Your Guide to Modernizing Commercial Drug Manufacturing

Executive Summary

Welcome to Part 3 of our preclinical, clinical, and commercial manufacturing series.

In Part 1, we explored the entire drug production lifecycle, and then examined what happens at the preclinical stage.

In Part 2, we analyzed clinical drug production and how digital manufacturing execution systems are used from preclinical to commercial stages.

Now, we’ll take a deep dive into commercial production by examining what’s at stake and what needs to happen for a drug to go to market. In conclusion, we’ll outline how pharma companies can modernize and optimize commercial drug production throughout the entire lifecycle.

Jump to:

Drug Production Lifecycle: An Overview

The drug production lifecycle encompasses three distinct stages: preclinical, clinical, and commercial. Naturally, as drugs move from one stage to the next the needs, obstacles, and goals at each point will evolve.

However, one thing pulls through for all three stages: the value of digital solutions for streamlining and optimizing communications and transfer of data, knowledge, and tech.

In this section, we’ll outline the purpose of these three stages, as well as the unique set of challenges and needs faced by drug manufacturers at each stage.

What is preclinical development?

In the preclinical development stage of drug production, researchers aim to determine safe doses and processes for treatments, drugs, or pharmaceutical procedures.

It’s a four-part process that includes drug discovery and development as well as assessing the drug pharmacology, also known as ADME (absorption, distribution, metabolism, and excretion), and toxicology. In other words, how the drug works and whether it’s safe.

Lack of efficacy is the main obstacle researchers aim to overcome during this stage of development. Failure rates are steep, with only ~33% of preclinical drugs moving on to the clinical stage. As such, having efficient testing processes in place that allow researchers to quickly determine if a drug is safe and effective is critical.

What is clinical manufacturing?

During clinical manufacturing, scientists and engineers focus on scalability. They analyze how to take the insights gathered during the preclinical stage and make the results repeatable at scale. The ultimate goal of this stage is to determine whether proposed products are safe and effective. 

This stage usually takes years to complete and involves four clinical trial phases. Each phase is designed to test and analyze the safety and efficacy of drugs on human subjects. Not all drugs will make it through each phase, as those that are proven to be unsafe or ineffective are weeded out.

Due to the nature of this stage, failure rates are high — hovering around 90%. To reduce costs and save time, the biggest challenge researchers face is getting to the golden batch faster, and making sure production of that batch is scalable.

What is commercial manufacturing?

When a drug is ready for commercial manufacturing, medicinal products are developed and launched at scale. To be successful, the recipe needs to be “hardened” — meaning it’s perfected, solidified, and then followed to a tee. Any deviations in this process will result in delays, additional costs, and quality issues. 

For every single batch, the entire process must be recorded and controlled to fully support compliance throughout every step of production. The ultimate goal is to make high-yield, high-quality batches as frequently and quickly as possible.

Commercial Stage: What’s at Stake

What happens during commercial manufacturing?

Commercial manufacturing kicks off with a full FDA review. After the FDA approves a drug, manufacturing can begin. This involves turning raw materials into finished products, and includes specialized teams, equipment, materials, facilities, and various stages. 

During this process, the drug substance, aka the pure material of the drug, is turned into the drug product, the final finished form of the drug including its added ingredients and packaging.

Initially, a pharma company will set its commercial team up with the necessary data to begin manufacturing, such as the clinical trial reports and golden batch record. The next step is to create the first batch, which will be tested for quality, purity, and efficacy.

Drugs go through rigorous testing throughout the production process to ensure they are safe, cGMP compliant, and effective prior to commercialization.

To successfully manufacture drugs at scale, many pharma companies rely on technology powered by digital technologies, including manufacturing execution systems (MES) and laboratory execution systems (LES). Advanced, cloud-based technologies like MES and LES solutions streamline drug production, allowing manufacturers to maintain quality control and compliance while working faster and more efficiently.

Why is commercial manufacturing important?

Commercial manufacturing is important because it is the final crucial step after therapies are approved by regulatory bodies for mass production. It enables patients to receive drugs capable of preventing, treating, or curing various diseases and conditions. 

In doing so, it helps to improve the quality of life for people around the world, by delivering them drugs that will help them live a longer, better, healthier existence.

Commercial manufacturing in the time of COVID 

The typical timeline for vaccine development is 10 to 15 years. This process involves a slew of animal and human trials, as well as testing for safety and efficacy. However, in the midst of a global pandemic the world didn’t have a decade to spare, so the Food and Drug Administration (FDA) launched the Coronavirus Treatment Acceleration Program (CTAP). 

The CTAP’s mission is to “use every available method to move new treatments to patients as quickly as possible, while at the same time finding out whether they are helpful or harmful.” 

By leveraging cutting-edge technologies such as artificial intelligence (AI) and machine learning (ML), coupled with traditional drug discovery tools, life science companies have been able to accelerate the screening process and begin testing potential drugs sooner.

Here are some of the key highlights: 

• March 2020: Moderna starts phase 1 vaccine trials
• April 2020: BenevolentAI, an AI and ML company, identifies baricitinib as a treatment for severe COVID; it reduces mortality by 38%
• December 2020: Emergency use authorization (EUA) is granted for Pfizer-BioNTech and Moderna COVID vaccines
• February 2021: The J&J vaccine is approved for EUA
• August 2021: The FDA issues full approval for the Pfizer-BioNTech vaccine 
• 2020 – present: COVID continues to expedite tech adoption among drug developers and manufacturers, helping to usher in the era of Pharma 4.0

How were COVID vaccine manufacturers able to accelerate commercial rollout so drastically? By tapping into the power of digital technology.

We’re proud to say that our Tempo MES technology has helped to rapidly convert manufacturing facilities and production lines to produce an estimated 370 million mRNA vaccine doses.

Ultimately, COVID has illustrated that top tech coupled with government support enables pharma companies to accelerate every stage of drug development.

Commercial Manufacturing: Challenges and Solutions

Why is commercial manufacturing difficult?

Commercial drug manufacturing involves a lot of moving parts that need to be considered including supply chain disruptions, inventory management, collaboration across teams and sites, and beyond. As such, to be successful in bringing new therapeutics to market, companies must approach manufacturing with agility and flexibility. 

However, this is often easier said than done. Many pharma companies still rely on outdated processes such as paper records and on-premise legacy systems for manufacturing. Although these systems are tried and tested, they weren’t built for modern manufacturing and create bottlenecks in the production process.

Here are some frequent challenges commercial drug manufacturers face:

• Supply chain disruptions: From inventory management to ingredient availability and changing consumer demand, supply chains are always in a constant state of flux. Organizations unable to adapt quickly end up inadvertently wasting time, money, and other resources.
• Changing regulatory compliance requirements: As drug manufacturing changes — thanks in large part to innovative technologies — so do the regulatory requirements. As such, companies must always be ready to adhere to new guidelines at the drop of a hat. Naturally, this represents a real challenge for any organizations that rely on legacy systems or paper processes, as they weren’t built for change.
• Inefficient collaboration: Cross team and site collaboration is a crucial component of commercial drug production. When teams work together by leveraging real-time data, errors are reduced and efficiencies increase. In contrast, when the data is inaccurate, incomplete, or outdated, issues arise that can lead to quality control problems, production delays, and beyond.

The problem with on-prem systems

In order for pharma companies to replicate the COVID vaccine production model, they need to have a consistent digital solution across manufacturing operations. This means data is accurate, visible, and available in real time across sites and teams.

The problem with on-prem legacy solutions is that they’re siloed across individual sites, meaning the information contained within them is only available to certain people, in certain locations. As such, collaboration is stifled and teams may be working from inaccurate or incomplete data. This leads to redundancies like the duplication of work, wasted resources, and processes deviations.

By leveraging cloud-based systems, companies can work as one team from anywhere while seamlessly managing workflows and processes across sites.

“While many commercial manufacturing teams leverage digital solutions today, there are limitations with existing on-premise technology. A main limitation is lack of connectivity to other sites and teams, which makes initial scale-up and technology transfer challenging.”
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— Anastasia Wengrowski, VP, Strategy, Apprentice

What this means for go-to-market

Modernizing commercial drug production allows companies to bring new drugs to market sooner. It also reduces the risks associated with each stage of development, and helps companies adhere more stringently to quality standards and regulatory requirements.

The importance of this cannot be overstated. Given the competitive nature of drug development, volatility of the market, and high failure rates, pharma companies need all the help they can get to reduce the risks, while increasing their chances of success. Companies that opt to stick with manual processes or outdated solutions will eventually be left behind, unable to compete with the quick pace of the market.

The Future of Commercial Manufacturing

Why you need a cloud-based MES solution

Although many pharma companies are equipped with MES solutions for commercial manufacturing, many of these solutions are outdated and on-prem. As a result, information can’t be shared in real time, which hinders collaboration and may result in resource waste.

Companies that choose a cloud-based solution remain more competitive in the market because they’re able to bring products to market sooner, without sacrificing quality or safety along the way.

Here are five reasons you need a cloud-based MES solution:

1. It enables seamless tech transfers.
2. Teams can communicate from anywhere, anytime.
3. Multiple teams can operate from the same system, and even the same recipe.
4. It offers automated data capture for electronic batch records, which ensures compliance.
5. Exceptions can be reviewed in real time, which allows companies to remedy issues on the spot.

And if you need another reason beyond those listed above, consider this statistic:

How to modernize your commercial manufacturing operations

Here’s our advice: Select a suitable MES solution from the start. This will enable you to avoid unnecessary issues down the road, and ensure your organization is set up for success from day one. If this isn’t an option because you already have an MES system in place, then take the following steps to modernize your commercial manufacturing operations:

1. Assess current weaknesses. Analyze your organization’s existing structure and outline where production weaknesses exist. For example, are there gaps in how you communicate with your suppliers, resulting in longer lead times? By isolating organizational weaknesses, you can make informed decisions about what systems need to be modernized in your manufacturing process, and which are already meeting your organizational needs.
2. Incorporate digital systems. One of the easiest ways to get started is to look for ways you can replace paper records with digital solutions, such as electronic batch records. This will enable your organization to capture, transcribe, and centralize data in real time, which reduces human error, and ensures everyone involved in the production process is working from the same information.
3. Use a combined MES/LES. Data makes the pharma manufacturing world go round. By using a combined MES and LES solution, your organization can eliminate siloed data and process transfers. This keeps batches moving faster by executing a seamless workflow across steps and teams that are typically siloed in separate execution systems. 
4. Leverage virtual collaboration. AI-powered headsets and other devices allow your employees to connect with each other in real time from anywhere. As such, these devices enhance the collaboration process and enable teams to avoid the duplication of efforts.

We know that’s a lot to swallow. But before the fire alarms sound off, note that there’s no need to make a wholesale pivot from paper to digital, or from on-prem to the cloud.

Change management works best when it’s approached thoughtfully, so consider incremental changes that can start moving you towards your goals. Create a tiger team of digital champions who can start working with a new technology, pilot it, and then make recommendations on how to grow it out from there.

As with any big change, modernizing your drug production process will take time.

Have patience as you work to make changes, make sure communications are coordinated across the entire organization, and do your research. Don’t just go with any system that claims to offer the benefits listed above, make sure the solution you select can also deliver on its promise.

Closing Thoughts: To Optimize, Modernize

Perfecting a therapeutic product and bringing it to market is no easy feat. It takes an average of 12 years, trial and error, and millions (sometimes billions) of dollars.

So, what’s at stake during the commercial stage? Everything. Time. Money. Resources. Your company’s reputation. And most importantly, your product.

To accelerate commercial production, pharma companies need to connect operating suites and collaborators across geographies and facilities. As such, they must ensure whatever digital solutions they’re using are capable of detailed record keeping that allows for seamless transfers across sites, teams, and organizations.

“Modern digital solutions are becoming increasingly important in the pharmaceutical space because they can drastically reduce speed to market for life-saving treatments, getting medicines to patients faster.”

— Anastasia Wengrowski, VP, Strategy, Apprentice

Having a system that’s easy to use, and provides stakeholders with clear visibility throughout production can mean the difference between success and failure.

Improve your company’s go to market strategy — from preclinical benchtop to large-scale commercial manufacturing, by leveraging our Tempo Manufacturing Execution System (MES). Tempo keeps your global teams connected, empowered, and in sync. It’s flexible, yet powerful, features let Tempo grow with your process from preclinical experimentation to commercial standardization.

Want to learn more about how you can scale faster and smarter with Tempo MES? Get in touch with our team and we’ll show you how.

Our Featured Thought Leader

Anastasia’s passionate about science, technology, and how they intersect. Read on to learn more about her background and insights on commercial manufacturing.

Meet Anastasia, Our Commercial-Stage Champion

• Who: Anastasia Wengrowski, PhD
• What: VP, Strategy
• When: < 1 year at Apprentice
• Where: Huntsville, AL
• Why: With both a medical and a consultative background, Anastasia’s able to see both sides of the picture and stitch them together in her go-to-market strategy

Anastasia’s Background

Anastasia has joined the team at Apprentice and is excited to be helping the life sciences industry improve reliability and speed to market with the Tempo platform!

Anastasia is a Certified Quality Auditor with diverse experience in life sciences academic research, regulatory affairs, quality systems, and cloud technology. She began her career conducting cardiac physiology research in a biomedical engineering laboratory, where she led projects, taught courses, and published full manuscripts. This passion for cardiac physiology led to a position as a medical device and combination product reviewer for the FDA.

At the FDA, Anastasia worked with a cross-functional team of experts across multiple centers (CDRH, CDER, and CBER) to provide premarket approval for implantable electrophysiology devices such as pacemakers and drug-coated leads. Anastasia then spent several years working in the life sciences industry, where she learned all aspects of the quality system and also implemented an electronic quality management system.

From 2018 to 2021, Anastasia worked at Veeva Systems. She spent time as an implementation consultant before moving over to the Vault Quality strategy team, where she was responsible for growing and supporting Veeva's customer base in the life sciences market.

In her current role of VP of Strategy at Apprentice, Anastasia helps pinpoint and resolve common challenges faced by manufacturers across the drug production lifecycle — from preclinical through clinical to commercial manufacturing.

MEET ANASTASIA

Commercial Manufacturing: Anastasia’s Point of View

“It’s a common misconception that digital solutions are necessary only for commercial stage drug manufacturing, in order to optimize production and maintain compliance.

In reality, implementing a flexible, modern solution earlier on in the development and manufacturing process (as early as the preclinical stage) can accelerate the drug development lifecycle by removing barriers, providing access to data, and facilitating tech transfer.”

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