From The Editor | April 29, 2021

Standards For New Technologies: Easy Listening For Outsourcing


By Louis Garguilo, Chief Editor, Outsourced Pharma


We’re comforted by our music standards, those go-to playlists we can always rely on.

In drug development and manufacturing, standards are also music to our ears.

And the U.S. Pharmacopeia (USP) might be our industry’s top performer. That “group” has created our standards for generations.

Now, says Ronald Piervincenzi, USP’s CEO, advanced technology – particularly continuous manufacturing – needs new standards to guide the next generation of U.S.-based production of medicines.

In this second part of our interview with Piervincenzi (part one is here), we’ll consider:

  • Outsourced Pharma readers increasingly rely on external partners for the execution of your business models for asset development and manufacture
  • To enable more domestic outsourcing options, CDMOs need advanced capabilities, whether in the realm of cell and gene technology, ADCs, MAbs, or even generics
  • Therefore, our generational challenge includes working towards this implementation of new technology platforms, capabilities, and capacities, at your CDMOs

Piervincenzi has set his organization to doing all it can to accomplish the above, and promoting those efforts and results.

“The CDMO industry is hugely important in this objective of creating standards and increasing domestic, advanced manufacturing,” he says.

Listen To The Music

“Everybody involved in the manufacturer of drugs can contribute to our standards creation,” Piervincenzi explains.

“Today, CDMOs increasingly add to process and production decision-making, and create methodologies for biopharma clients. They're playing a partner role.

“That makes CDMOs even more important as we look to create standards to drive that innovation, and profitability.

So what does that actually mean for advanced technology?

“CDMOs help establish an experience base, and proof of new concepts the USP can then begin to utilize for standards creation to apply throughout the industry.

“As we’ve discussed before, over the course of time this will result in a lower cost of production, and facilitate domestic production in the U.S. as well.”

How about the regulators acceptance of advanced technologies?

“It’s not a hard case to make if you've proven they work. We’ve have been able to create standards that increase both client and regulatory confidence and acceptance.”

Background Singers?

Embarrassed yet unabashed, I relay to Piervincenzi my experience working at a global CDMO, in my case in business development.

“In all those years, I can’t remember hearing much of anything about the USP,” I confess.

“Where is the USP in terms of impact and actual communication between CDMOs and the USP?

“The FDA and other regulatory bodies show up to inspect our facilities and make suggestions. As do most our customers – and they have their own “standards” ideas we need to address. Of course we have our own rigorous quality and management systems as well.

“I don't know where the USP fits in."

Piervincenzi replies: “We are within all those things you mention.”

“In those standards your CDMO follows – not the product specific standards – but all the general processes for how you manage your data, how you run your analytical equipment, the QA and QC labs. Your scientists and engineers follow USP all the time.”

Consider the easy example of a Prednisolone steroid pill, he suggests.

“Working backwards, you have the finished dose where there’s a specific dissolution test you must run to make sure the product dissolves, and that it releases the drug at a specific rate, in the right amount of time. That's a USP test.

“You then move up to where you had to look for impurities; USP test, and USP specifications.

“You go to the manufacturer of that Prednisolone, let's say it's a CDMO, which it probably was. It looks at the ingredients, the excipients, the API, and for each of those, there are USP standards and monographs informing what should be there, and what shouldn't.

“There are the important general methods: How do you insure your equipment is calibrated properly? How often do you calibrate? So you can imagine there are literally hundreds of these.

“All this happens routinely. It doesn’t come up to someone who was in your position.”

Nice of him to add that, but I can see that to some level, the importance of these standards should reach everyone at the biopharma and your CDMO. Particularly when we get back to the subject of adapting advanced techniques and technologies.

And something else of importance chimes in.

Price Of Admission

Everything has its price.

Who pays to purchase and install ‘advanced” equipment at CDMOs? Where do the dollars come to refit labs and plants, train workers, etc.?

These aren’t questions Piervincenzi or the USP can answer directly.

However, costs are a serious consideration for the organization when creating industry standards.

“Of course the companies we partner with deal with costs all the time,” he says. “They give us feedback. We are responsive.”

“But one of the associated costs is not having standards.” (see part one)

“We know good standards reduce costs. So you could say we're indirectly involved in costs a lot, whether we like it or not.

Piervincenzi offers an example.

“There’s almost always a more sensitive technique that can give you even more accurate measurements of something.

Actually, an important part of our work is finding out what can work in practice, and also providing ‘multiple choices,’ meaning offering a couple of techniques that you can use.

“There are nuclear magnetic resonance techniques that can be amazingly sensitive for detecting impurities. But if everybody had to use NMR on every single project, we’d all be bankrupt.

“Practical choices usually present themselves in some obvious ways.

“Consider the heparin adulteration scandal, in which many people died. So now NMR is embedded in our standard for heparin, because it's the only way to detect the adulterate – it’s the only way to ensure the right answer.

“But we didn't add it to every single standard – it would create a huge cost for everybody, for marginal or maybe no benefits overall.

“So costs are always part of our thinking.”

And on that note, let’s conclude our two-part discussion with USP CEO Piervincenzi.