COVER STORY:FUTURE PROOFKRAEMER & ISCHI ON

TABLET QUALITY CONTROL

AUGUST 2015

By Kraemer & Ischi

In truth, it comes down to a combination of all of these aspects. Today there are more challenges than ever before as the pharmaceutical industry endeavours to make products safer by guaranteeing that they

are of the highest quality, protect operators by ensuring safety in the production environment and save time and money through the use of fl exible systems that speed up release times.

The current industry buzzwords are ‘continuous production’. Sure, it sounds promising and somehow infi nite, but what does the industry need to make it happen? Kraemer Elektronik and Charles Ischi are complementing the whole pharmaceutical development and manufacturing process with a small but very important contribution — quality control of tablets and capsules.

Operator and environment protection

In a comparatively short time, containment systems that protect operators from extremely active or toxic ingredients have taken a signifi cant step forward and containment strategies and technologies in the pharmaceutical industry have altered a great deal during the past decade.

The pharmaceutical industry is still the driver of new and improved containment solutions that provide better protection of operators and better cleaning to avoid cross contamination of different products and because of these requirements, we had various requests from customers to fi nd a more cost-effi cient solution.

Containment manufacturing operating costs can approach hundreds of thousands to millions of euros and a major contributing factor is the time taken to change between products and cleaning. The most up-to-date containment strategies merge the production process equipment with containment to keep the contaminated space as small as possible.

The UTS IP65i system is an addition to washable tablet presses for wash-in-place (WIP) or wash-off-line (WOL) applications for processing medium and highly potent products up to OEB (occupational exposure band) level 5. As an addition to the existing dust-proof and easy-to-clean testing systems UTS4.1-S10 and UTS IP LR, the UTS IP65i is claimed to be the fi rst fully washable, universal testing system. The UTS IP65i tests the physical parameters of tablets; their weight, thickness, hardness and diameter.

Modularity and fl exibility

There is an approach to design that divides a particular system into smaller parts, so-called modules that can be used in various systems but also made independently. This specifi c approach is called modular design or modularity in design. A standard modular system can be identifi ed by the following characteristics: functional sub-division into separate, scalable and reusable parts; well-defi ned modular interfaces; and usage of industry standards for interfaces.

Modular design offers exclusion and augmentation (meaning that a new solution is added by simply plugging in a new module), along with fl exibility in design and tangible cost reduction owing to shorter learning times and less customisation. Numerous examples of modular systems surround us in our everyday life. This modularity is an attempt to combine the benefi ts of customisation with those of standardisation.

The laboratory testing devices in the P-Series are designed to offer the latest technology, space-saving design and maximum fl exibility. The basic devices, models P2-P5, can be tailored to the operators needs at any time thanks to the 'Plug and Play' extension module. This also allows for the upgrading of the semi-automatic basic devices to a fully-automatic testing system at any time. The P5 version tests all fi ve parameters: hardness, weight, thickness, length and width.

PAT testing and uniformity checking

Nowadays, batches easily reach sizes of >1,000,000 tablets. However, only 30 tablets are used for content uniformity (CU) release testing. This same assay of samples is typically checked for other parameters such as weight, hardness, thickness and diameter. These huge batch sizes and the trend for the change to continuous production require rapid and accurate analysis methods such as the well-known parameter tester Universal Test System (UTS) from Kraemer Elektronik and the rapid NIR measurement device VisioNIR LS for CU from visiotec.

The UTS-Extended with integrated VisioNIR LS technology can check for these physical-chemical characteristics.

In some cases, the thickness or the bizarre shape of the tablets does not allow the transmission measurement. The solution is the possibility to switch via a multiplexer from transmission to refl ection mode to enable the user to measure each available tablet on the market. For detailed homogeneity inspection requirements, the tablet can be area-scanned in refl ection mode. The resulting plot is an image of the tablet showing the active pharmaceutical ingredient (API) content distribution in the tablet. On the other hand, the mean content of this multi-spot measurement can be used for an overall statement of the API content of the tablet. From a quality point of view, the RAS measurement provides more solid results.

As opposed to the required 30 samples, the UTS-Extended can increase the sampling size up to 240 samples per hour. The system can be run at-line confi guration for automated tablet feeding from a connected tablet press or as a standalone system in production or the laboratory. The reliable trend monitoring visualises the CU prediction value of each sampled tablet. Outliers can be safely identifi ed. The UTS-Extended is dedicated to real time release (RTR).

10-year forecast

According to Richard Denk, chair of the ISPE Containment Group, containment in 2025 will see a lot of changes in the design and implementation as well as better integration of current process technologies. The three focal areas for containment over the next 10 years will be process integrated containment, disposables and cleaning.

Process integrated containment calls for a better understanding between the process expert and containment expert. Containment implemented in the process instead of adapted to the process will be one of the biggest changes the pharmaceutical industry has had to accommodate. The aforementioned UTS IP65i is a good example of a step in this direction. A number of other containment integration solutions can already be found in the packaging industry.

Cleaning is an equally important consideration. It is currently a huge challenge in multi-purpose facilities and the situation is unfortunately predicted to worsen with the EMA (European Medicines Agency) having published new regulations.

Containment is a very complex interaction between process, room, containment technologies, validation, cleaning, waste and operators, so much so that it called for the ISPE Containment Expert Group’s formation in 2010. The group has just announced the impending launch of its Containment Manual, scheduled for November this year, offering comprehensive guidance on the containment lifecycle, from start to fi nish.

Flexible gains: Semi-automatic basic devices in the P-Series can be upgraded to a fully-automatic testing system

Keeping up: The UTS-Extended can check the CU of 240 sample tablets per hour, a much needed capability as batch sizes typically reach >1,000,000Future proofi ng

What requirements need to be met by a tablet testing system to guarantee a successful product release? Is it dependable upon the testing system’s quality, speed, technology, fl exibility or safety? Kraemer and Ischi explain…

Process integration: The UTS IP65i is a hermetically sealed and fully washable

automatic testing system

1 low hazard

2 moderately hazardous

3 hazardous

4 highly hazardous

5 very highly hazardous

6 extremely hazardous

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COVER STORY