Almac Sciences Accelerates Contract Manufacturing With Electronic Batch Records

How to Adhere to GMP Standards for Personalized Medicine With a Flexible Manufacturing Solution

Almac Sciences is trusted by leading global biopharma companies to provide crucial services across drug development projects. In the last five years alone, Almac Sciences has contributed to approximately 50% of all new molecular entities (NMEs) approved by the U.S. Food and Drug Administration (FDA) and is currently supporting 30% of gene therapy products approved/pre-registered by the European Union (EU).

Almac Sciences is well-known for providing the following services:

• Research and development (R&D).
• Diagnostic services.
• API manufacture.
• Formulation development.
• Clinical trial supply services.
• Commercial-scale manufacture and distribution.

One of the company’s areas of expertise is high throughput peptide manufacture for use in individualized cancer vaccines. To deliver this cutting-edge service, Almac Sciences set up a facility in Edinburgh, Scotland, designed specifically to meet the exacting demands of good manufacturing practice (GMP) that these products demand. They are poised to continue being a trusted leader in contract manufacturing as they push the frontiers of these newly developing therapeutics.

New Approaches to Complex Targets

Almac Sciences started as a CDMO focused on conventional pharmaceuticals, providing pre-commercial services to large pharmaceutical companies where it can take many years for molecules to go through clinical development. However, with the explosion of advanced therapeutics in clinical trials over the past decade, Almac Sciences saw an opportunity to serve a new segment of the market.

Over the last 10 to 15 years, interest in peptide molecules has increased due to their unique chemical properties. The peptide is a middle-sized molecule, falling somewhere between smaller conventional drug molecules and larger biologic proteins. They are effective at targeting particular disease types, which makes them ideal for use in personalized medicines and cancer vaccines. Conventional peptide therapeutics take many months to develop and manufacture. But for individualized therapies, the requirements are different. Multiple products need to be manufactured in days.

This new frontier in therapeutics has completely changed the manufacturing landscape over the last four to five years, according to Alastair Hay, VP of Peptides at Almac Sciences.

“I think the challenges are a mixture between technical and regulatory,” Hay said. “The landscape is changing a lot in terms of the types of diseases and the complexity that we’re trying to treat. Sponsors and inventors are creating ever more complex molecules and you need to overcome manufacturing challenges and develop new approaches to reach those more complex targets.”

Winning the Race for Personalized Medicines in Record Time

Unfortunately, as Almac Sciences was recognizing their opportunity to supply a new market for personalized medicines, traditional paper-based manufacturing processes were creating bottlenecks that impeded high throughput manufacture.

Historically, completing a production batch would have involved many hundreds of pages following the manufacturing process through to completion. Each activity needed to be manually recorded, dated, and signed by operators. The information required to move production along could be entered incorrectly, written illegibly, or even inadvertently go unrecorded. The steps involved were by necessity sequential. All of this translated to long production cycles, which personalized peptide production cannot tolerate

As complex as the targets were, the solution needed to be simple so they could hit the ground running.

“From a product point of view, we were looking for something that was easy to set up, easy to use, gave us a consistency in the quality, and had the functionality we (were) looking for,” according to Hay.

Almac Sciences chose MasterControl’s Manufacturing Excellence, a modern manufacturing execution system (MES) software solution. The solution’s digital production records that reduce human errors and shorten batch review times have made the most dramatic difference, according to Laura Glenn, production supervisor at Almac Sciences.

“It’s shortened the time I need to do batch book reviews, because they’re just there and I can do them at any time of the day,” Glenn said. “I don’t need to gather all the paperwork together and look through it all. I can have 10 tabs open at once and it’s way easier.”

This is very important because, for each production batch, Almac Sciences typically has a set of 80 different manufacturing directions (MDs).

Martin Ross, quality manager for Almac Sciences, is on board with these improved manufacturing processes.

“It’s not apparent until you adopt an electronic system that you’ve been constrained by those paper systems,” said Ross. “So just through the act of adopting the system, you see new ways of working, new opportunities that can improve compliance and effectiveness and save you time and resources.”

Working Closely with Regulatory Partners

Almac Sciences’ analytical testing laboratories are fully certified by appropriate authorities including Medicines & Healthcare Products Regulatory Agency (MHRA) and the U.S. Food and Drug Administration (FDA). Working at the edges of pharmaceutical development and making each product unique requires them to keep up a consistent dialogue with regulators. Almac Sciences needed a flexible solution that would allow them to adopt high-variability and low-volume production while maintaining their high-quality standards. They also had to keep in mind their high throughput requirements and make provisions for future scalability as they anticipate commercialization.

“The technical aspect is a continually evolving challenge,” said Hay. “When you’re pushing new frontiers, there isn’t necessarily regulatory precedent. That means that you have to invent things as you go and work closely with the regulatory partners to make sure that you’re keeping patient safety paramount in everything you’re doing.”

An Audit Success Story

Almac Sciences undergoes numerous audits annually from various entities including regulators and clients. From the regulator’s perspective, digitization has provided great advantages due to the company’s continuous state of readiness and easy access to necessary documentation. Their audits generally take a very short time to complete.

“When we’re audited both by clients and regulators, they love it because we can get MasterControl up on the screen in the audit room and just show (them) as soon as (they) ask,” Ross explained about their success with audits. “There’s not a lag in finding a record. It’s done there and then. Showing that level of control, goes a long way in an audit.”

Clients feel confident because they can see that specification and quality standards are being met.

Quality is a Competitive Advantage

Almac Sciences is not the only contract manufacturer in the industry, or even the only one targeting peptides. They differentiate themselves by strict adherence to GMP. With Manufacturing Excellence, manufacturing chemists and managers can launch quality forms directly from production records, allowing for in-line quality assurance and real-time quality control.

In their own words, product quality is driven by patient safety and Almac Sciences takes this seriously as their licence to operate. Customers may choose another manufacturer who is cheaper, but they will be sacrificing the quality of the products they end up with. It’s getting it right and getting it safe that matters.

Production supervisor Laura Glenn puts this focus on quality into perspective.

“There’s lots of other companies that make peptide products, but we make them to GMP standards,” Glenn said. “So when we deliver our products, we have a whole quality system behind (them). It’s keeping our standards high and also doing it quickly.”

In a critical manufacturing environment like the one in which the Almac Sciences team works, lives are on the line. That knowledge makes employees like manufacturing chemist Sarah Sinton more personally invested in their jobs.

“I think this work is important,” Sinton said. “It definitely impacts how we approach our day-to-day, knowing that if we work that little bit harder and strive to make it that little bit better or do it that little bit faster, then that could get to the patient quicker.”

A Flexible Manufacturing Solution for Personalized Products

Prior to using Manufacturing Excellence, Almac Sciences’ processes required quality personnel to prepopulate multiple iterations of necessary forms by hand. Now the quality managers preapprove directions using digitized templates that operators can then choose from. Previously, the company was also forced to rely on quality personnel to release all their batch records at the end of the production cycle. Production supervisors can now directly release the completed manufacturing directions. These cooperative improvements reduce the work burdens placed on quality personnel and free up the records that manufacturing personnel need to complete their work.

One of the key benefits of Manufacturing Excellence, according to Sinton, is that it allows multiple people to use the same batch record at the same time. That gives Almac Sciences a great advantage because employees often have laterstage processes detailed in the same manufacturing directions in which other employees may be working on an earlier process.

With MasterControl, Sinton said, “two people can do that same thing without having to switch the paper between each other.”

This new digital flexibility is another one of the benefits Almac Sciences has seen using MasterControl manufacturing software. It has inspired them to creatively optimize their own processes by flexibly assigning and completing essential manufacturing and quality tasks in a timely way, completing them simultaneously where possible, and even remotely via the cloud any time of day. Electronic records make manual transcription unnecessary and serve to error-proof their production records. All of this translates directly into faster batch release times and viable products

Foundations for Scalability and Future Commercial Growth

Pre-approval inspections are becoming more common for Almac Sciences as they embrace the feasibility of commercialization. A modern MES solution that has been able to support the cutting edge of medical science has allowed them to wonder if at some point in the future it would be possible for all treatments to be personalized.

“You’ve got scope to be able to create a new world, and that creates openmindedness,” Hay said. “You need to be able to think well out of the box, both from the technical and manufacturing point of view, but also a regulatory point of view to be sure that you can deliver what the market is pushing for.”

As for the immediate future, the facility’s manufacturing operations will be expanded to double their current size within the next three months. Almac Sciences is confident it can do so using MasterControl Manufacturing Excellence.