In Part 1 of this series, we defined tech transfer and then examined it from multiple angles: from chocolate chip cookies to pharmaceutical manufacturing.
Now, we’re ready to zero in on an especially crucial tech transfer point in pharma: the jump from preclinical to clinical.
First, we’ll explore what needs to happen during this switch from preclinical drug development to clinical manufacturing. We’ll then walk through some of the top obstacles scientists encounter at this junction.
In conclusion, we’ll explore several ways to address these challenges through modern technology solutions.
- I. What Is Preclinical to Clinical Tech Transfer?
- II. Why Is Preclinical to Clinical Tech Transfer So Important?
- III. Why Is Preclinical to Clinical Tech Transfer So Challenging?
- IV. How Can I Optimize My Preclinical to Clinical Tech Transfer?
- V. Tempo for a Complete Tech Transfer
- VI. References
I. What Is Preclinical to Clinical Tech Transfer?
When a drug moves from preclinical development to clinical manufacturing, it’s a matter of scale.
All the procedures created by process development teams must be shared and then optimized by manufacturing teams. At this early stage, the data tends to consist of information about the drug products, such as chemical properties, characterization, information and procedures, stability data, and safety data.
Clinical manufacturers need to figure out how to take all this data, and then use it to maximize yield without compromising the purity or safety of the drug. They achieve this either by replicating existing processes at scale, or by figuring out a new way to get the same results but with a much higher yield.
To get this right, several things need to happen. The preclinical sending team needs to:
- Gather all needed data
- Organize their data
- Transition their data
Then, the receiving team at the clinical site needs to:
- Retest every step
- Document all their retesting
- Compare this new output to preclinical results
- Rinse and repeat until they can achieve the same results
II. Why Is Preclinical to Clinical Tech Transfer So Important?
Between the preclinical and clinical stages of drug development, so much is still up in the air.
Processes haven’t yet been optimized, which means that there’s a higher need for detailed data. Nothing’s set in stone, which means that any set of data could be valuable to the final clinical procedures.
Without an established process, there’s no telling what could prove useful as the drug progresses along its journey. Better to be safe than sorry, which means being detailed versus deficient in your documentation.
The problem is that a massive amount of data is needed to encompass all the different procedures, equipment setups, protocols and reports, methods, output, validation, parameters, and equipment guidelines.
“The safety, quality, and efficacy requirements of lifesaving but potentially toxic pharmaceuticals put high demands on production. Producing complex drugs is not just a matter of building the required production line or hardware. It also involves a complex (and often finicky) manufacturing process, a large team of experts, a lot of time, many detailed steps, and the right regulatory registrations — and all of this against the highest quality standards.”
— Cormac O’Sullivan, Associate Partner, McKinsey
Safety is another top reason why the jump from preclinical to clinical is so important. Preclinical processes get tested on mice, but clinical trials are conducted on people. When human lives are on the table, the stakes get significantly higher.
These safety requirements, along with the sheer amount of data needed to meet them, means that tech transfer at this stage is both hugely valuable… and also very difficult to achieve.
III. Why Is Preclinical to Clinical Tech Transfer So Challenging?
So, what makes the tech transfer from preclinical to clinical so difficult to get right? It boils down to five main obstacles:
Challenge #1: Uncertainty.
At this early stage, there’s uncertainty about a number of factors, such as the:
- Scalability of the process; whether it can be replicated at scale
- Needed materials, which may or may not comply with GMP
- Equipment between sites, which is likely to differ
- Capacity requirements and dose requirements
“Sizing a facility is difficult because capacity requirements for preclinical, clinical, and commercial manufacturing can vary by several orders of magnitude because of uncertainty in process yields, dose requirements, and patient populations. Additional uncertainty can also come from the number and nature of the unit operations required to make the product.”
— Mark F. Witcher, PhD, SVP of Manufacturing Operations, Covance Biotechnology
To further complicate matters, new variables will be introduced by nature of the process moving from one site to another.
Challenge #2: Resource drain.
Manufacturing and testing drugs are complex processes requiring frequent adjustments, especially during preclinical and clinical development stages. At this junction, there’s a massive amount of documents and records and knowledge that needs to be captured, organized, and transitioned.
But that’s just the start: the receiving team needs to be able to understand and retest all of it. This requires a major investment of time and resources from both sides.
Challenge #3: Format.
There’s no guarantee for the documentation methods between the two stages to be the same. If the new environment is a different format, this can complicate the data mapping and may lead to lost or incorrectly transferred data.
Challenge #4: Legacy systems.
Tech transfers are vital to progressing operations, but they can be error-prone when based on paper and tribal knowledge. Paper documentation may be incomplete or unavailable, and verbal information can be miscommunicated or misunderstood.
When multiple disparate point solutions are used by an organization, there is an increasing number of tech transfers that are needed, as well as complexity to match.
And the amount of paperwork needed on paper systems… is daunting to even consider, much less to parse through.
Challenge #5: The COVID factor.
Pharmaceutical tech transfer in a post-COVID world boils down to two main complications:
- Speed to market, which has become even more critical. The challenges have gone up, but the timing expectations haven’t relaxed, meaning that operations need to be as efficient as possible.
- Remote workforce, which has become the new normal. Teams are now distributed across sites and even continents, with people needing to review and approve documents from afar.
At the jump from preclinical to clinical when so much is still up in the air, both of these complications get amplified. With so much data to parse and transfer, time is of the essence and communication is crucial. Navigating these demands puts a strain on both.
IV. How Can I Optimize My Preclinical to Clinical Tech Transfer?
Optimizing your preclinical to clinical tech transfer is all about making it as detailed, yet seamless, as possible. To achieve this, we recommend the following six best practices.
- Communicate proactively so that potential misunderstandings can be addressed early on.
“Successful technology transfer depends on reliable communication, planning, and documentation executed by results-oriented team players, which involves assembling appropriate members from both sites (sponsor and CDMO), ideally with each member having a counterpart to ensure direct transfer of knowledge and good communication.”
— Barrett Fallentine, Director of Product and Process Development, Pharmatech Associates
- Be aware of what's changed so all adjustments to your process can be accounted for.
“Although a transferred process should ideally remain the same as the original, in practice the process always undergoes some adaptation at the receiving site, mostly due to the difference in equipment between the sending and receiving sites as well as the need for scale-up of the entire process.”
— Tangir Ahamed, PhD, Senior Scientist, VBI Vaccines
- Start thinking at scale to meet clinical output demands.
“Scale-up is common, especially in early clinical phases. At first glance, it might not be considered a change because most of the associated processes can be described in scale-independent ways. Yet practice and theory show that many factors can change during scale-up.”
— Thomas Chattaway, Senior Life Science Consultant
- Keep an eye on your equipment and be mindful of the impact of slight changes.
“During technology transfer there can be many reasons for changing the processing equipment used — perhaps better or more efficient systems are available such as for washing or isolating cells, or to take advantage of improvements in monitoring and control, or simply because scaling-up laboratory systems such as culture plates is not feasible. Even slight changes to equipment can change the processing environment.”
—Trefor Jones, Technology Transfer Specialist, Bluehatch Consultancy
- Document, document, document all your procedures and knowledge at every step.
“Documentation is not an event, but a best practice to be implemented, and referred to, at every step along the way. Templated standard operating procedures and documents, approved by the quality team, will increase the speed, efficiency, effectiveness, and quality of technical transfer.”
—Joe Makowiecki, Enterprise Solutions Director of Business Development, Cytiva
- Digitize your operations and consider future-proofing them through cloud technology.
Digital documentation solutions give you an easy way to track and share all your tech transfer data. And when you go digital, you should go straight to the cloud so that you can future-proof your systems and get the flexibility to scale up and out.
Cloud technology ensures that all the data and documents you need can be instantly logged and shared between sites and teams. Better yet, the cloud makes it easy to not just gather, but navigate between the vast amount of data needed in early-stage drug development.
V. Tempo for a Complete Tech Transfer
At Apprentice, we think that manufacturing a drug and bringing it to market is hard enough as it is. That’s why we’re here to make your tech transfer process as seamless as possible.
Our Tempo Manufacturing Cloud removes the obstacle of information being in different places. Preclinical and clinical teams can both use our manufacturing execution system, making tech transfer between the two quick and effortless.
How do we achieve this? Through real-time cloud technology, embedded at every step along the way.
Our secure cloud platform makes it possible for resource definitions, master recipes, and production data to be shared instantly across teams, ensuring all members have access to the right information at the right time.
With our cloud-native approach, access to Tempo and the information needed for a tech transfer is available immediately, not restricted by deployment and geography.
“Tempo aims to streamline the source and destination matching. Our platform is so powerful because we’ll be able to take preclinical records and data, and facilitate their transfer to clinical teams in Tempo. Teams will be able to leverage what’s already there instead of having to recreate everything.”
— Anastasia Wengrowski, VP of Strategy, Apprentice
Through Tempo, resource information is available in real time, whether through manual updates or automatically through IoT integrations, giving teams up-to-date resource visibility. As a result, teams can make fast and informed decisions — from which location is ready for a production run, to which piece of equipment is delaying the next step.
Our Tempo platform is designed to work as well on the manufacturing floor as it can in the lab. Accommodating both MES and LES capabilities, it’s the complete package that can take you all the way from preclinical benchtop to large-scale commercial manufacturing. Discover Tempo for tech transfer.