In general, how has the productivity of parenteral manufacturing companies increased/evolved over the last 20 years and how much of this evolution is due to advances in lyophilization equipment and technologies?
It’s been said that armies are “prepared to fight the last war;” similar is true for the pharmaceutical industry. Medicines have historically been based around small molecule drugs, typically formulated into tablets or oral doses. Parenterals were either vaccines or small molecule drug formulations for intravenous administration. Due to advances in the understanding of cancers and diagnostics technology, many new drugs are developing in pharmaceutical development pipelines and are just starting to receive licenses from industry regulators. These new drugs are often large biological molecules, typically proteins or antibodies, which currently have to be administered parenterally. However, proteins and antibodies require different manufacturing capabilities to those used for small molecules.
Speaking in an interview in December 2016, Andrew Skibo,1 Head of Global Biologics Operations at AstraZenca/Medimmune estimated that the pharmaceutical industry was overcapacity and closing facilities for small molecule manufacture, and investing some $20B in biologics capacity. We’ve seen that much of this investment is directed towards single-use technologies. In addition, the latter stages of production, primary packaging, is now being done under full isolation.
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SP carefully follows developments we believe have impact on pharmaceutical development and manufacturing. The rise of new biological drugs and follow-on biologics, or biosimilars, has been a focus of our lyophilization work with research and development scientists.
Looking at the challenges in development and production of these products has led us to assembling a suite of tools that overcome these challenges, increase efficiency and at the same time enhance quality and safety.
Small molecule formulations and vaccines that are freeze dried have typically not required the advanced lyophilization technologies now available, therefore their adoption has been slow, but the data supporting their use has become more compelling with the development of complex, costly biological drugs, and pharmaceutical companies are now adopting them into development and production.
Over this same time period what has been SP Scientific’s mission? How is the company helping the pharmaceutical industry bring safe and effective treatments to market over the last 20 years?
SP Scientific has a broad-reaching product portfolio. Our inherent vision is to deliver confidence to our customers by providing a fully controlled process that, within SP we refer to as Mission: Control. With a commitment to integrated products and technologies that meet the ever-evolving needs in pharmaceutical primary packaging, we focus on vial washing and sterilization through filling, capping and, where required, lyophilization and external vial washing.
SP brings together four leading brands, comprising Hull production scale and VirTis laboratory and pilot scale freeze dryers with the LyoStar freeze drying development system, and PennTech aseptic filling lines to deliver on this promise. Acquisition and further development of these brands means that SP can now provide full aseptic processing lines, which ensure safe and effective product packaging for manufacturers, care givers and patients. For example, we have vial washers that effectively clean vials without stainless steel needles, thereby avoiding the risk of chipping glass. Our depyrogenation tunnels can guarantee the thermic cycle regardless of clean room pressure fluctuations and provide in situ particle monitoring in all zones including the hot zone.
The filling systems offer 100% weight control as well as net weight filling to ensure patients get the proper dosage.
SP’s efforts in support of the industry have been threefold: the delivery of systems for current production and laboratory needs; the development of new technologies and systems to meet emerging and future needs, some of which are coming to the market at this moment; and, perhaps the one that sets us apart, our on-going efforts in Lyo education. This includes monthly technical webinars presented by leading lyophilization scientists, hands-on training courses and other lyophilization events, all of which continue to see growing demand.
Specifically, what equipment/tools/expertise does SP Scientific currently offer to assist pharmaceutical clients to effectively scale-up and manufacture lyophilized products?
Scalability is essential for the modern pharmaceutical industry. Small molecule drugs are expensive, but their newer biological brothers are significantly more costly to develop and produce, typically coming from cell culture and in many cases undergoing some transformation; for example, having a cancer-treating agent linked to produce an Antibody Drug Conjugate. During development, product is often scarce and expensive.
SP has developed a package of tools in the form of equipment and technologies that provide “line of sight” in scaling up during the transition from development to production, and as importantly, scaling down. The tools comprise products such as the LyoCapsule™, a 7-vial development freeze dryer that performs like a much larger production dryer – saving preparation time and active ingredient costs. Equipment such as this enables data to be more easily scaled, and can be augmented with data from technologies like SP’s patented ControLyo® for ice nucleation on demand and the LyoFlux® vapor mass flow sensor, which allows non-contact inference of critical drying data such as batch average ice temperature. These technologies can be provided on all scales of lyophilizers, from LyoCapsule to our much larger LyoConstellation™ production systems.
The ability to scale up more efficiently from the lab is of course a great benefit, but it is also important to note how this same information can be used, should the process stray outside the original design space – such deviations as may occur due to an unforeseen power loss during production. In these events, scaling down the process from the production unit to the laboratory enables an event like a power outage to be investigated rapidly and inexpensively, to confirm whether the production batch may be kept and safely provided to the patient.
Looking ahead, are there any lyophilization products/services/technologies being developed now that will help pharmaceutical companies bring innovative products to the market? How will SP Scientific meet this challenge for its current and future clients?
The nature and formulation of many products currently being developed is quite different from those previously seen. A vaccine contains much water whereas many new biological drugs are complex formulations with high protein contents and can present a significant challenge when freeze drying. Indeed, some of these cannot freeze in a traditional freeze dryer, but can be developed through to production with use of our ControLyo ice nucleation on-demand technology. Without the ability to induce nucleation simultaneously and at a higher temperature, some products are not viable. In addition, we see that such formulations may require much more aggressive drying cycles than have been used before.
To that end, SP has developed a new range of high-capability small production lyophilizers that enable aggressive cycles to be developed with high drying temperatures and low vacuum levels – conditions that would cause a traditional system to “choke.”
The industry has a growing interest in non-contact measurement of key parameters of the process. This is driven by the rise of automation as the FDA mandates removal of people from the process to protect the product from the operatives, and also the development of highly potent formulations to protect the operatives from the product. Traditional monitoring tools do not lend themselves easily to automation. Therefore we see wireless temperature sensors being introduced to cleanrooms and production cells, and other non-contact measuring systems, such as LyoFlux® tunable diode laser adsorption spectroscopy (TDLAS) for which SP partners with Physical Sciences Inc. (PSI). TDLAS as executed in the PSI system provides accurate measurement of the number and velocity of water molecules leaving the product chamber. This mass flow measurement allows the inference of many critical data of the batch of drying product, such as end points, ice temperature and mapping of the design space for a given formulation.
