Many technology and industry sectors including energy, medicines, food, chemicals, etc. are being revolutionized by the design, synthesis, characterization, and application of devices and materials on a nanometer scale, better known as nanotechnology.
This is because the chemical, physical and biological properties of bulk matter are completely different from the properties at nanoscale.
The NanoFlowSizer from InProcess LSP
Nanoparticles and its Applications
Nanoparticles are synthetic and natural particles with a size in the 10-9 m range (1-1000 nm). They have a large surface area in relation to their volume due to their small size, conferring them special properties. Nanoparticles are present in a lot of items in our every-day life, like scratch-proof glasses, medicines, or transparent sunscreens.
Of particular interest for the pharmaceutical industry, nanoparticles are utilized under different formulations, like engineered drug delivery systems targeted to disease cells, reducing damage to healthy ones.
In addition to the major applicability in oncology, a number of vaccine formulations are based on nanoparticle vehicles that contain the active vaccine. Liposomes and other lipid-based nanoparticles (LNP) play an important role as vaccine carriers in the medical industry. Therefore, liposome synthesis is a highly increasing market.
The Importance of Particle Size Monitoring
The ability of nanoparticles to perform their function depends on their size. In addition, size distribution is directly related to safety and efficacy (for patients in pharma applications). Nanoparticle size control is paramount to the entire development and manufacturing process of nanoparticle products, as the behavior of particles at the nanoscale is highly dependent on these properties.
The pharma industry must have total control over the production processes of its high-quality products being compliant with stringent demands and regulations. This could cost several € millions/day. So, they need highly efficient and sophisticated Process Analytical Technologies (PAT) which enables continuous insight in process performance in real-time.
Yet, something that hinders nanoparticle applications from reaching full potential is a lack of adequate PAT solutions for monitoring particle size and size distribution in the nanoscale regime. It was recognized by health agencies that one of the greatest challenges in bringing new nanomedicines to the market is accurately determining their particle size during manufacturing.
Economic Losses Due to Lack of Solution
The offline analysis approach and associated costs of laboratory usage and personnel were estimated at € 600-700K per drug per year by one of the largest pharmaceutical companies. Additional costs related to lost production capacity, by pausing the production process for offline testing and feedback, were not estimated as a concrete number but are expected to be significantly higher.
Their low-efficiency and effectiveness in quality control brings about a high occurrence of production batches being not compliant or even rejected: creating losses as high as €2 million per event with up to 50% of all cases for complex, less-routine processes
No Real Solutions Available?
For non-solid products, direct inline (under flow) measurement of nanoparticle size and distribution is crucial to ensure the quality of routine production. Yet, there are no such inline systems currently on the market since the release in 2019 of InProcess-LSP's NanoFlowSizer technology.
Sampling procedures are required for the technologies which are now utilized (mostly Dynamic Light Scattering) and, in most cases, off-site laboratory analysis and sample treatment (quiescent conditions created, diluted, etc.), which presents severe problems:
- Need for laboratory analysis: incurring in laboratory costs (material, equipment, personnel)
- Low control over the production process: Due to long feedback time by offline analysis process control options are poor and far from real-time.
- Non-representative offline measurement conditions and possible interference with the sterility of the process (invasive process).
- Long time for analysis (10 min - hours): Limiting the number of samples and representativity and increasing the total production time.
- Impossibility to measure unstable formulations, since sampling will disrupt the physical and chemical composition immediately.
- Sub-optimal process performance: variations in product quality because of the absence of full process control
- Impossibility to carry out continuous manufacturing (24 hour) because of the dependence on laboratory analysis and the requirement to interrupt production flow.
In order to overcome the limitations of conventional DLS for Process Analytical Technologies, InProcess-LSP developed a new innovative technology: Spatially Resolved Dynamic Light Scattering (SRDLS). SR-DLS allows particle size characterization in process flow and is able to measure highly turbid suspensions without dilution. In 2019 InProcess-LSP has fully released the NanoFlowSizer as the only TRUE inline particle size measurement technology.
Why can NanoFlowSizer Perform Inline Analysis?
The key innovation in the NanoFlowSizer is that it employs Spatially Resolved Dynamic Light Scattering (SR-DLS) based on Fourier Domain Low-Coherence Interferometry (FD-LCI). FD-LCI Light scattering information is gathered from particles at different depths in the sample. The spatially or depth-resolved signal offers new and exciting possibilities of which measurement in flow is one of the most important advantages.
The unique depth-resolved light scattering information is key and holds information on both particle size and process flow characteristics. The patented algorithms of the XsperGo software can extract the relevant information continuously, supplying size characteristics every 10 seconds.
|| Needs covered
|Inline, online, at-line, and offline
|| Versatility, Various scales
||Complete control over the production process and product quality:
- Batch rejection related to particle size reduced - saving up to €2 million per event
- 24/7 production possible: increasing revenues
|| Suitable for sterile processes
No need for sampling or sample treatment (no expensive time-consuming laboratory testing): €670,000 per drug saved annually, plus increased productivity
|Particle size information within seconds
|10 – 1,000 nm range
|| Highly-concentrated products
NanoFlowSizer is made up of three main elements (Figure 2):
- XsperGo software: Instrument control and particle size characteristics calculations
- Probe Unit: Interferometer + Optics
- The Base Unit: With the spectrometer and light source
Figure 2. NanoFlowSizer system, Image Credit: InProcess-LSP
The NanoFlowSizer is a flexible modular system that, depending on the module used, provides different functionalities (Figure 3) for various scales.
- Offline: At a location not being the production facility, i.e., laboratory (sampling required)
- At-line: Static measurements carried out in proximity to the production process (sampling required)
- Online: Connected to the production flow by a sampling loop
- Inline: In the production flow (continuous real-time measurements, no need for sampling and sample treatment
Figure 3. NanoFlowSizer modules (above) and configuration (below). Image Credit: InProcess-LSP
Covering a large scope of customer applications, the modular design enables configuration for all four analysis classifications listed varying from ml scale up to multiple Liter scale. The non-invasive measurement process takes 10 seconds for nanoparticle size and particle size distribution.
Real-time process feedback information is enabled by the continuous analysis mode; this is crucial for high quality control of any production process. The NanoFlowSizer is also applicable to sterile production conditions because measurements are carried out non-invasively without any direct contact with the suspension itself.
In Summary, How the NanoFlowSizer Differs!
When considering offline functionality, compared to current particle sizers for highly turbid and concentrated samples, the NanoFloSizer provides better performance as it does not require sample preparation.
As a unique and only inline nanoparticle size analyzer, the NanoFlowSizer is the only system currently on the market that provides all of the advantages associated with this inline analysis functionality. It does not require sampling before analysis and decreases risks like contamination and errors related to testing and sampling.
Additionally, continuous monitoring of process performance is possible as inline measurements only takes seconds, giving a complete insight of the production process with real-time performance feedback.
Finally, NanoFlowSizer provides superior process control, optimizing the state of control and compliance, and decreasing risks for batch-rejections related to particle size.
This information has been sourced, reviewed and adapted from materials provided by InProcess-LSP.
For more information on this source, please visit InProcess-LSP.