You can’t get very far into a discussion of the modern-day pharmaceutical landscape without hearing the word “flexibility.” Gone are the days where it was common to find companies relying on blockbuster stars, produced in large quantities in dedicated facilities. Many of today’s specialty medicines are produced in higher potencies and smaller quantities. While the price tag may be bigger than traditional drugs, the complexity and business risk of manufacturing is also greater.
Priorities have shifted, and pharma manufacturers are stepping up their focus on increasing efficiencies and maximizing utilization in facilities. Contract manufacturers, however, are veteran players in this department. The nature of their business means juggling multiple clients and products while simultaneously delivering impeccable quality on tight timelines. Flexible production capacity, fast campaign changeovers, and rapid production at different scales are all part of the business model. Combine those demands with tight margins, and efficiency becomes a matter of survival.
Whether it’s a business necessity or a chosen mindset — or a combination of both — contract manufacturers have flexibility coursing through their veins. Insight into the methodologies, technologies, and strategies that today’s contract manufacturers are prioritizing can benefit the entire pharmaceutical industry as it enters a new era where flexibility is king.
Client and project diversity means equipment needs to not only be of the highest quality, but also serve more than one purpose. At Avista Pharma Solutions, a contract development, manufacturing, and testing organization with three U.S. sites, this flexibility is prioritized during equipment selection.
“We make sure all our equipment has the ability to fulfill a wide spectrum of formulation capabilities – from easy simple blends all the way to coated multi-particulates, for example,” notes Rich Shook, associate director, Drug Product Operations at Avista.
This flexibility extends to validation as well. Per the FDA’s process validation guidance, an Installation Qualification (IQ), Operational Qualification (OQ) and Performance Qualification is generally performed for each piece of manufacturing equipment. Completing these qualifications means that the equipment can then be used for GMP manufacture of multiple products. This serves to ease the transitions for customers looking to move from early formulation development to larger scale production.
Using the same equipment for multiple products also introduces safety issues for workers and, ultimately, patients. When it comes to selecting equipment, especially with the increased use of highly potent active pharmaceutical ingredients (HPAPI), contract manufacturers prioritize equipment that both provides containment — lessening the chance of employee and environmental exposure — and minimizes contamination risks.
In order to reduce the chance of contamination, establishing a cleaning validation process is critical, and these too must be flexible enough to cover the wide range of equipment used across various contract facilities. Most guidance documents encourage the use of a risk- and science-based approach to cleaning validation.
“Our analytical cleaning methods are validated to cover each of the materials of construction found at our facilities i.e., glass, hastelloy, stainless steel and PTFE. Swab and rinsate samples are tested at every product changeover with individual cleaning limits based on established allowable daily exposure calculations. This provides the analytics needed to rapidly move a product from one production area to another,” says Dave Rippon, manager, Project Management at Cambrex’s Charles City, Iowa facility. Cambrex is a global CDMO with API development and manufacturing facilities in the U.S., Sweden, Italy, Estonia and Germany.
Many contract manufacturers are reducing contamination risks by investing in single-use equipment. With clear advantages in terms of flexibility, reduced cleaning resources, and lower utilities costs, single-use equipment speeds changeover between products and batches and, in the context of a multi-product facility, can drastically lower the risk of cross contamination.
Just last year, Emergent BioSolutions, in partnership with the federal government, spent $80 million to double the size of its plant near Johns Hopkins Bayview Medical Center. Emergent is a global life sciences company that manufactures specialty products that address intentional and naturally occuring public health threats, as well as provides contract manufacturing services for both bulk drug substances and sterile injectable drug products. Emergent’s recent expansion included the purchase of an ABEC 4,000L Custom Single Run (CSR) bioreactor. This is the largest single-use bioreactor size available in the industry by a factor of two.
The use of single-use bioreactors (SUBs) in the commercial market is a relatively new concept, but Emergent BioSolutions believes it is going to be a major factor in the future of manufacturing.
“The use of SUBs saved us a significant amount money on upfront capital installation of cleaning systems and the ongoing operational burden of utilities, as well as enhanced overall flexibility of our facility. We can now turn over the facility in a matter of one week and have the speed and assurance of no contamination,” says Sean Kirk, senior vice president, Manufacturing Operations, Contract Manufacturing Business Unit Head at Emergent.