Let’s Modernize Manufacturing

Current pharmaceutical manufacturing approaches are not without issue – and someone who knows of the problems all too well is Janet Woodcock, Director of the FDA’s Center for Drug Evaluation and Research. After all, as she puts it, regulators such as the FDA are the ones dealing with the consequences all of the time.

Woodcock spoke at the recent International Symposium on Continuous Manufacturing (ISCMP), held in London, offering the FDA’s perspective on the need to modernize the manufacture of pharmaceuticals. “Technology has transformed to allow continuous processes to exist and they have existed for a long time. Traditionally, the perception of risk, including regulatory risk, initial investment and the sub-costs has limited uptake,” said Woodcock. “Evolution in science and technology will drive the need for new methods. The technology available has been used in other sectors and the regulators are on board.”

Today, the time to build and qualify new facilities, time and cost of scale up, repeated need for off-line laboratory testing steps, and the inability to use modern process control methodologies are key problems in the pharma industry. In addition, the timelines for pharma development are no longer acceptable – the industry can’t take 7 years to figure out how to make a final product at the commercial scale. Patient populations have changed too; companies will likely find themselves increasingly making multiple expensive drugs for small target populations.

One of the key technologies discussed during the presentation was continuous manufacturing, which may offer a number of advantages. For small-molecule finished dosage forms, Woodcock’s presentation listed the followed as potential advantages:

• Faster scale up with fewer surprises
• Less environmental impact
• Ability to respond faster to increasing demand
• Potential for regional hubs and less convoluted supply chains
• Possibility of novel dosage forms. For example, do excipients have to be used? Do all drugs have to be capsules and tablets? Could APIs be printed, sprayed or injected?

“The FDA has approved four drugs using continuous methods with finished dosage form. So, at the moment, we do have a number of commercial products produced by continuous, and we expect more  – and we continuous API synthesis, like crystallization, submissions from both generic and innovator sectors in the next year,” said Woodcock. However, also stressed that the use of continuous will not be a method to shut out generic or biosimilar competition – and regulatory authorities will be paying attention to this. Woodcock also acknowledged that not all products will have a business case for implementing continuous.

Other transformative methods in the manufacture of medicines were also touched upon. “Some people within the US government – not at the FDA necessarily – envision pharmacy on demand where the patient goes to the pharmacy, they punch in their needs, and the medicine is synthesized there, perhaps printed on a film [...] Certainly, the military would like to see this happen; on-demand pharmacy on the back of a truck in a war zone would certainly revolutionize the treatment of patients. These are the people who are thinking about how the future ought to be.”

The FDA has an emerging technology team to help ease the path of innovation and is also collaborating within the Federal government, and with industry, academia and consortia. It has also established the Center of Excellence in manufacturing Science and Innovation to understand the challenges in downstream bioprocessing (especially viral clearance), to explore validation of advanced analytical platforms, and look into process modeling and simulation in regulatory risk assessment.

In terms of policy advances, Woodcock explained that the ICH has accepted the FDA’s proposal for new guideline development for continuous manufacturing, and the US Pharmacopeia has also established an expert committee on continuous manufacturing to identify potential opportunities for standards.

Clearly, the business of making medicines is changing. “There are new demands, such as drugs for victims of terrorism, war, and natural disasters; the need for supply redundancy is going to require more agility and flexibility in manufacturing than we currently have. And the stakeholders, governments, healthcare systems, and public health authorities are going to call upon you to deliver these things,” said Woodcock.