| 191. |
|
|
| 192. |
- Åsberg, Dennis, 1988-, et al.
(författare)
-
A quality control method enhancement concept : Continual improvement of regulatory approved QC methods
- 2016
-
Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier. - 0731-7085 .- 1873-264X. ; 129, s. 273-281
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 193. |
- Öhlund, Gunnar, et al.
(författare)
-
Apex predator induces predator-rich ecosystem state innorthern lakes
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Large predators are disappearing from ecosystems around the world. If predator speciesfacilitate each other’s existence through niche construction, this development could causecascading predator collapses and reduce ecosystem resilience. However, the importance offacilitation for the assembly and function of predator communities remains poorly understood.Here, we show that a large piscivorous fish, the northern pike (Esox lucius), enables theformation of a numerous and diverse predator community by inducing a dwarf ecotype ofEuropean whitefish (Coregonus lavaretus). Pike increases the standing biomass of prey-sized(<200mm) whitefish with a factor of 12.6, allowing small-gaped fish species (Percafluviatilis, Lota lota, Salvelinus alpinus and Salmo trutta) to go from small-growinggeneralists, to large-growing piscivores. Similarly, a guild of piscivorous birds (Gavia arctica,G. stellata, Sterna paradisaea, S. hirundo, Mergus serrator and M. merganser) shift from amixed diet to relying mainly on whitefish prey in presence of pike. Through this regime shift,the functional piscivore biomass in the non-pike fish community increases with a factor of14.2, and the density- and species richness of piscivorous birds increase with factors of 2.08and 2.16, respectively. Our results demonstrate how feedbacks between presence/absence ofimportant predators and the phenotype of prey may keep complex ecosystems in predator-richor predator-depleted states.
|
|
| 194. |
- Öhlund, Gunnar, 1977-, et al.
(författare)
-
Ecological speciation in European whitefish is driven by a large‐gaped predator
- 2020
-
Ingår i: Evolution Letters. - : John Wiley & Sons. - 2056-3744. ; 4:3, s. 243-256
-
Tidskriftsartikel (refereegranskat)abstract
- Lake‐dwelling fish that form species pairs/flocks characterized by body size divergence are important model systems for speciation research. Although several sources of divergent selection have been identified in these systems, their importance for driving the speciation process remains elusive. A major problem is that in retrospect, we cannot distinguish selection pressures that initiated divergence from those acting later in the process. To address this issue, we studied the initial stages of speciation in European whitefish (Coregonus lavaretus) using data from 358 populations of varying age (26–10,000 years). We find that whitefish speciation is driven by a large‐growing predator, the northern pike (Esox lucius). Pike initiates divergence by causing a largely plastic differentiation into benthic giants and pelagic dwarfs: ecotypes that will subsequently develop partial reproductive isolation and heritable differences in gill raker number. Using an eco‐evolutionary model, we demonstrate how pike's habitat specificity and large gape size are critical for imposing a between‐habitat trade‐off, causing prey to mature in a safer place or at a safer size. Thereby, we propose a novel mechanism for how predators may cause dwarf/giant speciation in lake‐dwelling fish species.
|
|
| 195. |
|
|
| 196. |
|
|
