How a digital manufacturing solution embeds quality into cellular therapeutics production

Right-First-Time and Right-On-Time Logistics

PROVENGE is made autologously, using a single patient’s cells to develop a personalised treatment just for them. The delivery of PROVENGE to each patient is time sensitive. Dendreon has less than a week to create a patient’s personalised treatment, which includes receiving patient blood components, processing them to create a course of treatment specific to the patient, and then returning the therapeutic to the patient for infusion.

Any slowdown in the production chain could result in the infusion not reaching the patient and potentially delaying their treatment with this life extending product. According to Dendreon COO Chuck Olson, the optimised in-house logistical effort that goes toward the time-sensitive coordination of patient apheresis, transport, cell processing, and delivery of PROVENGE back to the patient has been pivotal to Dendreon’s success as a cell therapy pioneer.

Having more time is what these patients need and Dendreon works tirelessly to help give them that. The processing of patients’ cells into PROVENGE from across the United States takes place in Dendreon’s two manufacturing locations in Seal Beach, California, and Union City, Georgia.

One Patient = One Batch Record

PROVENGE has helped to extend the lives of approximately 40,000 men, each of whom had three distinct batch records associated with their treatment regimen. That’s 120,000 separate batch records! Due to the specificity of the manufacturing process, each batch record could be hundreds of pages long, requiring a lengthy line-by-line quality review of the batch record before release. Add to that the disconnect data locked in paper causes between production and quality control, and you’ve got a lot of hurdles to overcome to get one infusion out the door.

Dendreon partnered with MasterControl to further embed quality into its manufacturing processes with MasterControl Manufacturing Excellence (Mx), enabling the quality team to catch any issues in real time and work together with manufacturing to find a solution. Using review-by-exception functionality, the quality team can pinpoint major areas at risk of deviation and standardise the review process, thereby helping to eliminate possible production delays

Nadeem Sheikh, Dendreon’s vice president of research and manufacturing sciences, said it all boils down to cohesiveness.

If there is a need for an investigation or a follow-up with a nonconformance, how do you do that? Thirty years ago, [it] would be [a] paper-based system, most likely,” Sheikh said. “Imagine trying to do an investigation of a live product such as ours that has to be released in a matter of hours, and a decision has to be made. Will a patient get the benefit of the product? Will that patient get treated? Something like MasterControl really brings in efficiencies and speed and allows us to make decisions much, much quicker.”

Most importantly, Sheikh said MasterControl allows Dendreon teams to share real-time data, as well as reporting and statistics.

“I can see something that’s happened in Seal Beach or our other facility in Union City in real time through the system up in Seattle,” Sheikh said. “My folks therefore can then collaborate with manufacturing [and] quality at both facilities and work together to either close these non-conformances or do a technical assessment or impact assessment.”

Finding a Better MES

Before implementing MasterControl Mx, Dendreon used a paper-based batch record system in their manufacturing facilities. Though they’d been very successful using a paper-based manufacturing system, taking their batch record digital was the logical next step to increasing efficiency, improving batch accuracy, and keeping the company at the forefront of cellular therapeutics. But, like many companies in the cell and gene therapy space, Dendreon’s manufacturing processes didn’t align with legacy manufacturing execution system (MES) solutions that are designed for automated low-mix, high-volume production. Dendreon required something different – a solution they could tailor to their needs and would support their product development.

Director of Manufacturing Kyle Jackson said Dendreon wasn’t looking for an MES in the traditional sense.

“Our product is very manual, so we weren’t looking for a software that can control machinery, pumps, so forth,” Jackson said. “We were really looking for a paper documentation system in an electronic format.”

Jackson also noted that they were looking to remove paper from their cleanrooms to further ensure product safety.

Keeping paper batch records in the cleanroom is expensive and contaminationand error-prone, not to mention time consuming. It requires a copious amount of expensive specialised paper materials designed to be sterilised and brought into a cleanroom. Handwritten value entries are prone to mismarks and legibility issues. Communication between teams is delayed, and after completion, production record preservation requires the utilisation of expensive onsite storage. Changing to a digital solution has enabled Dendreon to resolve these kinds of compliance management and batch record inefficiencies.

MasterControl Mx takes away the burden of paper from Dendreon by providing electronic batch record documentation, giving both the manufacturing and quality teams access to in-process batch records, from start to finish, from any of Dendreon’s locations.

“The goal for the [Manufacturing Excellence] implementation at Dendreon was really twofold. It was one, to get paper out of our clean rooms. Secondary to that was really streamlining some of the processes associated with batch management, issuance review, and closure. We’ve been able to cut those down by almost 50%.”

Continuing the Digital Transformation

Dendreon’s experience with Manufacturing Excellence has been so good, they recently implemented MasterControl Quality Excellence, wanting to streamline their quality management system (QMS) and integrate training with manufacturing execution.

“We’re excited about moving away from the old systems,” said Chief Operations Officer Chuck Olson.

Olson, a 30-year veteran of biopharmaceuticals, has seen firsthand how difficult it can be to get employees on board when implementing a digital QMS. But he says that hasn’t been the case for MasterControl Quality Excellence at Dendreon.

“It’s one of those situations where people are excited to implement a QMS. That hardly ever happens, you know. Normally, it’s like pulling teeth, but in this case, we’re already electronic.”

Olson emphasised the positive response from employees he’s witnessed interacting with the new QMS.

“We have a [MasterControl] test system where people are able to go in and you hear comments like, ‘This is much better. This is easier.’”