LSNE (a PCI Pharma Services company) uses digitalization to ensure quality, compliance, and data integrity

(Photos: Lyophilization Services of New England, Inc.)

(Photos: Lyophilization Services of New England, Inc.)

(Photos: Lyophilization Services of New England, Inc.)

Lyophilization Services of New England, Inc. (LSNE now part of PCI Pharma Services) is a contract manufacturer and developer (CDMO, Contract Development and Manufacturing Organization) that provides services to pharmaceutical, biotechnology, and medical device companies worldwide. In addition to a range of contract manufacturing services, LSNE specializes in cGMP applications for aseptic filling and scale-up of lyophilization.

LSNE includes five FDA-inspected facilities in the USA and Europe, with a sixth facility opening in 2022. To support commercially approved medical devices and pharmaceuticals in over 30 countries across North America, South America, Europe, Africa, the Middle East, and Asia, LSNE's services are divided into three categories: development, manufacturing, and analysis. With the acquisition by PCI, the merged companies now offer globally integrated, comprehensive CDMO services for customers, including development and manufacturing, clinical trial services, and commercial packaging.

LSNE's services include formulation procedures for emulsions, suspensions, liposomes, polymer nanoparticles, or lipid nanoparticles (LNPs). At the same time, the company is industry-leading in lyophilization (freeze-drying), a process of stabilizing biological substances through freezing and sublimation of frozen water from the product under high vacuum. Products that degrade in solution, which applies to most pharmaceuticals or biological products, benefit from lyophilization to ensure product efficacy and extend shelf life. The use of heat to remove moisture would degrade many products. Instead, lyophilization uses freezing conditions under vacuum. With more than 30 freeze dryers worldwide, LSNE is currently one of the largest service providers in the industry.

Daniel Gabrault has been a plant engineer at LSNE for over three years. Currently, he is responsible for overall support for facilities, systems, utilities, and equipment. When he started at the company, there were various monitoring systems distributed across the facilities. In 2018, LSNE decided to standardize environmental monitoring of individual facilities with the continuous monitoring system Vaisala viewLinc.

Monitoring multiple parameters

"Initially, we had Vaisala perform the installation and validation for system deployment," recalls Daniel Gabrault. "After many years of using viewLinc, we find it easy to expand the system ourselves."

Vaisala offers protocols for Installation Qualification (IQ) and Operational Qualification (OQ) to simplify validation. Daniel Gabrault was able to further optimize the documents for simplicity. "I used the data from Vaisala's IQ and OQ and adapted it to our requirements. I simply record the location, serial numbers, alarms, and functions, and the validation is straightforward."

Once the viewLinc system was installed and validated, LSNE could monitor multiple environments, including walk-in or accessible freezers and refrigerators, as well as cleanrooms. For most applications, VaiNet wireless data loggers (the RFL100) are used.

"I highly value the RFL100 wireless data logger because it is easy to place and configure," says Daniel Gabrault. "The RFL100 also has a digital display, so we can quickly check conditions and determine if the device is functioning properly."

The viewLinc system can also be easily standardized across applications.

"It was important for us to have as much environmental data as possible in one system," says Daniel Gabrault. "So we use other devices in viewLinc to obtain parameters not currently included by the RFL100 logger. Additionally, we use the Vaisala CAB100 in our cleanrooms to monitor ambient temperature, relative humidity, and differential pressure."

The Vaisala Industries Cabinet CAB100 integrates multiple sensors into a simple pre-configured instrument panel. While typical parameters include differential pressure, ambient temperature, and relative humidity, the CAB100 can also accommodate a variety of analog inputs that can be intrinsically safe.

"In the case of the CAB100, based on previous experience with cleanroom monitoring systems, I estimate that most systems would take up about four times the space of the Vaisala CAB100. Its small footprint and pre-configured nature make it very practical."

"We also use universal data loggers DL4000 for parameters such as pH in waste management monitoring. With these measurements in viewLinc, we ensure compliance with local environmental regulations."

Monitoring GMP compliance

To ensure the highest quality for customer companies and patients, LSNE must undergo regulatory inspections by various authorities and conduct numerous audits for customers and qualified persons. These regulatory reviews require the company's quality systems to be up-to-date, compliance-oriented, and continuously maintained.

"Recently, our focus has been on customer-specific audits. Every time one of our clients receives a new drug approval, the FDA comes into play for that client. Since our clients seek FDA approval, the FDA must investigate everything related to the submitted product."

"Our clients also review our quality systems," explains Daniel Gabrault. "During these audits, our clients appreciate the monitoring capabilities of viewLinc. The system provides data on all environments whenever they request it."

In 2016, the FDA published a draft guidance on data integrity stating: "In recent years, the FDA has observed an increase in cGMP violations related to data integrity during cGMP inspections. This is concerning because ensuring data integrity is a key part of the industry's responsibility to guarantee the safety, efficacy, and quality of medicines, and it supports the FDA's ability to protect public health."

"Data integrity is extremely important to us," emphasizes Daniel Gabrault. "In viewLinc, the Audit Trail ensures that no data can be altered. Even if the unit or device is deleted, the data remains permanently stored, which is ideal for GMP. Yes, it can sometimes be challenging—for example, every incorrect password entry is recorded. Nothing can ever be deleted. But we need this kind of data integrity and access control for GMP."

Monitoring with flexible, reliable alerting

The viewLinc system can send notifications in various ways, including email, SMS, voice calls, light and sound signals, and relays to external systems. This allows administrators and users to receive remote alarms for areas under their responsibility.

"Currently, most alarms are sent via email, but we have also set up direct delivery of important alarms to mobile devices," describes Daniel Gabrault. "Some users have configured their settings to receive both emails and text messages. The system sends alarms immediately and without data loss when thresholds are exceeded or communication failures occur."

Daniel Gabrault also appreciates the reporting features of viewLinc. "The alarm report is particularly useful. You can easily generate a report only on the data you need."

Monitoring software for users

"The viewLinc system offers the best user-friendliness of all monitoring systems I have worked with. In other systems, I sometimes had to manually back up data, but with viewLinc, that's unnecessary. It's also very frustrating when the system crashes and you don't receive a notification. I've also seen monitoring devices that are overly large, which can mean extra setup effort."

The viewLinc software is designed to be easy to learn. The user interface is intuitive, with embedded prompts and functional "tours" to guide users through common tasks and provide instructions on the display as well as embedded quick info.

viewLinc tours

"It seems to be popular with everyone," says Daniel Gabrault. "It is easy to learn. We conduct an initial training, and this one-time training is sufficient. From then on, users can create their own reports and view only the data relevant to them. As a viewLinc administrator, I isolate all data so that employees only see the applications that are critical for them."

Vaisala also offers calibration options to ensure sensors maintain their accuracy, including Vaisala Service Center calibration, probe exchange service, or software and device calibration for internal use.

"We have a calibration team as part of our technical group, so we calibrate our sensors in-house," says Daniel Gabrault. "We use Vaisala MI70 to calibrate the RFL100 probes. The ability to calibrate internally definitely contributes to the user-friendliness of the system."

Scalable, standardized, and secure

The viewLinc monitoring system was designed to be easily scalable, a feature LSNE has utilized. "We currently use hundreds of devices across seven facilities—soon to be eight. I like that I can see what’s happening at our facility in Madison, Wisconsin, from my location in New Hampshire."

"Before installing viewLinc, different monitoring methods were used in several buildings," recalls Daniel Gabrault. "Some used chart recorders or older systems. viewLinc provided us with a single centralized solution."

Daniel Gabrault appreciates the user-friendliness and flexibility of viewLinc. At the same time, the remote alarm capability of viewLinc is its most important feature. Alarms ensure that products are protected around the clock from conditions outside specifications.

"In terms of alerting, viewLinc is relentless. The alarm persists until it is acknowledged."