Amber Lowry is an associate editor at UBM plc.

Amber Lowry

	Understanding the role of both people and technology in the maintenance of data integrity in the analytical laboratory is crucial as companies move toward predominately electronic systems. While technology has helped make the preservation of data easier, it is just as important that the people operating these systems are aware of the relevance of each step involved in the process, says Steve Hayward, product marketing manager at BIOVIA, Dassault Systèmes. Hayward spoke with 

 about what it takes to successfully maintain the integrity of data in the modern laboratory.

: What is most important to consider for lab data integrity?

: The people in the lab and the digital solutions they use play an equal role to ensure data integrity. Technology helps to make it easy to execute, as well as to proof integration. The technology of the past decade has allowed for better preservation of data, from the time of capture in electronic format through to its analysis and use in reports. 

	This digital thread of information can now be preserved throughout an organization, but it is critical that the people who use the technology are aware of why each process step is relevant, and adhere to them at all times.  Automation is also a key factor. The best way to ensure this consistency is by making it easier and less time-consuming to perform each routine activity, while passively recording each action for regulatory compliance. This can be achieved by automation-enabling technology.

: How can data integrity in the lab be improved by the use of electronic systems?

: Electronic data systems that automate data transfer allow for the reduction or even elimination of human intervention, and therefore, the reduction of errors. Audit trails will prove the integrity of the data or show the details of the change. This means any data alteration--voluntary or involuntary--will be either not possible, or any changes will be recorded so it will be obvious that data have been modified. 

: What are the data integrity risks associated with computerized systems and how can they be diminished?

: In the modern lab, it is a fact of life that there will be multiple electronic informatics systems, where the landscape’s complexity has usually scaled with the size and age of the company.  Data are constantly passed back and forth amongst these systems, and may be transformed during the process.  At each step along the way, the process must be validated to ensure that the integrity of the data, and the digital thread of information, is preserved. Recently, the trend has been toward consolidation of these disparate systems into more comprehensive solutions, where the data are stored in a single, centralized system and accessed as needed, without the need for constant transformation and transposition. While validation is still necessary, this removes both the day-to-day complexity in the lab and much of the risk of compromised data integrity.

: How can manipulation of electronic records be identified and prevented?

: In the lab, all data files should only be accessible through a software system which requires secure user login, and tracks all modifications as part of the audit trail. A computer’s operating system-level login is not sufficient for this purpose.  Although many solutions exist to enforce audit trails, in many cases, a user must log in to multiple different systems, sometimes more than once, just to complete a single task.  With ever-increasing regulatory requirements, routine tasks can take longer. A goal in the modern digital lab is to minimize the number of systems a scientist must use for any given tasks, which increases efficiency, centralizes the management of audit trails, and minimizes the potential for data corruption or manipulation.

: What can companies do to improve lab data integrity when using electronic systems?

: Many paper-based processes have already been eliminated from the lab during the first wave of digital lab solutions. However, the multitude of different electronic systems in place, often from many different vendors, means that data still must be transposed and often transformed as it moves from one system to the next. Each of these steps must be configured and validated to ensure both regulatory compliance and the preservation of the data’s integrity.  Where possible, systems should be consolidated to remove the multiple different data file types and connections between software from different vendors.  It is also of the utmost importance that users are appropriately trained on the systems, and that their qualifications kept up-to-date.

Articles

Steve Hayward, product marketing manager at BIOVIA, Dassault Systèmes, explores the significance of both new technology and knowledgeable personnel for maintaining data integrity in the laboratory. 

Data Integrity: Finding Balance in Today's Lab

With advancement in vaccine development comes an urgency to optimize the cold-chain delivery of these increasingly condition-sensitive biological products. This sensitivity has added new degrees of complexity to already complex supply chains and global regulations, resulting in the need for more precise approaches toward transporting vaccines. 

Pharmaceutical Technology and BioPharm International

Vaccine Development and Manufacturing 2017

	When referring to this article, please cite it as A. Lowry, " Cold Chain: Delivering Vaccines to Patients," 

Pharmaceutical Technology and BioPharm International Vaccine Development and Manufacturing 2017 eBook

This article explores some of the challenges, services, and technologies that go into ensuring that vaccines are properly temperature controlled and maintain product integrity for delivery to patients.

Cold Chain: Delivering Vaccines to Patients

	Over the past several months, manufacturers pushed technological limits to release products to optimize API and drug product manufacturing processes. Some of these technologies include advancements in lyophilization, continuous flow chemistry, process control, and powder handling. Below is an assortment of such products for API and drug product manufacturing.

	Telstar has developed LyoGistics Zero, a vial automatic loading and unloading system for freeze dryers with a contactless magnetic drive for the manufacturing of hazardous products (1). A steam-sterilizable slider uses a passive linear magnetic driving mechanism that functions without racks, belts, or bellows to reduce particle generation and improve cleanliness. The slider remains in the chamber and is cleaned and sterilized with the internals of the freeze dryer. The system is suited for aseptic isolators requiring advanced protection for the operator (Occupational Exposure Limit 5), product (ISO5), and environment.
	
	The Lyometrics system from Telstar provides online monitoring of global batch temperature during developmental or full production conditions in GMP industrial freeze dryers with automatic loading and unloading systems (2). With the use of soft-sensor technology, the system offers a more practical approach to collecting product temperature when production environments are presented with automation and physical obstacles. The software within the freeze dryer control system can non-invasively obtain the average sublimation interface temperature of an entire product batch.

	Titan, a modular continuous chemical processing system from Syrris, is a turnkey system for prolonged use in demanding manufacturing environments (3). It comprises a range of integrated, rapidly reconfigurable modules, enabling continuous flow processes to be performed on a laboratory scale, or at rates of up to a tonne per day. Reactors are available in 64 and 250-mL volumes and may be connected when larger-scale systems are required. The system offers high chemical resistance, and it can accommodate reaction temperatures from -40 to +250 °C and pressures up to 20 bar at flow rates between 1 and 250 mL/min per channel.

	The Dynatrol CL-10GP Proportional Level Detector controls liquid levels in pilot plants, pharmaceutical processing, and small vessels to obtain proportional level control over an exact range (4). The EC-103C(G) Control Unit is paired with the detector and can activate electro-pneumatic transducers, valve positioners, indicators, controllers, or other direct-current devices. The level detector and control unit monitor and control liquid level range using a high-resolution, proportional output signal. This control operates under varying frequency power supplies or harsh process conditions, such as high pressures and temperatures. 

	Malema Sensors added SumoFlo, a single-use flowmeter that measures flow rates from 50 gm/min up to 100 kg/min with accuracies within 1% of reading (5). Fabricated from gamma-sterilizable PEEK (polyether ether ketone), the device provides single-use flow measurement solutions for biopharmaceutical manufacturing applications including tangential and depth filtration, buffer dilution, cell cultures and cell harvesting, chromatography, and hygienic fluids with varying density or viscosity. Calibration parameters for each sensor are stored on a radiation-tolerant memory chip allowing the sensors to be interchanged with other SumoFlo electronics transmitter without affecting measurement accuracy. 

	SupplyCare 3.0 from Endress+Hauser is an update to its Industrial Internet of Things (IIoT) application for tank inventory management (6). The system provides an overview of levels and product inventory in tanks and silos worldwide. Features include hardware and software options allowing level, flow, and pressure data to be displayed at a desk or handheld device, as well as inventory tools. The system uses Connect Sensor FXA30, a battery-powered cellular gateway for remote monitoring of level, flow, and pressure instruments in locations where power is not available. IMS SXS70 Middleware enables the integration of accumulated data with enterprise resource planning or manufacturing execution systems. Hardware developments include Fieldgate FXA42, a gateway that acquires data from local-level flow and pressure instruments and sends it to the local control system, transmitting the data via an integrated web server. 

	Siemens’s Sitrans FS230, a digital ultrasonic flow system, consists of the Sitrans FST030 transmitter and Sitrans FSS200 clamp-on sensors (7). The system includes a digital sensor link that digitizes the signal at the earliest stage of measurement to optimize the signal-to-noise ratio. Because of the system’s 100 Hz data update rate and integrated algorithm, the transmitter detects small flow changes for rate accuracy of 0.5 to 1% and zero-point stability. The flow system’s patented pipe configuration menu allows the user to select various upstream pipe anomalies and automatically adjusts for flow profile disorders stemming from unfavorable upstream conditions. Other features include comprehensive diagnostics, mounting hardware, built-in startup wizards, and a customizable human-machine interface. Support tools provide direct access to all operational and functional data, certificates, and audit trails. Comprehensive diagnostics facilitate preventative maintenance. 

	Semi-automatic powder handling technology

	The JetBreaker system from ILC Dover is a semi-automatic powder handling system that deaggregates powdered media and buffer powders so that they can be better mixed in solution. Powders such as sodium chloride and ammonium sulfide may require delumping before dispensing into process liquids. According to the company, if the aggregates are not fine enough, they can damage process valves and equipment (8). Tests performed by the company found that the system produced homogenous powder while flowing through a feed hopper into the company’s jet venturi mixing systemat 1250 kg/h. 

	1. Telstar, “Telstar to Introduce to the US Market a New Loading/Unloading Solution for Pharmaceutical Freeze-Drying Processes Driven by a Contact-Free Magnetic Propulsion System,” Press Release, February 24, 2017.
	2. Telstar, “Telstar Integrates New Soft Sensor Technology to Monitor the Global Batch Product Temperature During Primary Drying in GMP Industrial Freeze-Dryers,” Press Release, July 4, 2017. 
	3. Syrris, “Syrris to launch Titan Continuous Processing Scale-up System at InformEX,” Press Release, April 9, 2017.
	4. Dynatrol, “GP Proportional Level Output Detector,” Press Release, May 11, 2017.
	5. Malema Sensors, “Single-use, Gamma-Sterilizable Flowmeters for Bio-pharmaceutical Applications,” Press Release, May 10, 2017.
	6. Endress+Hauser, “Endress+Hauser Releases SupplyCare 3.0 Tank Inventory Management Software,” Press Release, February 23, 2017.
	7. Siemens, “Digital Ultrasonic Flow System with High Accuracy and Noise Immunity,” Press Release, April 24, 2017.
	8. ILC Dover, “ILC Dover’s JetBreaker System Allows Rapid Mixing of Large Quantities of Pharmaceutical Powders,” Press Release, July 11, 2017.


	Vol. 41, No. 9
	September 2017
	Pages: s39-s40

	When referring to this article, please cite it as A. Lowry, " New Technologies Optimize API and Drug Product Manufacturing," 

Innovative new technologies released over the past several months seek to enhance bio/pharmaceutical development and manufacturing. 
