West Pharmaceutical Services Inc. (West), headquartered in Exton, Pa., designs and manufactures pharmaceutical packaging and delivery systems for the healthcare and consumer markets. West produces components for the packaging and delivery of parenteral pharmaceuticals. The potential for particulate matter to have a negative impact on patient safety is a specific area of concern for these types of products. Controlling particulates throughout the manufacturing process is critical to producing high-quality container closure and delivery components. As a result, West has undertaken a rigorous laboratory design program to address these concerns.
Until late 2012, West had maintained a dedicated particle laboratory. That laboratory was capable of performing state-of-the-art particle testing under strictly controlled conditions. However, due to the age and configuration of the laboratory spaces, there were several limitations as to how that testing could be performed. The particulate level in the labs was well controlled, but to assure absolute cleanliness, West scientists were required to work in custom-designed laminar flow hoods. While these hoods were certified ISO 5 (Class 100) environments, working in such a constrained space put severe limitations on throughput and future growth potential.
West recently relocated its corporate headquarters to a newly constructed, 161,554 ft2 facility. The facility includes a 13,500 ft2 analytical laboratory wing with 1,700 ft2 dedicated to cleanroom capabilities. There are three cleanroom suite classifications on site: ISO 7 (Class 10,000), ISO 6 (Class 1000), and ISO 5 (Class 100). The cleanroom suite environments have fully automated monitoring systems that assure the concentrations of airborne particles within each suite meet specifications for the designated ISO classification. The rooms are monitored continuously for pressure, temperature, and relative humidity. Each ISO classification has a different function within the testing matrix of the analytical laboratory, accommodating the Filling, Microscopy, and Particle Laboratories. It is critical to have a minimum level of cleanliness in these areas to avoid cross contamination of the samples from the testing environment and laboratory personnel. To facilitate cleanliness and low particle load in the suites, the analysts have been trained in cleanroom procedures for gowning and operations.
The ISO 7 suites support West’s manufacturing facilities and client base for product investigations. These suites contain a JEOL 6490 Low Vacuum Scanning Electron Microscope with a Thermo Energy Dispersive X-ray detector, a Thermo Fourier Transform Infrared (FTIR) Microscope, and several other diverse optical microscopes that include several stereo light microscopes, an Olympus Research Compound Microscope with Differential Interference Contrast (DIC), and a Nikon Polarized Light Microscope. These analytical techniques are used for visualizing and measuring microscopic features and identifying unknown contamination. For example, there have been numerous product recalls over the last few years due to glass particles or flakes in vials of injectable drug product. The phenomenon, known as glass delamination, occurs when the surface of the glass container reacts with the drug product and facilitates shedding of glass particles into the drug product. West developed a method to look at the interior wall of glass containers using Differential Interference Contrast Microscopy. This method helps to screen glass containers for the propensity to delaminate. The technique is ideal for looking at transparent features that would, under normal optical inspection, be invisible. This method requires the microscope to be equipped with Nomarski prisms and a long working distance 20x objective.
One of the three Microscopy Laboratories located in an ISO 7 Suite at West’s new facility. Photo courtesy of West Pharmaceutical Services Inc.
The ISO 6 suite’s primary function is filling syringe barrels and cartridges (for engineering purposes) in a particle-controlled environment. Plungers are then inserted in these filled components using dedicated instrumentation specifically designed for this purpose. These filled components are used for internal stability and engineering studies in support of new product development by the R&D division at West. West also performs small- to medium-scale filling and engineering studies for its customers.
The filling suite is equipped with a Cozzolli and a KT filling instrument. These instruments place plungers in the syringe barrels and cartridges (1 to 5 mL) by vacuum placement. The Cozzolli is a continuous process design, and the KT places a single plunger at a time. The studies focus on functional and extractable testing. The specific functionality tests include sealability, break loose, and extrusion force. Sealabilty testing measures the seal integrity of the syringe or cartridge component, which is critical to sterility and leakage control. Break loose measures the force it takes to initiate plunger movement in a syringe or cartridge component, and extrusion is the force needed to keep the plunger moving until the syringe or cartridge component is evacuated. This testing is performed on an Instron using methods developed by West. Syringe filling in a typical manufacturing environment is always performed under strict particle control. That same control is equally critical to assure valid test results during engineering studies.
The Clemex Imaging System is the newest addition to the particle technology in the ISO 5 Suite. Photo courtesy of West Pharmaceutical Services Inc.
Particle Analysis Suite
The ISO 5 suite is designated for particle analysis (counting and sizing). Many of the developed particle methods at West are based on the USP, General Chapter <788> Particulate Matter in Injections, and ISO 8871-3 Elastomeric parts for parenteral and for devices for pharmaceutical use – Part 3: Determination of release-particle count. The types of samples tested are diverse and challenging. Samples can range from a very small 1 mL elastomeric plunger to a complicated 500-liter pharmaceutical drug container.
A few examples of particle counting and sizing techniques used routinely are PCI (Proved Clean Index), which is a filter membrane technique used for detecting visible particles greater than 25 microns; a liquid particle counting technique, HIAC, that uses light obscuration to detect particles from two to 400 microns; and Clemex Imaging System, which is a microscopy technique that also uses a filter membrane that can measure particles from five to greater than 400 microns. The Clemex Imaging System is a new addition to West’s particle laboratory in support of the ultra-clean product lines for Westar and NovaPure components. This technique uses an automated counting and sizing system that combines both sub-visible and visible particles into one method. An additional advantage of this technique is that it traps the particles on a membrane, which allows West to identify the particles and thereby trend processes and utilize that data for process improvements. This new, fully certified ISO 5 lab space allows multiple analysts to perform multiple critical particle analyses simultaneously while minimizing concerns about cross contamination.
West has many years of experience in the development of pharmaceutical drug packaging. With the addition of these state-of-the-art particle suites, West can assist its customers through the complex laboratory analyses associated with meeting drug product, stability, container closure and packaging regulatory guidelines.
Westar and NovaPure are registered trademarks of West Pharmaceutical Services Inc., in the United States and other jurisdictions.
Linda Lathrop joined West in 1977, and has over 30 years of experience in West’s Analytical Laboratory holding various positions of responsibility in support of Quality Control, Technical Support, and Customer Product Concerns. She has supervised the group since 2002. Linda’s experience includes various wet chemistry techniques, chemical, and physical testing for USP, JP, EP, British Standards, and ISO, as well as method development in support of new West products.
Paul Cummings has over 30 years of experience in the pharmaceutical industry. He is currently the Laboratory Operations Manager for West Pharmaceutical Services Inc. He has a very diverse background in analytical chemistry, with expertise in mass spectrometry. He has also managed a pilot plant laboratory for a major pharmaceutical company. Paul received his Master’s Degree in Chemistry from Villanova University.
This article appeared in the April 2013 issue of Controlled Environments.