Looking Outside Your Four Walls at GMP by the Sea

It’s challenging enough to use Quality Management Maturity (QMM) within your own facility, and keeping tabs on suppliers is an even steeper climb. But the clues Redica Systems uncovers in regulatory data allow life sciences companies to complement existing QMM metrics for a much more predictive and proactive approach.

“Most companies are using 50 percent or more external manufacturing,” says Redica Systems CEO Michael de la Torre at the 27th Annual GMP by the Sea meeting in Cambridge, Maryland, in August 2023. “But when you look at QMM metrics, they have maybe one-tenth the amount of analytics or metrics on facilities outside their four walls.”

What should really scare you is all of these inspections that the industry isn’t talking about.

 

When you read in FiercePharma about poorly managed sites shut down by the FDA, that’s not what should scare you, says de la Torre. “What should really scare you is all of these inspections that the industry isn’t talking about.”

“There’s a lot of, ‘Oh, my gosh! I didn’t know that!’ floating around in all of this unstructured data in the industry” in enforcement documents and elsewhere, de la Torre explains.

Sifting Form 483 Data

For example, in Form 483 observations analyzed and scored by Redica Systems, South Korean CMO Celltrion, Inc., showed glaring quality-related warning signs in 2015. Two years later, an FDA inspection of Celltrion torpedoed two Teva Pharmaceuticals biosimilars that the two companies planned to market, trastuzumab and rituximab.

Figure 1 | In this heat map of CMO 483 scoring by Redica Systems, Celltrion, Inc., showed clear quality warning signs during a 2015 inspection, two years before another inspection earned the CMO an FDA Warning Letter. Higher scores represent a higher risk of receiving a warning letter.

The Redica Systems approach works because it painstakingly collects, “cleans,” labels, and links together a huge amount of raw, previously unstructured data. In this case, that data is mined from FDA 483 forms using proprietary AI/ML tools including Intelligent Document Processing (IDP) that scour text — and even handwritten notes — for detail. Redica Systems then simplifies its analytics to score that data, and translates it into graphs and charts for easy visualization.

Figure 2 | Linking “everything to everything” is a key component of the Redica Systems data treatment — for example, allowing life sciences companies to scrutinize observations in enforcement documents received by a particular CMO site.
How does Redica Systems score individual observations? An observation receives a Redica Systems score of 5 for big issues, such as manipulating data or for lacking a quality unit.

“You don’t get a data-integrity observation without at least being a 3,” adds de la Torre. “‘Attributability,’ ‘contemporaneous’ — that’s all at least a 3. It’s applied consistently, and it yields some interesting results.”

Scoring by “Events”

Redica Systems also uses a blunter tool to reveal CMOs with issues — event scoring. “This metadata is coming from multiple different agencies,” says de la Torre, including enforcement information from agencies such as Health Canada, the European Medicines Agency (EMA), and the U.K. Health Research Authority (MHRA).

“Then you have events like mandatory recalls, import alerts, consent decrees, all kinds of the usual suspects there,” he says.

“And so then, putting it all together, we just score individual events,” de la Torre says. “For example, if you lose your GMP certificate from EMA, it’s a 40-point thing. And if you get a warning letter and an import alert, that’s 40 points — so, losing your GMP certificate is kind of like getting a warning letter and an import alert put together.”

On the other hand, a single 483 can score a small number of points, while an inspection with a favorable result yields a negative score.

Emergent BioSolutions, Inc., has a score of 93. “What does it take to get a 93-pointer on this scoring system?” de la Torre asks. “They got mandatory recalls, and they […] lost their GMP certificate from every regulator who bothered. And that’s what did them in. They basically torpedoed J&J’s Covid booster.”

Figure 3 | In the Redica Systems event-scoring system, Emergent BioSoluions received a score of 93 over a three-year period beginning in 2020. Issues at the CMO’s facility in Baltimore, Md., brought FDA enforcement that stopped production of the Johnson & Johnson COVID-19 vaccine in 2021

Look Outside Your Facility’s Four Walls — Today

With insights like these, Redica Systems customers can start to predict where issues might arise in CMOs — and elsewhere in the supply chain. With that understanding, they take positive, proactive steps to keep production running smoothly.

How can Redica Systems help you get a handle on your supply chain? Request a demonstration today!