Live from PDA/FDA: 5 Key Landscape Takeaways

From packaging and manufacturing to higher public-sector salaries, how are FDA and industry rising to meet cell- and tissue-based product challenges?

It’s one (amazing) thing to create a cell-based therapy or device in a specialized research lab, but it’s entirely another to create repeatable, standardized manufacturing on a larger scale where cell growth and manipulation are involved. Source: NIBIB
It’s one (amazing) thing to create a cell-based therapy or device in a specialized research lab, but it’s entirely another to create repeatable, standardized manufacturing on a larger scale where cell growth and manipulation are involved. Source: NIBIB

What regulatory and logistics hurdles await the industry as cell therapies advance? What is FDA doing to facilitate drug development and approval?

These were some of the focal points of the opening session of the 2017 PDA/FDA Joint Regulatory Conference in Washington D.C. These issues may not have concrete answers yet, but there are certainly people in industry working on the next generation of problems—and packaging is not being left out!

1. What sorts of packaging will be needed for cell- and tissue-based products? Complex therapies and combination products, such as scaffolds with added autologous cells, will need highly specific handling instructions, from shock protection to temperature, fluid and oxygen levels. With live cells, these products will need to be delivered in much shorter timelines than standard dosage forms.

2. Scale-up/scale-out will be a challenge. Before companies get to the packaging stage, they’ll need commercial-grade manufacturing processes. It’s one (amazing) thing to create a cell-based therapy or device in a specialized research lab, but it’s entirely another to create repeatable, standardized manufacturing on a larger scale where cell growth and manipulation are involved. As Rosemarie Hunziker, PhD, of the National Institute of Biomedical Imaging and Bioengineering, says, “Cells are going to be the operative word,” explaining that it’s a challenge to obtain cells in a reproducible, sterile way. The cells must proliferate within the bounds wanted—without detrimental features like tumors—and transported in their own local environment. “Cells don't stay put unless you anchor them. Scaffolding is important. … Conditioning the cells with the mechanical and electrical stimuli that they face in the body makes them mature into the types of cells and organs that we’d expect,” she notes.

3D printing will come into play, as device developers figure out how to make scaffolds on the fly but also in conjunction with the cells so that the device is ready for use. Bioreactor development is also an important area that requires focus.

3. The good news is that organizations are already working on the manufacturing–level readiness to meet these needs—The National Institute for Innovation in Manufacturing Biopharmaceuticals (NIMBL) and the Advanced Regenerative Manufacturing Institute (ARMI)—by developing scalable processes for cell- and tissue-based technologies. 

Hunziker explains, “When people think about innovations in manufacturing, they think about airplanes, automobiles and IT, not biologics. But there is enormous opportunity for improvement in biologic products. NIMBL is very broad in its research, from improving process engineering for small molecules, through enabling production of biologics (like some antibodies and/or growth factors) that have been highly challenging, to forging the trail for new manufacturing processes for cell-based therapies. Such innovation requires new research in science and engineering, but another critical piece is the training of the next generation of performers, from the PhDs inventing the technology down to the techs working with the equipment.”

“American innovation has been world famous for decades, and this invention space is ripe for a cornucopia of benefits, both medical and economic,” she adds.

4. FDA understands the need for flexibility and human resources in approving novel treatments such as regenerative medicines. “It was easier when change was slow. With recent advances, it’s become a full-time job keeping up with scientific advances,” says Peter W. Marks, MD, PhD, Director of FDA’s Center for Biologics Evaluation and Research (CBER). In approving the recent CAR-T cell treatment, Kymriah, an important dialogue started. “FDA had to be flexible, and couldn’t specify a set number of cells, there had to be a range.”

Hiring the appropriate workforce is also key. Marks says that in a good job market, government jobs are not quite as attractive. “But we have the potential to make it attractive. We were given some new provisions by Congress” which include the ability to pay professionals with biomedical expertise higher salaries, above the civil service standard. Marks is hopeful that human resources in government can be improved, admitting that they can be “suboptimal” at times. (It took three tries to get his own hiring letter error-free.)

5. Tissue chips will teach us a lot about manufacturing. Lungs, livers and other organs on chips are useful in determining things like early toxicology profiles for a given drug. But they’re also powerful teaching tools in how to assemble implantable tissues and organs as well. By reproducing complex conditions and functions like those in the liver, researchers can learn valuable lessons in building the proper scaffolding, biomechanics and environmental conditioning.

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