors.forename: Silke
authors.initials: S
authors.lastname: Klick
authors.affiliation: AstraZeneca, Charter Way, SK10 2NA Macclesfield, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Ennis
authors.affiliation: AstraZeneca, Charter Way, SK10 2NA Macclesfield, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Butterworth
authors.affiliation: AstraZeneca, Charter Way, SK10 2NA Macclesfield, UK.
authors.forename: Denise
authors.initials: D
authors.lastname: Watt
authors.affiliation: AstraZeneca, Charter Way, SK10 2NA Macclesfield, UK.
authors.forename: Stavroula
authors.initials: S
authors.lastname: Iliadou
authors.affiliation: AstraZeneca R & D, SE-431 83 Mölndal, Sweden.
authors.forename: Angelica
authors.initials: A
authors.lastname: Karlsson
authors.affiliation: Medimmune, Medimmune Way, MD 20878 Gaithersburg, USA.
authors.forename: Joanne T
authors.initials: JT
authors.lastname: Walker
authors.affiliation: AstraZeneca, Charter Way, SK10 2NA Macclesfield, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Arnot
authors.affiliation: AstraZeneca R & D, SE-431 83 Mölndal, Sweden.
authors.forename: Norb
authors.initials: N
authors.lastname: Ealer
authors.affiliation: AstraZeneca R & D, SE-431 83 Mölndal, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hernqvist
authors.affiliation: AstraZeneca, SE-152 57 Gärtuna, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Svensson
authors.affiliation: AstraZeneca, Charter Way, SK10 2NA Macclesfield, UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Grinell
authors.affiliation: AstraZeneca, SE-152 57 Gärtuna, Sweden.
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Quist
authors.affiliation: AstraZeneca R & D, SE-431 83 Mölndal, Sweden. Electronic address: Anders.AS.Karlsson@astrazeneca.com.
authors.forename: Anders
authors.initials: A
authors.lastname: Karlsson
authors.affiliation: Department of Engineering and Chemical Sciences, Karlstad University, SE-651 88 Karlstad, Sweden.
authors.forename: Torgny
authors.initials: T
authors.lastname: Fornstedt
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004345:Drug Industry / Q000592:standards*; D004364:Pharmaceutical Preparations / Q000592:standards*; D011786:Quality Control; D058996:Quality Improvement
chemical_list: D004364:Pharmaceutical Preparations
keywords: Continual improvement; HPLC; Method enhancement concept; Method transfer; Quality by design