White Paper

Digitizing Your Clinical Process: The Why and How

Learn why manufacturing execution systems are uniquely suited to clinical manufacturing

by Kelly Stewart

Executive Summary

In this white paper, we’ll explore the adoption of digital manufacturing execution systems (MES) for clinical drug development. 

We’ll begin by reviewing the usage of MES in pharmaceutical manufacturing. We’ll then walk through the entire drug production lifecycle, from preclinical to commercial. 

Next, we’ll zero in on what happens at the clinical stage. In conclusion, we’ll consider MES capabilities in the context of clinical needs and priorities.

Jump to…

What Is a Manufacturing Execution System?

Before diving into clinical manufacturing, let’s start with an overview of manufacturing execution systems: what they do and how they do it.

What does a manufacturing execution system do?

Manufacturing execution systems (MES) are computerized systems used by manufacturers to review and record the transformation of raw materials to finished goods.

Why do we need manufacturing execution systems?

MES provides information that helps manufacturing decision makers fine-tune their process to adhere to the steps that ensure quality as well as optimization and production output.

How does a manufacturing execution system work?

MES works in real time to facilitate control of multiple elements of the production process, such as inputs, personnel, machines, and support services.

What is manufacturing execution system software?

MES software connects and controls manufacturing processes with enterprise systems such as ERP and PLM. As Gartner explains in their 2021 Magic Quadrant, MES software also gives “feedback on process performance, and support component and material-level traceability, genealogy and integration with process history, where required.”

What is the difference between an MES and an EBR?

Manufacturing execution systems (MES) are systems that connect and digitize various parts of manufacturing, whereas electronic batch records (EBR) are the output of digitizing paper batch records. In other words, MES help to streamline digital manufacturing operations in a number of ways, one of which is by turning paper batch records into EBRs.

Drug Production Lifecycle: An Overview

There are three sequential stages to the drug production lifecycle: preclinical, clinical, and commercial. Manufacturers have varying needs and challenges to work through at each stage.

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What happens at the preclinical stage?

  • Goal: Taking a newly discovered molecule and figuring out the process to turn it into a safe medicine
  • Challenges: Needing to constantly experiment with processes to determine which ones work best
  • Resources: Limited IT involvement and technical resources

What happens at the clinical stage?

  • Goal: Taking the process determined in the preclinical stage and figuring out how to make it repeatable at scale
  • Challenges: Making enough drug products that are safe enough for clinical trials on animals and humans; deployment to operating suites limited to a few select locations
  • Resources: Limited IT involvement and technical resources

What happens at the commercial stage?

  • Goal: Making a high-yield, high-quality batch as frequently and quickly as possible
  • Challenges: Keeping overhead low at scale; connecting operating suites and collaborators across geographies and facilities
  • Resources: Significant IT involvement in matters such as budget spend, consolidation, and sourcing approved vendors

What Happens at the Clinical Stage?

At the clinical stage of pharmaceutical manufacturing, processes are still evolving to achieve quality by design. The core goal is to determine which factors can reliably create a quality batch at scale.

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What is clinical research?

After preclinical researchers establish the process, clinical manufacturers optimize the process to ensure that it’s robust and repeatable. To do this, they need to track and analyze massive amounts of data at every step.

Clinical research is conducted in a series of stepwise trials, with each phase having a set purpose and process:

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Source: FADIC

What do clinical scientists do?

Clinical scientists hone their manufacturing process by keeping track of critical process parameters, or CPPs. They safeguard drug quality at scale by ensuring critical quality attributes, or CQAs, are met.

As Apprentice Application Specialist Laura Jacoby explains, “It’s all about reproducibility.” There needs to be confidence in the process, which is gained by showing the desired outcome is reproducible.

“The top priority of clinical manufacturing is to create a process that’s going to have high purity and high yield with lower costs.”
—Laura Jacoby, Application Specialist at Apprentice

What do clinical scientists need to know?

Think of clinical process scientists as pharmaceutical detectives. If there is an unexpected outcome, they need to find out why and how it happened. Robust data is the key that makes it possible.

Only by tracking every type of change to process and resulting yield, can clinical scientists have the information they need to determine the ideal process. To do their best work, they need to track everything in the process that’s happening that may or may not be significant.

Clinical scientists need to determine:

  • Which process parameters affect drug purity and yield? 
  • If a single material or piece of equipment gets changed, how does that affect the batch?
  • Is the product still pure? Is the process reproducible? 
  • Did an element get introduced that needs to be isolated to maintain drug purity? 

These are only a few of the many questions that need to be answered at the clinical stage.

Clinical Manufacturing: What’s at Stake

Managing operations in pharmaceutical and cell & gene therapy (CGT) companies presents a number of challenges over and above those encountered by other manufacturing industries.

Why is clinical manufacturing challenging?

The key global markets for pharmaceuticals and medical supplies are heavily regulated by a variety of agencies concerned with ensuring public health is not placed unnecessarily at risk. 

This means manufacturers need to be able to demonstrate a high level of consistency and predictability in terms of the quality of the products they produce.

"Vaccine manufacturing is an endeavor where an almost infinite combination of things has to work perfectly."
—Prashant Yadav, Center for Global Development, Senior Fellow

They also need to be considerably more accurate in terms of traceability and device/batch record processing than other manufacturers who are not subjected to the same rigorous regulatory environment.

How often do clinical trials fail?

Another challenge to clinical manufacturing is the steep failure rate. Over 87% of clinical compounds fail to move on to commercial manufacturing, according to a recent analysis of 1,442 experimental drugs in clinical tests. 

“Approximately seven out of eight compounds that enter the clinical testing pipeline will fail in development. Put another way, you need to put an average of 8.5 compounds in clinical development to get one approval.”
—Joseph A. DiMasi, Tufts CSDD, Director of Economic Analysis

While the cost to develop new drugs keeps rising, the rate of clinical testing success grows smaller and smaller. 

Throw COVID into the mix, and you’ve got a perfect storm of clinical manufacturing hurdles to overcome.

Clinical Manufacturing in the Time of COVID

COVID-19 had sweeping impacts on the world at large, and pharmaceutical manufacturing was no exception. Overnight, there arose an instant, unforeseen demand for a new type of manufacturing. 

Scientists had to find a way to develop, research, and manufacture medicines without the luxuries of guaranteed onsite access and connected teams. 

As Apprentice CEO Angelo Stracquatanio explains, “All of a sudden this industry was forced to learn, adopt, and then deploy at an unprecedented rate to help solve these challenges that came up.”

“The COVID-19 pandemic has caused significant disruption to the research, manufacturing, clinical development, and market launch of CGTs for non-COVID-19-related diseases.”
—Tingting Qiu, Creativ-Ceutical, Health Policy Analyst

Supply shortages, trial recruitment, and regulatory delays are only a handful of the COVID-related challenges faced by clinical researchers. To meet these challenges, manufacturers had to find new ways of working. Enter digital MES.

COVID-19 sparked a huge uptick in the adoption of MES from clinical scientists. But why? How did paper systems fall short of adapting to the new normal of post-COVID clinical manufacturing?

The Problem With Paper

Now more than ever, speed, safety, and flexibility are crucial to bring new drugs to market.

Paper has long reigned supreme as a tried and tested method of capturing data. However, it comes with several major drawbacks in a clinical setting:

  1. Effort. Manually recording data on paper is laborious and time-consuming to maintain. Transcribing data from paper to a digital system adds even more time and effort.
  2. Vulnerability. Unlike digital MES, paper is susceptible to damage from water, smudges, and illegible handwriting. It’s also vulnerable to incomplete or missing information not getting captured.
  3. Lack of real-time data. Paper keeps Quality teams out of the loop and unable to address exceptions in the moment. Without the real-time visibility afforded by cloud systems, supervisors are left in the dark at crucial junctures and often need to follow a lengthy trail months later to determine the cause of a deviation.

Paper-based systems can also lead to inefficiencies such as slower execution, lower yield per batch, increased downtime, and more deviations.

“Pre-pandemic, the industry knew paper batch records were not the way to manufacture these incredibly complex drugs, but there wasn’t the incentive to deploy new technologies.”
—Angelo Stracquatanio, Apprentice CEO

In a post-pandemic world, paper just can’t keep up with the growing demands for speed and productivity in clinical manufacturing. 

So where is the future of clinical manufacturing headed?

Traditionally, paper systems have been used to track write-in parameters in batch records. Now, with the advent of electronic batch records (EBRs), more sophisticated options are available.

Why You Need a Digital MES for Clinical

Sure, paper works. But at what cost? Savvy manufacturing companies are stepping away from the paper and reaping the benefits of cloud-based MES.

“Economically, the cost of centralized, manual processes will keep therapies out of reach for patients and payers. This centralized approach also doesn’t work from a clinical perspective because of complicated logistics, time lags, and failed batches.”
—Labiotech.eu

Digital MES at the clinical manufacturing stage can help you achieve:

  1. Purity. Automated data capture gives you the information you need to optimize your batches for purity.
  2. Speed to market. Lengthy paper trails slow you down. Instantaneous cloud syncing can keep you on track.
  3. Capital. Say goodbye to losing valuable ROI on wasted batches due to exceptions that can’t be noticed and resolved in the moment.
  4. Distributed workforce. Virtual collaboration tools connect teams and sites all over the world with just the click of a button.
  5. Robustness. Capture massive amounts of data with ease. You’ll no longer be bound to the time and resource constraints of manual data capture and transcription.
  6. Parameters. Set custom programmable guardrails to prevent operators from completing a step when values deviate from defined ranges.
  7. Electronic batch records. Digital MES allows organizations to streamline batch processes and manage batch runs from a high level, which contributes to higher reliability and uniformity.
  8. Quality. Ensure all critical quality attributes are achieved and maintained.
  9. Process. Easily track all key variables in the production process to establish critical process parameters.
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Source: ARC Advisory Group

More and more, life scientists are moving away from the burden of paper to reap the benefits of twenty-first century digital solutions.

MES at the Clinical Stage: See It in Action

Sure, digital MES sounds good on paper. But what does it look like in action?

Let’s take a look at Bristol Myers Squibb, and how they’ve leveraged Apprentice digital MES technology to produce clinical trial batches with unprecedented speed and quality.

Meet Lucy Hawarden, a Bristol Myers Squib Senior Research Investigator and digital MES enthusiast:

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BMS Senior Research Investigator Lucy Hawarde using Apprentice Tempo MES

In the height of COVID, Lucy found a new way to monitor a pharmaceutical manufacturing facility in Asia. With Tempo digital MES technology, Lucy was able to monitor lab events at ease in real time from the comfort of her home office.

“I was able to remotely view all stages of the clinical manufacture, covering dispensing and blending, granulation, compression, and coating, and also give feedback to the team there.”
—Lucy Hawarden, Bristol Myers Squibb, Apprentice client

Lucy cites the time-saving power of digital MES as a big factor in keeping production on schedule. In her words, MES ensured that “the batches were successfully manufactured and released, keeping timelines for the drug’s development on track.”

MEET LUCY

Closing Thoughts: Tempo MES for Clinical

Apprentice's Manufacturing Execution System (MES) is the life science industry's only intelligent software platform built to support critical manufacturing processes and help organizations scale faster — from COVID to cancer. 

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Bristol Myers Squib Principal Scientist Nobel Vale using an Apprentice AR headset in the lab

What’s Tempo MES?

Apprentice’s end-to-end solution unlocks the power behind an organization’s data to improve reliability and increase speed to market. 

Our suite of intelligent solutions includes intelligent batch execution, augmented procedures, predictive resource management, smart equipment logging/tracking and AR-driven global collaboration.

Not just paper on glass

Our digital MES solution is so much more than just paper on glass. With intelligent batch execution and electronic batch records, Tempo MES empowers you to pull out data in real time that’s critical to analyze in the moment. 

Harness the power of the cloud

There’s no doubt about it: on-prem MES solutions can get really messy, really fast. Luckily, we’re proud to be a cloud-first company here at Apprentice. Our powerful cloud-based platform can reduce the effort and IT burden that you might expect with a traditional MES.

No coders? No problem 

MES is hard enough as it is. That’s why we took coding out of the equation. With Tempo MES, you can let your clinical scientists author and edit their own no-code recipes and procedures.

Decreased CapEx

Our cloud platform eliminates the need for costly hardware, updates, and customizations.

Learn more about how Apprentice's MES increases speed to market, improves yield per batch, and reduces deviations in clinical manufacturing.

EXPLORE CLINICAL

Meet Our Clinical Problem Solvers

From preclinical benchtop to commercial manufacturing, Tempo keeps your global teams connected, empowered, and in sync. Our cloud-based platform gives you the speed and flexibility you need at the clinical stage.

Got questions about our MES clinical solutions? Talk to our team of experts!

SAY HELLO

References

  1. Bristol Myers Squibb. (2021, March 18). Ensuring Drug Production During Pandemic with Augmented Reality – Bristol Myers Squibb. BMS. https://www.bms.com/life-and-science/science/augmented-reality-helping-in-drug-production-during-pandemic.html
  2. Center for Drug Evaluation and Research. (2018, August 24). PAT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance. U.S. Food and Drug Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pat-framework-innovative-pharmaceutical-development-manufacturing-and-quality-assurance
  3. Distributed Manufacturing of Cell Therapies Poses a Threat to Big Pharma. (2021, December 21). Labiotech.Eu. https://www.labiotech.eu/opinion/distributed-manufacturing-cell-therapy/
  4. Gartner. (2021, March 30). Magic Quadrant for Manufacturing Execution Systems. https://www.gartner.com/en/documents/4000002
  5. Gorbach, G. (2018, December 21). Strategies for Transforming Production Operations With 21st Century Software. ARC Advisory Group. https://www.arcweb.com/blog/strategies-transforming-production-operations-21st-century-software
  6. Nature Editorial, & Thanh Le, T. (2020, October 4). Evolution of the COVID-19 vaccine development landscape. Nature. https://www.nature.com/articles/d41573-020-00151-8
  7. Qiu, T., Wang, Y., Liang, S., Han, R., & Toumi, M. (2021). The impact of COVID-19 on the cell and gene therapies industry: Disruptions, opportunities, and future prospects. Drug Discovery Today, 26(10), 2269–2281. https://doi.org/10.1016/j.drudis.2021.04.020
  8. Sullivan, T. (2019, March 21). A Tough Road: Cost to Develop One New Drug Is $2.6 Billion; Approval Rate for Drugs Entering Clinical Development is Less Than 12%. Policy & Medicine. https://www.policymed.com/2014/12/a-tough-road-cost-to-develop-one-new-drug-is-26-billion-approval-rate-for-drugs-entering-clinical-de.html

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