By Ken Congdon
The business needs of the pharmaceutical industry are evolving. Over the past five years, breakthrough therapies for oncology and rare and orphan diseases have placed increased pressure on drugmakers to accelerate product development while reducing development costs. Meanwhile, with the rise of precision medicine, pharmaceutical manufacturers are now expected to quickly produce a wide variety of products at significantly lower volumes.
These new drivers are pushing many pharmaceutical companies to look beyond traditional batch manufacturing processes and begin experimenting with a variety of continuous and flexible manufacturing techniques. Pfizer is no exception. The pharmaceutical giant first began leveraging continuous manufacturing for select products in the 2008-2012 timeframe. However, recently, the company’s focus has been on adding even more speed and flexibility into the continuous manufacturing concept. The result is what Pfizer calls Portable, Continuous, Miniature, and Modular (PCMM) Development and Manufacturing.
With PCMM manufacturing, Pfizer partners with GEA and G-CON Manufacturing to produce prefabricated pharmaceutical manufacturing PODs. These PODs are essentially different components of a pharmaceutical continuous manufacturing line (e.g. processing equipment, control systems, cleanrooms) that are produced as separate modules and shipped to a central warehouse facility for quick assembly. For its initial PCMM manufacturing pilot, Pfizer had prefabricated PODs produced in Belgium and Texas respectively. The company then had these units shipped to its Groton, CT, warehouse for assembly and operation. Videos illustrating the general POD concept can be viewed here.
How PCMM Differs From Other Modular Approaches
At first blush, Pfizer’s PCMM initiative may sound a lot like other modular or flexible manufacturing approaches in play throughout the industry. However, according to Phillip R. Nixon, Ph.D., Pfizer’s Executive Director of Drug Product Technology & Innovation Lead, there are a few key characteristics that differentiate Pfizer’s PCMM approach from other modular manufacturing techniques.
“With other modular manufacturing approaches, many of the parts are pre-engineered and prefabricated, but in the end, they are basically assembled to be a fixed facility,” says Nixon. “Those units aren’t designed to be disassembled and redeployed for another purpose at a later time. Our PODs are. Furthermore, other modular units need to have HVAC and other utilities added to them upon arrival. Our PODs are self-contained and autonomous. They all have built-in air handling and utilities, so they can be quickly integrated. We believe these differentiators make our PCMM approach faster and more flexible than other modular continuous manufacturing models.”
PCMM Manufacturing Benefits
According to Nixon, there are several operational advantages to Pfizer’s PCMM manufacturing approach:
- Rapid Deployment — Complete manufacturing facilities can be deployed in less than 12 months using the PCMM model. This time period begins from the moment a pharma company decides it wants to deploy a new manufacturing facility and ends when the prefabricated PODs are received and assembled onsite. This deployment turnaround time is much faster than the two, three, or more years it typically takes to construct a fixed manufacturing facility.
- Affordability/Economies Of Scale — PODs can be assembled and deployed in inexpensive warehouse space, which reduces the site cost for a manufacturing facility. There is plenty of vacant warehouse space available around the world, or pharma companies can build new warehouse facilities relatively inexpensively.
- Redeployment — Unlike other modular manufacturing approaches, PCMM units can be disassembled and redeployed if business conditions change. For example, if a pharma company wants to quickly capitalize on an emerging market or upgrade technology, it can do so relatively quickly by pulling out specific PODs and replacing them with new ones. This inherent flexibility allows pharmaceutical manufacturers to accelerate the innovation cycle.
- Accelerated Time-To-Market — One of the initial applications of PCMM technology within Pfizer will be to transfer new chemical entity products from its R&D site to launch and commercial sites with virtually no scale up or tech transfer. This will enable the company to accelerate its process development cycle and time-to-market.
- Data Collection — The FDA has gone on record touting how data-rich continuous and flexible manufacturing processes are, but the pharmaceutical industry has yet to effectively harness this data for its benefit. Pfizer’s PCMM units are designed to collect a wide variety of historical and real-time data (e.g. PAT [Process Analytical Testing] data, process parameter data) and transfer this information to an industrial data center within the POD for analysis. Gaining a deeper understanding of the data continuous manufacturing processes generate is an area Nixon believes is “ripe for additional exploitation.”
Can POD Technology Revolutionize Pharma Manufacturing?
Pfizer formally launched the PCMM concept in September 2013. In about a year, the company worked with its partners GEA and G-CON Manufacturing to produce the prefabricated units for its pilot launch. These units were shipped to Pfizer’s Groton, CT, warehouse in early 2015 and were fully assembled and operating within a couple of weeks. Currently, the PCMM facility is going through the FDA’s site qualification and calibration process. Nixon admits this process is lengthy, yet he states that elements of the PCMM model can help accelerate steps of the regulatory approval cycle.
“Because PCMM units are prefabricated, we can actually have many of the qualification and validation exercises performed on each unit at the vendor location and not repeat this activity once the units are assembled at the final warehouse site,” he says. “Not only does this help accelerate these processes, but we believe it will help actually reduce the cost of validation over time because the practice will become somewhat standardized.”
Once approved by the FDA, Pfizer has some extensive experimentation planned for its Groton PCMM facility. “We want to put the equipment through its paces and gain additional process understanding,” says Nixon. “We plan to experiment with different formulations and run various materials with different properties through the system. This will not only allow us to run the PCMM equipment with a greater degree of confidence than we do now, but it will also provide us with the data necessary to refine our engineering and computational models.”
Ultimately, Pfizer hopes to start developing new chemical entities and products using the PCMM units by the end of 2015. However, the company’s vision for PCMM technology extends much further than its own enterprise.
“We’d really like to see PCMM technology become an industry standard that is used throughout the entire pharmaceutical sector,” says Nixon. “We’re hopeful that pharma companies can find a way to collaborate to form multi-company POD farms where different drugmakers share large warehouse facilities with a central utility spine and produce their own products using different POD configurations. Because each company would own the process and product inside each POD, confidentiality and proprietary corporate information would be protected. However, the shared infrastructure could help significantly reduce the overhead costs associated with pharmaceutical production as well as the regulatory approval cycle.”