Forging industry partnerships to accelerate the uptake of continuous pharmaceutical manufacturing
June 3, 2024
GEA and its partners are leading the way toward smaller, more flexible continuous processing technologies that are transforming the future of pharmaceutical development and manufacturing.
It’s been many years since the US FDA launched its Pharmaceutical Quality for the 21st Century program in 2002, which represented a major springboard for the pharmaceutical industry to modernize its manufacturing infrastructure. The initiative encouraged the adoption of continuous manufacturing (CM) and inline process analytical technology (PAT) systems that facilitated the implementation — from R&D through to manufacturing — of quality by design (QbD) concepts into the complete product lifecycle.
Even with the backing of a major regulatory agency, however, getting a new manufacturing paradigm accepted by the greater drug production ecosystem is no small undertaking. It can be somewhat overwhelming at first, challenging and is often perceived to involve a huge magnitude of change. Yet, first impressions can be misleading!
With a continuous line running at a customer’s site for almost two decades, GEA Pharma & Healthcare has, from the very beginning, led the field with flexible development options that improve commercial-scale production and enable greater process understanding to be achieved with smaller quantities of material. Also, the company’s experience in pharmaceutical oral solid dosage (OSD) production technologies and continuous processing experience in other industries, such as chemicals and food, gives GEA an edge when it comes to supporting the pharmaceutical industry in this game-changing switch from batch to continuous.
At the heart of GEA’s fully integrated, powder-to-tablet CM solution is ConsiGma®. This complete portfolio of technologies is designed to transfer powder into finished dosage forms in development, pilot, clinical and production volumes. ConsiGma® includes systems for dosing and mixing raw materials, wet or dry granulation, drying, tableting, coating and quality control, which can be integrated in one compact production line.
GEA has not only been helping pharmaceutical manufacturers to evaluate, develop and optimize continuous processing techniques to enable them to bring new products to market faster, the company has taken a proactive stance in the industry and spearheaded several collaborations and partnerships that have championed the implementation of CM to highlight its many advantages.
For example, GEA, GSK, Pfizer and G-Con Manufacturing formed a consortium to design and build a modular, autonomous manufacturing environment for continuous OSD form production. Presented with the award for Best Technologies Innovation during INTERPHEX 2015 and subsequently receiving an ISPE Facility of the Year Award (FOYA) in 2016 for Equipment Innovation, this first-of-a-kind portable, continuous, miniature and modular (PCMM) system shortens the timelines involved in tablet production.
Innovators certainly took notice! Back in 2015, for the first time ever, the FDA approved a new treatment for cystic fibrosis (CF) that had been developed and produced using GEA’s ConsiGma® CM platform. Further approvals followed for an antiretroviral medication to prevent HIV/AIDS (2016), a drug to treat breast cancer (2017) and another CF medication (2018). What’s important to note, here, is that a single CM line can be used to process any volume of product — from small quantities for formulation development and design of experiments (DoE) through to clinical trials and full-scale manufacture. This speeds up time-to-market by eliminating lengthy pilot-scale steps, scale-up and tech transfer. Not only does this remove the need for further investment, regulatory agencies also sometimes grant fast-track approval (emergency designations) for CM-derived products. Given that it normally takes 10–15 years to get one new medicine from initial discovery through to regulatory approval, any timeline reductions are, literally, life saving.
More recently, while evaluating ways to further increase the value of their products and processes, Janssen Belgium realized that they were reaching the operational limits of their batch manufacturing technologies. As a result, the company embarked on a strategically ambitious project to implement an end-to-end CM line. “The unique advantages of introducing an end-to-end platform will help us to develop novel products that would not otherwise be possible,” commented a Janssen spokesperson. What’s more, for their aspirational approach to advancing CM, Janssen received the 2020 FOYA in the Process Innovation category.
Partnering to advance continuous tableting technology
In 2022, Hovione and GEA announced a strategic collaboration to advance continuous tableting and dispel the common myths that #GoingConti is both overly complex and too expensive. With their combined efforts, they aim to significantly increase the adoption of continuous manufacturing by providing enhanced capacity, flexibility, standardized equipment, improved quality and increased efficiency. In their time working together, they have already demonstrated how continuous manufacturing can evolve from a complex process to a more manageable system for most companies.
Hovione continuous direct compression line, Lisbon, Portugal.
Since signing the original collaboration agreement, the two companies have worked predominantly on two areas of the partnership: developing the technology and the joint promotion of continuous tableting. The collective aim is to convince more end users to ramp up the production of OSD forms using continuous tableting technology. Both parties are aware that this will improve their respective presence in the CDMO (Hovione) and equipment manufacturer (GEA) markets, but state that the focus remains on operators and innovator companies.
Trade show
ACHEMA 2024
In terms of advancing the technology, the first concrete example is a new continuous direct compression (CDC) machine from GEA called the ConsiGma® DC Flex (patent applied for). As might be inferred from the name, the key advantage is that it’s a more flexible system; it offers both high and low throughput functionality as well being able to operate in both continuous and batch mode. At the same time, Hovione and GEA have also identified several other technical developments that they would like to address, such as speed of changeover (from one product to another), cleaning times and significantly reducing the delivery times of the ConsiGma® DC Flex units. Yet, the key objectives of the partnership remain the same:
- to make standard technology solutions available that make product transfer from one system to another much easier
- offer increased capacity to manufacturers by utilizing test and development systems from both parties
Plus, in a move to augment Hovione’s current GMP production equipment for continuous tableting (both CDC and wet granulation), GEA has recently supplied a lab-scale feeding and blending system for research and development (R&D) applications. Installed in a high containment environment, it will complement GEA’s own non-GMP setup. It’s now possible for customers and sponsors to run R&D-scale feeding and blending trials in a facility that’s compliant with good manufacturing practices. As such, and in response to industry demand, the two companies are filling a gap in the market and helping drug manufacturers to get products to patients faster.
ConsiGma® Dosing and Blending Module
“We believe that continuous tableting can offer significant benefits to our customers, not only by expediting time-to-market and reducing development and manufacturing costs but also by improving product quality and sustainability. Through our collaboration with GEA, we aim to revolutionize the continuous production of oral solid dosage forms, making the technology more accessible and efficient for pharma customers.
Filipe Gaspar
VP Technology Intensification, Hovione
