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Examples for NIR applications

Application: Verification (‘ID-ing’) of un-labeled bulk right before customization in packaging

Application on a Bausch & Stroebel labeler

Manufacturers of liquid medication often produce multiple lots which will be customized at a later stage. I.e. the filled ampoules, vials etc. are stored as un-labeled bulk material until an order triggers a packaging lot. At this stage each product is labeled, i.e. customized. In order to avoid dangerous mix-up situations an inline installed NIR system identifies each product before it is labeled. The application is performed in real-time and to 100% vs. sample testing (InProcessControl/IPC), i.e. potential quarantine and lab testing times are obsolete.

Application: Measurement of overall tablet content uniformity

Application on a Fette tablet compacting machine

The compacting process of tablets performed on a tablet press is essential for the efficacy of a drug. The right compression force, the degree of humidity in the compound, particle size and other characteristics are critical parameters which are influenced or detectable in this processing step. An inline integrated NIR system checks for these physical-chemical characteristics (quality indicator) to rule out deficiencies. The application is performed in a non-destructive way in real-time and to 100% vs. destructive sample testing (e.g. HPLC). Also, the overall release time is significantly reduced.

Application: Measurement of insulin content in a suspension

Application on an Eisai particle inspection machine

Insulin (suspension) is typically tested using HPLC. With the introduction of NIR technology right at after the suspension is filled, each cartridge is checked for its insulin concentration. This allows running production down to the low-concentration threshold and therefore saves product as well as pinpointing irregularities in the filling nozzles and hoses and rejecting these outliers. The application is performed in a non-destructive way in real-time and to 100% vs. destructive sample testing (HPLC). Also, the overall release time is significantly reduced.

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Examples for NIR applications

Application: Verification of membrane presence within a time-release tablet

Application on an Ackley tablet printer

Manufacturers of time-release drugs depend on the presence of a membrane within the pharmaceutical product enclosing the API of the product. Only through a micro-drilled hole in the membrane can stomach liquids release the drug’s API and therefore release it over time for a long-lasting efficacy. The presence and integrity of this membrane can be checked using NIR technology. The application is performed in a non-destructive way in real-time and to 100% vs. destructive sample testing. Also, the overall release time is significantly reduced.

Application: Discrimination of tablets in a clinical study packaging actives & placebos

Application on an Uhlmann blister packaging line

The proper placement of active and placebo products during a clinical study is an essential part in new drug studies. The developers of a drug have to examine in detail the effects on test persons of active versus placebo medication, which requires the products to look alike and cannot be distinguished by the human eye or with traditional vision systems. VisioNIR can safely rule out mix-ups in packaging. In addition, lots already packaged which are ‘suspicious’ can be reliably re-inspected in the same way using VisioNIR technology.

Application: Measurement of residual moisture in freeze-dried (lyophilized) products in vials

Application on a WILCO inspection machine

Manufacturers of lyophilized products often face challenges of residual moisture in the product (typically in the lyo cake) which has a significant impact on the drugs shelf life. Other challenges in the lyophilization process are so called broken cakes and melt-backs. An inline NIR system can determine if any of the mentioned deficiencies are present. The application is performed in a non-destructive way in real-time and to 100% vs. destructive sample testing (Karl-Fischer). Also, the overall release time is significantly reduced.

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Examples for NIR applications

Application: Measurement of overall tablet product quality (Quality indicator) during bulk inspection and sorting process

Application on a Proditec 360° inspection machine

Bulk material is often inspected by optical means for cosmetic defects right after they are produced. The additional use of NIR technology in this step also assures the manufacturer of the correct chemical composition of the product. In combination one can be sure that a pharmaceutical product not only looks good but also is good ‘inside’ from the content point of view. The application is typically performed in real-time and to 100% before the bulk material is put into storage drums for further packaging processes.

Application: Measurement of moisture content and API in granulation & drying processes

Application in a Glatt fluid bed granulator

Demands for real-time analyzing of pharmaceutical manufacturing processes to ensure product quality and process stability are increasing. For example in fluid bed processing, information regarding moisture content in the material could only be determined indirectly by means of other physical parameters such as the exhaust air humidity. Important product characteristics such as moisture content and the homogeneity of the Active Pharmaceutical Ingredient (API) can be measured in real-time and directly using NIR technology.

Application: Measurement of blend uniformity in a continuous mixing process

Application on a Loedige continuous mixer

Today, mixing processes are already performed in a continuous way. In case of mixing pharmaceuticals, the uniformity of the blend is essential and information regarding Active Pharmaceutical Ingredient (API) dosing content a critical process parameter. Using high-speed NIR technology allows measuring the blend uniformity as well as controlling its dosing unit to maintain the desired mix of API. The application is performed in a non-destructive way in real-time and to 100% vs. destructive sample testing (e.g. HPLC). Also, the overall release time is significantly reduced.

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Examples for AMV applications

Application: Verification of micro-dosed powder filled into blister cavities

Application on a Harro Hoefliger drum filler

Medication nowadays is often administered via inhalable delivery technologies. Usually this requires packaging in very small masses with the requirement of sophisticated filling technology. In order to verify the packaged micro-dosed masses at production speeds an innovative and real-time capable system is necessary. The small masses dosed into blister cavities can be checked using AMV technology. The application is performed in a non-destructive way in real-time and to 100% vs. destructive sample testing (gross-tare checkweighing). Also, the overall release time is significantly reduced.

Application: Verification of micro-dosed powder filled into carpules

Application on a Bausch & Stroebel auger filler

Dosing small masses into a container used to require weighing cells in order to control the fill weight. This process requires the weigh cells to balance out and significantly reduces and impacts fill speed. Using VisioAMV now the measurement of the product stream can take place in 'free-fall' and therefore the filling process can be controlled at significantly higher filling speeds. Product can be powder, pellets or liquid. The application is performed in real-time and controls the filling process accordingly.

Application: Measurement of fill volume/mass in powder- or liquid filled vials

Application on a vial transporting system

Fill volumes are critical in the packaging of (sterile) filling processes into glass vials or other container types. Material variations in the container e.g. glass thickness on the bottom of vials are practically ruling out the use of conventional vision technology. Using AMV technology those variations are eliminated and the proper mass can be measured. The application is performed in a non-destructive way in real-time and to 100% vs. destructive sample testing (gross-tare checkweighing). Also, the overall release time is significantly reduced.

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visiotec GmbH Uhlmannstr. 14 – 18 88471 Laupheim Germany Phone +49 7392 702 8712 Email: sales@visiotec.info http://www.visiotec.info

USA +1 973 362 8885 info@visiotecamerica.com www.visiotecamerica.com

PAT Solutions, v4.1.2 / Information as per 12/2017 All rights reserved to visiotec GmbH; duplication and further use is permitted only upon prior approval by visiotec. The content of this brochure has been created with a great deal of care. However, no liability or warranty is assumed for the information contained herein, including technical specifications and statements being accurate, complete or current. visiotec reserves the right to revise or update any information or data without prior notice.

Examples for potential areas of implementation of AMV technology

Application: Measurement of product mass during filling process using a dosator system

VisioAMV functional principle for a dosator system

When a dosator system is used, there are two measurements performed using AMV technology. The filling, dosing and measurement steps are in this application as follows:

Dosing needle made of Peek material is dipped into powder bed loading powder content inside the needle body.

Dosing needle is then moved into VisioAMV sensor unit electrical field (arrow marked A) which is located directly over the container to be filled (e.g. a blister cavity).

1st VisioAMV measurement of dosing needle with the filled powder content inside takes place (section of VisioAMV evaluation graph numbered #1).

Dispensing of powder into container (arrow marked B).

2nd VisioAMV measurement of empty dosing needle takes place (section of VisioAMV evaluation graph numbered with #2). The difference between the two performed VisioAMV measurements correlates to the net dispensed mass.

Application: Measurement of capsule content during packaging

VisioAMV functional principle for a feeding system of capsules

When capsules are packed into blisters, a vision system is typically used to confirm cosmetic quality parameters such as presence, color and dimensions (length, size, etc.) of the products being packaged. However, the capsule itself is only a carrier for the active pharmaceutical ingredients and excipients located inside the capsule shell. The inside content can either be powder product or pellets. Using AMV technology in a dedicated blister feeding system right before the capsules are placed into the blister cavities can measure and confirm the correct fill level of product inside the capsule is present. The VisioAMV evaluation graph on the right-hand side functional principle of this application shows the sensor signals for different capsule fill levels.