VisioNIR application references

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VisioNIR

Application Reference List

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Content Introduction 1. VisioNIR LS Applications .............................................................................................................. 4

1.1 VisioNIR LS for insulin content inspection of insulin suspensions on filling machines ........... 4 1.2 VisioNIR LS for Content Uniformity inspection on tablet presses .......................................... 5 1.3 VisioNIR for the inspection of freeze dried products in a product inspection machine ........... 6 1.4 VisioNIR LS for identity of unlabelled bulk in secondary packaging ....................................... 7 1.5 VisioNIR LS for identity on a capping machine ...................................................................... 8 1.6 VisioNIR LS for Blend Uniformity on a continuous mixer ....................................................... 9 1.7 VisioNIR LS for Blend Uniformity and Water content on a fluid bed granulator ................... 10 1.8 VisioNIR LS for membrane coating identification on a tablet printer .................................... 11 1.9 VisioNIR LS for bulk tablet inspection .................................................................................. 12

2. VisioNIR AS Application ............................................................................................................. 13

2.1 VisioNIR AS ......................................................................................................................... 13

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Introduction

Visiotec is a wholly owned subsidiary company of Uhlmann Pac-Systeme, who is the market leader world-wide in the field of packaging machines for the pharmaceutical industry. visiotec primarily focuses on high-end technology such as inline NIR. In pharmaceutical production, the conflicting targets of achieving a zero-defect factor on the one hand and high-speed production on the other hand have to be reconciled as quality assurance is top priority in the pharmaceutical industry. The solution is quite simple: The quality of the products must be assured while at the same time fully utilizing available capacities in terms of production and packaging machines thus ensuring a cost-efficient production. The quality target must be pursued uncompromisingly because an incorrect product or dosage might have disastrous consequences for the patient’s health. A certification according to internationally recognized quality standards as, for example, the GMP guidelines, is a matter of course for the producers of pharmaceutical products and they have developed their quality management system into an integrated pharmaceutical process. However, a certification of this kind does not reliably indicate how safe the pharmaceutical production process really is because a system with a 100% quality control has not been available up to now. This is not surprising in view of the high output figures attained by the machines which make it difficult to inspect each single process to 100%. Up to now, other system producers have failed to successfully eliminate this quality gap. The technological advancements achieved meanwhile, however, have made it possible to attain a degree of safety which surpasses the level achieved by applying mathematical and statistical methods. To the point: 100% safety and therefore 100% quality thus satisfying the key demand in pharmaceutical production. A product quality control based on the NIR technique has already been successfully employed in the laboratories of the pharmaceutical companies. However, this is not an online quality control which is performed by statistical models when samples are taken into the laboratory for testing. Thanks to the development of computer systems of increasing efficiency, it is now possible to carry out a real-time product control. The basic idea is to perform a high-speed production and packaging control which does not impair the production process. The second innovative feature is the fact that the traditional random sampling techniques have become obsolete. It is true that they are almost 100% correct; however, the quality inspection process does not cover each single product or process. What is needed is a final product quality control during the packaging process which ensures a 100% exclusion of all possible defects. NIR stands for product control based on a spectral analysis, meaning - and this is the real innovation - an identification and determination of a product’s ingredients, its content and mixture in the near infrared range with a wavelength between 800 und 2100 nm. This range is particularly interesting for spectral comparisons and, in analogy to criminal investigation; it can be referred to as a molecular fingerprint. Apart from the inspection of solids, VisioNIR can be employed also for liquids and powders.

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1. VisioNIR LS Applications

1.1 VisioNIR LS for insulin content inspection of insulin suspensions on filling machines The non-destructive 100% inspection of the insulin content in cartridges directly after the filling process is an important tool to find process issues: At the end of the batch the insulin content was dramatically decreased. The used HPLC destructive method allows only sampling whereby the VisioNIR measures the insulin content of each cartridge. Thus, the endpoint of OOS products can be inspected and no in specification products must be rejected. During the filling process some of the filling nozzles were blocked and the cartridges were only partially filled. By the use of the 100% NIR these outliers were detected and rejected from the production stream. The production speed of the machine was 14.400 cartridges per hour and the accuracy was 1% SD.

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1.2 VisioNIR LS for Content Uniformity inspection on tablet presses The content uniformity and the compaction force are the most important tablet properties in the tableting process and the subsequent drug release. Upstream process steps can lead to segregation of API and excipients and inaccurate adjustments at the tablet press results in OOS compression forces. The inline NIR system is integrated in the tablet press directly after the compaction process to measure each individual tablet in terms of Content Uniformity and hardness. Non conforming tablets can be rejected. The production speed was 126.000 tablets per hour and the received accuracy was <1% RMSEP.

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1.3 VisioNIR for the inspection of freeze dried products in a product inspection machine The drug shelf life depends on the residual moisture content of the lyophilization cake and the presence of defined defects such as melt backs, shrunken cakes and collapsed cakes. Furthermore the identity of the right product must be confirmed since more than five different products are inspected on the machine. The inline VisioNIR determines those defects inside a product inspection machine after the lyophilization process as a final quality concept to avoid that any non-conforming products will reach the marketplace. With one scan the residual water content, different cake defects and the identity is determined in one step. The production speed was 400 vials per minute and the accuracy for the residual water determination was 0.04% RMSEP.

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1.4 VisioNIR LS for identity of unlabeled bulk in secondary packaging The customization after the primary packaging is often done at different production plants or after storage periods of the unlabeled bulk. The used colored ring marking method provides no information of the real content of the container and does not eliminate the risk of dangerous mix-ups entirely. The VisioNIR scans each individual container on the labeler before labeling and ensures that the correct drug with the right dosage is present. Non conforming products will be rejected. The process speed is up to 600 per minute.

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1.5 VisioNIR LS for identity on a capping machine Two different freeze dried products are running on a capping machine. The VisioNIR LS was installed in order to check each individual vial for identity. The process speed is 400 vials per minute.

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1.6 VisioNIR LS for Blend Uniformity on a continuous mixer The Blend Uniformity plays an important role in the continuous blending process. The homogeneity of API and excipients must be ensured to pass on to the downstream tableting process. The VisioNIR LS was installed on the exit chute of the continuous blender and the powder stream was measured with 50 spectra per second to ensure inspecting as much product as possible. The received accuracy was <1% RMSEP

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1.7 VisioNIR LS for Blend Uniformity and Water content on a fluid bed granulator 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. The VisioNIR LS was installed on a fluid bed granulator to determine the Blend Uniformity and the water content inline during the spraying and drying phase of the granulation.

The accuracy was <1.5% RMSEP for the Blend Uniformity and <0.4% RMSEP for the water content.

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1.8 VisioNIR LS for membrane coating identification on a tablet printer The presence of the membrane coating is important for the drug time resolved drug release in OROS tablets. The VisioNIR LS was installed on a tablet printer for the inline identification of the membrane coating and for the identification of the right active ingredient content core.

The process speed was 150.000 tablets per hour.

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1.9 VisioNIR LS for bulk tablet inspection After production bulk tablets are often inspected by camera systems to detect cosmetic defects. The additional use of the inline NIR technology assures the Content Uniformity. The so called “batch safer” machines are often used if batch release failed and 100% product inspection is required. The VisioNIR LS was installed on a tablet handling machine to determine the Content Uniformity of each individual tablet. The process speed is up 180.000 tablets per hour.

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2. VisioNIR AS Application

2.1 VisioNIR AS During patient individual packaging of tablets into personalized blister the presence and the right order of the individual tablets is of particular importance. The VisioNIR AS system was integrated on blister machines in order to inspect if each single blister contains the right tablets whereby more than 400 different products were packed on the blister lines.

The machine speed was 50 -80 and 200 tablets per second.