Milk is the largest segment in food market and milk drink is still the highest consumed dairy product in the world, followed by butter and cheese. Dairy products are considered as a part of the healthy diet and different nations have recommendations for daily milk or dairy products intake. Thus, the dairy product consumption is rising globally. 

The growing consumption brings pressure to the industry for more enhanced processes. Dairy processors focus on quality, compliance with product safety regulations and hygiene in the process. Efficient raw material usage with proper waste management system ensures cost and resource efficiency. Sustainability is an increasingly important focus area and with suitable process monitors, optimization and measurement tools manufacturers can more easily meet their targets on sustainability, use material efficiently and reduce waste. Accurate process measurements can increase dairy processing profitability and yield with accurate process measurements. 

Various dairy processing procedures

Milk consists mainly of water, fat, proteins, lactose (milk sugar) and minerals (salts). The residue, when water and gas are removed, is called the dry matter (DM) or total solids (TS) content of the milk. Industries are using several processing procedures for dairy products, such as:

Evaporation and drying

Evaporating milk to higher solids content and dried to powder makes the product lighter in weight, easier and cheaper to transport as more product can fit into a smaller space. Powder’s shelf life is also longer, and the product is easier to handle and ship as pathogens usually require moist or wet conditions to develop. Thus, milk powders are the most traded agricultural commodities globally.

Milk is also evaporated to a certain extend when it is processed into condensed milk or sweetened condensed milk. All of these operations need tight evaporation control, and a common measurement scale is Brix or total solids (TS) measurement.

Total solids and product identification

Fresh milk, usually packed in milk cartons, has a lot of product options, varying between fat-free skim milk to whole milk. Due to its short shelf life this product is more of a local commodity. In the manufacturing, all fat is first removed from the raw milk and then added back according to legal standard and recipe. This processing step is called standardization, and this is a critical step as each nation has different regulations on the composition of milk.

Homogenization is a common step after standardization, and it reduces the fat molecules into such a small size that they do not rise up and create a creamy layer on top of the milk. When producing fresh milk, the producers want to measure the total solids content (TS) accurately and in-line to meet the legal standards and to create products while creating minimum waste. Fast milk product identification in-line enables better yield, leading to savings to producers by minimizing product waste and prohibiting product mixes and expensive product recalls.

Infant formula

Baby milk is a synthetic version of breast milk designed to be used as an additional alimentation or as a substitute to fulfill an infant’s nutritional needs. Producers want absolute certainty in hygienic conditions as well as in product safety while protecting the nutritional value of the product. In the manufacturing process, total solids (TS) measurement is a critical measurement for any infant formula manufacturer.

Product blending and flavoring

Milk, dairy, yogurt, ice cream and alternative milk products might be blended with jam, flavors and syrups to create delicious commodities. The correct and accurate blend is essential in this process.

Measuring the process with Vaisala’s refractometer

In addition to the tight process control and hygienic process conditions, accurate and reliable measurements from the process are required for better profitability as well as clean, safe and familiar tasting food, made precisely according to a recipe.

Vaisala’s solution for the dairy production process optimization is the Sanitary Process Refractometer PR-43 system, which consists of a compact or probe refractometer and a graphical user interface bringing ease of use into play. The refractometer can be also used as a stand-alone device. Different user interface options range from rugged to a compact lightweight and a web-based version, and allow the user to select the most preferred way to access and use the refractometer measurement and diagnostics data.

The measurement of the refractometer is not affected by bubbles, particles or vibration. The hygienic design has 3-A certificate and the product can handle cleaning-in-place (CIP) and sterilization-in-place (SIP) operations. The refractometer covers the full Brix range 0-100 %.

Learn more about the different processes and how a refractometer can help to control, optimize and save raw material and energy from our Dairy processing optimization eBook!

End of 2018, Vaisala acquired Finnish K-Patents Group, a pioneer in in-line liquid measurements for industrial applications. The acquisition enables Vaisala to expand its technological expertise and product portfolio from gas into liquid measurements. The new product area, Liquid Measurements, brings renowned Refractive Index (RI) technology and in-line process refractometer products available for many types of industrial process control applications.

Basics of refractometry

Scientists consider refractive index (RI) measurement an ideal way to measure liquid concentrations.
The procedure is relatively simple and based on refraction of light. One simple example of this property of light shows up when one puts a pencil in a glass of solution. It appears the pencil bends when in fact the light bends.

Many experience this phenomenon first-hand, for example with a straw in soda or juice, or with oars of a rowboat.

An important point of the measurement principle is to understand that even if there are particles or gas bubbles in the solution, the bending angle is the same as in clear solutions. Particles or bubbles have no influence on the bending angle, so the only thing influencing the bending angle is the change in the solution’s concentration.
 

The critical angle

The study of the property of light has developed into the science of refractometry.

Light travels at different speeds in different media. The denser a medium the slower the speed of light in that medium. When light passes from one medium to another at any angle other than 90°, it changes not only speed but also direction at the boundary between the two media. When a light beam enters the liquid, it is partly refracted to the liquid and partly reflected away. The point where the total reflection starts is called the critical angle.

In most solutions, the concentration of solute in a solvent can be determined by measuring the RI. The relation between the refractive index and the concentration depends on the solvent and solute, temperature, as well as wavelength.

In practice, the wavelength-dependency (dispersion) is avoided by using monochromatic light. The temperature dependency is compensated mathematically by using a compensation formula.

Combining truly digital process refractometer with robust design

The RI was first developed as a lab technique that later made a transition into process measurement once the refractometers developed and got much more sturdy. In-line refractometer construction in the process must withstand harsh, demanding conditions that can include caustic elements, vibration, dust, heat, pressure or a combination of these.

K-PATENTS® developed digital process refractometers determine the RI of the process solution by measuring the critical angle of refraction. The critical angle is measured by a digital CCD-camera. The process refractometer provides a 4 to 20 mA DC output or Ethernet signal proportional to temperature compensated process solution concentration.

The refractometer advances the K-PATENTS® patented CORE-optics (Compact Optical Rigid element), which incorporates all optical components LED (light emitting diode), lenses, prism and CCD-camera as well as the temperature element pT-1000 in one rigid module. The CORE optics module is isolated from the refractometer body, and therefore external forces such as pressure, flow, and temperature changes do not influence the measurement. There is no need for regular maintenance due to the construction with no moving parts, no trimpots and with the solid-state CORE-optics.

The same principle is applied to various refractometer model designs that are easy to install in small or large pipes, tanks and reactors. Applications range from potentially explosive hazardous substances to chemically aggressive liquids that require special alloys or non-metallic parts, such as fab chemicals used in semiconductor wafer processing.

Vaisala K-PATENTS® process refractometers are enclosed, operate continuously, interfacing with other elements of a process control system, and are more expensive than e.g. portable instruments, because of their ruggedness and complexity, necessary elements to perform reliable in-process monitoring.

With the unique and patented refractive index technology, build-in temperature measurement and digital measurement principle, the measurement drift is not possible, which makes the K-PATENTS® innovated refractometers unique and a winning measurement solution for all liquids.

In this blog, we answer questions we received during our recent webinar about The Benefits of Refractive Index (RI) in Development and Production of Active Pharmaceutical Ingredients (APIs). 

The webinar recording is available here.
A blog about the topic is available here.
Explore all refractometer applications for pharmaceutical drug manufacturing and biotechnology processing. 

You mentioned USP Class VI. It is important to indicate also the temperature at which this is valid, for example 121°C.

The modified PTFE used as the prism gasket material has been tested accordingly with the USP Class protocol for plastics at 70°C. In case a higher temperature is required, please specify this in the beginning of the project where the suitable product for the application is selected.

Do you have any slides that show how sensitive the refractive index is to temperature (lab data)?

Typically, one centigrade in Celsius corresponds to ± 0,1% in concentration, but it is good to take into consideration that it depends on the chemical or substance measured. Each refractive index value will be calibrated to match the chemical curve for that particular measurement and application.

Is the refractometer certified for use in hazardous areas?

We also supply Intrinsically Safe Process Refractometers that can be used in hazardous locations in Zone 0, Zone 1 and Zone 2. The refractometer is available with ATEX and IECEx certifications. 

In the cake wash example, the picture included a probe type being used in a very small tube apparatus. Was this because the end user wanted to scale up this probe refractometer for eventual production scale?

We have a compact, scalable pharma product model, which we presented, but in this particular case the customer chose to use a probe refractometer already at the lab, which is the same model they are using at different points in their pilot and full scale plants.

Can you comment on the accuracy of the RI measurements? If one were to quote the accuracy capability of the instrument?

The accuracy in terms of refractive index nD is ± 0,0002.

We perform a cooling crystallization step during API manufacturing. I am interested in detecting when the crystals start to form. Can I see the crystals with refractive index measurements?

The refractive index measurement is not influenced by suspended crystals in the slurry; therefore, we cannot “see” the crystals. However, you are probably interested in determining the point at which the crystals start to form, and that is possible by refractive index measurements. If you monitor the concentration of the mother liquor by a refractometer, you will be able to see how the concentration increases during cooling until a saturation or supersaturation point, after which the concentration starts to decrease. The concentration starts to decrease because the compound in the liquid or solvent starts to crystallize, and the mass transfer from the liquid to the solid means crystal formation. That is the point that you want to determine and monitor.

Can refractive index detect turbidity?

No, as turbidity is caused by suspended solids and refractive index is influenced only by the dissolved material of the solution.

How can I perform re-calibration of the refractometer?

The K-Patents refractometer presents no measurement drift. This means the refractometer is shipped to your factory calibrated for refractive index and will not require re-calibration. However, GMP guidelines require you do perform verification in a period defined by your company’s practice. K-Patents calibrates each refractometer using Cargille’s standard refractive index liquids over the full range. Therefore, the K‑Patents refractometer calibration can easily be verified on site using the N.I.S.T. traceable refractive index liquids. Instructions for the verification steps are given on the refractometer’s display. A report of the verification results can be printed and signed.

I have a distillation process for a chloroform-ethyl acetate mixture. Can I monitor in real-time the concentration of chloroform? We need this to stop the operation.

The boiling point for chloroform seems to be lower (61°C) than ethyl acetate (77°C), so chloroform should be your top product. You can certainly measure the concentration in real time with a refractometer, but in this case, it must be after the condenser. We would need to check refractive index range and temperature and other process details, but this should not be a problem, and this seems like a good application for the refractometer and a good opportunity to optimize your process. You can request to be contacted by us, and we can send you a form to fill with the required details for evaluation of your application.

Do you have any experience of the use of RI in high pressure systems, if so, what is the highest pressure tolerances the probes can take?

Based on our technical specification, we can supply the instrument to pressures up to 40 bar process pressure.

Explore all applications 

Joining forces – Vaisala and K-Patents

Want to learn more or to find out how K-PATENTS® Process Refractometers could help your process, please contact us.

Health is a crucially important social and economic asset, and the development of effective drugs goes hand in hand with the development of modern human and societies. We can cure, prevent and manage more diseases than ever. However, with emerging medical conditions and diseases, pharma researchers are constantly looking into new drug developments.

Drugs consists of two parts: the Active Pharmaceutical Ingredients (API), which are the disease healing components, and the appropriate chemically inactive excipients, which are the vehicle delivering the drug to the human or animal body. An important focus in pharmaceutical R&D and product engineering is exploring new API components to develop new, innovative and perhaps in the future, personalized medicines.

The Complexity of Pharmaceutical Manufacture

The development of new drugs is a high-risk, costly and long process. Just to give an idea, The Tufts Center for the Study of Drug Development estimated that bringing a drug to market costs over USD 2 billion, and according to Pharmaceutical Journal, only 1 of every 10 drugs that start the clinical phase make it to the market. Additionally, it takes around 10-15 years to develop a drug, and by the time it is available for sale there could be only 10 years to recoup the high investment cost. To balance the risks involved in making new drugs, many pharma companies manufacture generics, focusing on products from expired patents or slightly modifying a patent.

Other challenges for pharma companies are the tight regulations related to drug manufacturing and the elevated operating costs that follows. Drugs manufacturing requires a system which ensures that the final product meets predetermined specifications. The conventional approach has been to produce drugs in batch processes with separate steps, including lengthy storage times and off-line quality check after every stage. Batch production may even require that the intermediate product is transferred from one facility to another for further production steps. This approach ensures compliance and high-quality products, but it also creates major bottlenecks and inefficiencies in the process, extending the overall processing time and increasing production costs considerably.

This all affects the financial performance of the pharma companies and ultimately the costs of products to the patients and society. At the same time, there is an increasing pressure to bring drug prices down, and as a solution, pharma companies are looking into new ways of working. Many of the industry’s leaders are investing heavily in R&D in exploring technical solutions that can speed-up drug development time and make the process cost-efficient.   

Implementing Continuous Manufacturing (CM)

The Food and Drug Administration (FDA) is on the mission to support pharmaceutical innovation and modernization as part of their commitment of protecting and promoting public health. Based on this, the FDA has launched the Process Analytical Technology (PAT) initiative and published a framework, which supports the use of timely measurements and analytical tools that provide means for acquiring sufficient information for process understanding. The PAT strategy also provides the right foundation to move from batch processes to continuous manufacturing (CM) in pharmaceutical and biopharmaceutical production.

To implement CM, a full understanding of the process is required to create a control strategy that minimizes the incoming material variation. The drug’s critical quality attributes must be identified, as well as the production variables that have effect on them, in order to set acceptable deviation tolerances and define the correct PAT tools for monitoring and control. Real-time measurements from the early stages of drug discovery help to collect large amount of data to obtain scientific knowledge to mitigate risks associated with new drug development, and to design robust processes capable of delivering consistently high product quality.

Refractive Index as a PAT Tool

PAT involves not only using the conventional process sensors such as pressure, temperature and pH, but also new in-line analyzer technologies. One emerging technology is refractive index (RI), a direct measurement of liquid concentration based on the refraction of light. RI measurements have been adopted by other industries for decades - for example in pulp and paper for measurement of solid content of black liquor, and sugar industry for Brix measurement in sugar manufacturing   - but by the time the PAT initiative started it had still been fairly unexplored in the pharma sector.

A major advantage of RI is that it can be measured in-line by a process refractometer, supporting the current trend in pharma to move towards continuous processing. Process refractometers are mainly used for measuring, monitoring and controlling liquid concentrations. These measurements are also important in pharmaceutical processing as many processing steps are carried out in a liquid medium. But it is in the more unconventional applications where the principle behind the measurement, refractive index, offers many other opportunities for drug development and processing.

Refractive index measurements have proven to be accurate for product identification, even more than density and conductivity measurements, as every chemical has a distinctive refractive index value. This unique characteristic reveals the potential of refractive index as a PAT analytical tool in other applications such as interface detection between different solvents or between solvent and product, and reaction monitoring where the RI value of the mixture changes as reactants become products. In-line refractive index measurements provide a window to the process and information that could not be obtained by traditional laboratory off-line testing.

Refractive Index Brings Huge Potential for Fundamental Process Understanding

A study by a large pharmaceutical company in Europe few years back identified 11 potential applications for refractive index solely in API manufacture. The scientists concluded that when measuring RI in real-time, a process profile specific for the process is obtained, which can be used as a reference for LEAN development and scale-up of the process, and ultimately for reducing considerably the drug development work and time.

The benefits of the refractive index measurements are not limited to API manufacture. The RI measurements are already widely applied in biopharma processing and refractometers are nowadays used for monitoring applications such as fermentation, cell culture, vaccines, protein, blood plasma and enzymes production.

Refractive index is becoming a revolutionary method for creating fundamental process understanding. In addition, it is useful to investigate several process dynamics and chemicals interactions required for the design of cost-effective robust processes and control strategies that reduce product variability. The examples presented above are only a few, but there is no doubt the opportunities will grow, as the pharma companies start looking to the future and refractive index measurements are used to the fullest potential in pharmaceutical processing.

Learn More from Webinar

Want to learn more? Watch the on-demand webinar where we discuss the benefits of refractive index (RI) in development and production of active pharmaceutical ingredients (APIs). 
Read the questions and answers we received during the webinar.