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A quality control method enhancement concept: Continual improvement of regulatory approved QC methods
Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).ORCID-id: 0000-0001-8561-6872
Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för ingenjörs- och kemivetenskaper (from 2013).ORCID-id: 0000-0003-1819-1709
Vise andre og tillknytning
2016 (engelsk)Inngår i: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 129, s. 273-281Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
Elsevier, 2016. Vol. 129, s. 273-281
Emneord [en]
Continual improvement, HPLC, Method enhancement concept, Method transfer, Quality by design
HSV kategori
Forskningsprogram
Kemi
Identifikatorer
URN: urn:nbn:se:kau:diva-47560DOI: 10.1016/j.jpba.2016.06.018ISI: 000393847600035OAI: oai:DiVA.org:kau-47560DiVA, id: diva2:1060878
Forskningsfinansiär
Knowledge Foundation, 20140179ÅForsk (Ångpanneföreningen's Foundation for Research and Development), 15/497Swedish Research Council, 2015-04627Tilgjengelig fra: 2016-12-30 Laget: 2016-12-30 Sist oppdatert: 2019-11-04bibliografisk kontrollert
Inngår i avhandling
1. Fundamental and Regulatory Aspects of UHPLC in Pharmaceutical Analysis
Åpne denne publikasjonen i ny fane eller vindu >>Fundamental and Regulatory Aspects of UHPLC in Pharmaceutical Analysis
2017 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Ultra-high performance liquid chromatography (UHPLC) provides a considerable increase in throughput compared to HPLC and a reduced solvent consumption. The implementation of UHPLC in pharmaceutical analysis, e.g. quality control, has accelerated in recent years and there is currently a mix of HPLC and UHPLC instrumentation within pharmaceutical companies. There are, however, technical and regulatory challenges converting a HPLC method to UHPLC making it difficult to take full advantage of UHPLC in regulatory-focused applications like quality control in pharmaceutical production.

Using chromatographic modelling and fundamental theory, this thesis investigated method conversion between HPLC and UHPLC. It reports on the influence of temperature gradients due to viscous heating, pressure effects and stationary phase properties on the separation performance. It also presents a regulatory concept for less regulatory interaction for minor changes to approved methods to support efficient life cycle management.

The higher pressure in UHPLC gave a retention increase of up to 40% as compared to conventional HPLC while viscous heating, instead, reduced retention and the net result was very solute dependent. Selectivity shifts were observed even between solutes with similar structure when switching between HPLC and UHPLC and an experimental method to predict such selectivity shifts was therefore developed. The peak shape was negatively affected by the increase in pressure for some solutes since secondary interactions between the solute and the stationary phase increased with pressure.

With the upcoming ICH Q12 guideline, it will be possible for the industry to convert existing methods to UHPLC in a more flexible way using the deeper understanding and the regulatory concept presented here as a case example.

Abstract [en]

Ultra-high performance liquid chromatography (UHPLC) provides a considerable increase in throughput compared to conventional HPLC and a reduced solvent consumption. The implementation of UHPLC in pharmaceutical analysis has accelerated in recent years and currently both instruments are used. There are, however, technical and regulatory challenges converting a HPLC method to UHPLC making it difficult to take full advantage of UHPLC in regulatory-focused applications like quality control in pharmaceutical production. In UHPLC, the column is packed with smaller particles than in HPLC resulting in higher pressure and viscous heating. Both the higher pressure and the higher temperature may cause changes in retention and selectivity making method conversion unpredictable.

Using chromatographic modelling and fundamental theory, this thesis investigates method conversion between HPLC and UHPLC. It reports on the influence of temperature gradients due to viscous heating, pressure effects and stationary phase properties on the separation performance. It also presents a regulatory concept for less regulatory interaction for minor changes to approved quality control methods and how predicable method conversion is achieved by improved understanding.

sted, utgiver, år, opplag, sider
Karlstad: Karlstads universitet, 2017. s. 75
Serie
Karlstad University Studies, ISSN 1403-8099 ; 2017:9
Emneord
Liquid chromatography, UHPLC, Pharmaceutical analysis, Adsorption isotherm, Design of experiments, Quality control
HSV kategori
Forskningsprogram
Kemi
Identifikatorer
urn:nbn:se:kau:diva-47852 (URN)978-91-7063-756-8 (ISBN)978-91-7063-757-5 (ISBN)
Disputas
2017-04-06, 9C204, Rejmersalen, Karlstads universitet, Universitetsgatan 2, Karlstad, 10:00 (engelsk)
Opponent
Veileder
Forskningsfinansiär
Swedish Research Council, 2015-04627ÅForsk (Ångpanneföreningen's Foundation for Research and Development), 15/497
Tilgjengelig fra: 2017-03-08 Laget: 2017-02-10 Sist oppdatert: 2019-06-10bibliografisk kontrollert

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Åsberg, DennisSamuelsson, JörgenFornstedt, Torgny

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