Harmonizing technology across the pharma lab and production floor

Historically in the pharma industry, different methods were employed in the lab versus in production to measure characteristics such as pH, conductivity and dissolved oxygen. This was a result of instrumentation geared more for one environment or the other across a variety of vendors and sensor technologies — but the practice of mixing methods between these two settings often led to discrepancies.

This and other measurement issues can be resolved by standardizing the technology used throughout the product life cycle, from process development to pilot to full production. And with modern developments in electronic sensors, the same instrumentation types can be used in the lab where stringent tests must be conducted to ensure quality, and in production where fast and accurate measurements must be made to keep operations on schedule.

By standardizing and using the right instrumentation throughout a product life cycle, measurement discrepancies and subsequent production and business procedural disruptions can be reduced. This article will examine some of the problems encountered in the pharma industry when using different technologies in the lab versus in production, and discuss how modern digital electronic instruments for liquid analysis can solve these issues.

The need for reliability and consistency

As process analytical technology (PAT) becomes more widely implemented throughout facilities, there is a growing need for proper instrument lifecycle management in the lab and production environments. By using digital sensor technology, the best practices used for instrument life cycle management in lab environments can be extended to instruments used in pilot plants and production environments.

Process analytical technology is driven by the U.S. Food and Drug Administration to design, analyze and control pharmaceutical manufacturing processes through the measurement of the critical process parameters affecting critical quality attributes. PAT aims to improve production by defining the critical process parameters, monitoring these variables in real time, and using the measurements to ensure quality.

The goal of PAT is to develop processes that consistently generate higher quality products, while improving efficiency through increased automation, reduction in cycle times, and uninterrupted batch and continuous processing. Such processes minimize rejection of products, thus improving efficiency.

Uninterrupted processing also improves energy consumption, material usage and capacity, generating significant benefits by improving the coordination of instrument sensor management among lab, research and development and production environments.

PAT is being implemented across the pharmaceutical industry, with a heavy reliance placed on the sensors used to monitor variables deemed critical to product quality in the production process. This need for advanced sensors in production environments does not take away from the need for lab-based sensors but instead drives the need for a common best-practices approach for both lab and production sensors.

With digital sensor technology and lab-based sensor life cycle management tools, the same sensors in the lab and production can be managed using the same approach.

Modern solutions for liquid analysis

Advanced instruments include self-diagnostic features, providing users with device health and calibration information, in addition to primary and secondary process variables. Paired with waterproof,  inductive electronic technology, these types of smart instruments are revolutionizing liquid analysis for lab and production settings.

Digitally-enhanced sensors are useful for measuring pH, conductivity, dissolved oxygen and other properties. Newer pH probes use specially designed glass membranes to enhance performance, and reference gels that improve measurement accuracy and decrease sensor degradation rates in harsh operating conditions, such as extreme temperatures, clean-in-place, steam-in-place and autoclave cycles. These devices convert a measured process value to a digital signal, and then transfer it inductively to a transmitter, with the sensor/transmitter pair constituting an instrument.

This technology eliminates problems associated with exposed metal and moisture effects, such as corrosion, ground loops, electrical interference, and more. The flexibility of its application in both mounted and handheld probes makes these sensors ideal for permanent or spot measurements in virtually any location.

New electronic sensor technology can store calibration information directly on each device, making it available for consumption alongside sensor diagnostic and process data. The technology provides detailed process review and trend identification, precise data management, and a basis for predictive maintenance and industrial internet of things services.

Non-contact digital data transmission eliminates the effects of moisture and corrosion, and galvanic isolation ensures interference-free measurement and electromagnetic safety. Many of the transmitters communicate via multiple digital fieldbus protocols for simple integration with existing equipment in the lab, and with control systems on the plant floor. 

Applications

Processors can improve measurement reliability and reproducibility with electronic sensor technology because inductive signal transmission is not prone to the same breakdown and drift associated with metal-to-metal connections. This makes these sensors especially suitable in SIP environments, where temperatures regularly reach 248 F or higher, and moisture is a concern. While conductive sensor/transmitter instruments may succumb to these harsh conditions over a short period, modern electronic instruments can last many times longer through numerous SIP cycles (Exhibit 1).

 Additionally, real-time diagnostics and health data make it easier to manage these sensors, facilitating proactive cleaning and calibration schedules because diagnostics can preemptively alert staff when service is required. Pre-calibrated sensors with inductive connectors make onsite exchange easy, enabling plug-and-play handling to increase process uptime.

An example where these benefits are apparent can be found in a four-pole conductivity sensor, using four conductors to measure conductivity. This design allows the sensor to operate over a broader measurement range than traditional two-pole conductivity sensors, while providing increased diagnostic data. The digital sensor head digitizes measurement signals and performs several internal instrument health checks, providing a host of performance and diagnostic data, in addition to process information.

With digital sensors and transmitters in sync throughout a facility, data can be easily communicated among lab, process, a host control system, and on up to the enterprise level. Data is no longer limited to the primary process variable, but now includes secondary process variables, sensor health, sensor performance characteristics, calibration information, and real-time diagnostics. All this information can be used to improve processes, optimize an instrument’s performance, extend its life, and maximize the productivity of operations and maintenance personnel.

These digital-based devices and systems are being further transformed with the industrial internet of things, taking the industry to places unimaginable at a time in the not-too-distant past.

The transformation of pH optimization

Historically, pH measurement systems — and their associated sensors — were applied specifically for use in each unique environment. pH measurement systems used in the lab were managed in the lab, while those used in pilot plants and on production lines were governed separately.

For example, an analog-based pH measurement system must be managed at its point of use with the sensor, cable, and transmitter calibrated together (Figure 4).