Creating New Know-how for the Encapsulation of mRNA-Based mostly Vaccines in Lipid Nanoparticles (LNPs)


The COVID-19 pandemic has necessitated the speedy growth of recent applied sciences for vaccine growth and supply. One key growth has stemmed from the necessity for largescale manufacturing of mRNA-based vaccines encapsulated in lipid nanoparticles (LNPs), enabling fragile mRNA-based vaccines to higher combine into sufferers’ cells.

KNAUER has been on the forefront of this very important growth within the battle in opposition to COVID-19, with the corporate’s Impingement Jets Mixing expertise offering a platform for the excessive circulation manufacturing of lipid nanoparticles.

We not too long ago spoke to Dr. Paul Pietsch from KNAUER in regards to the firm’s background, its vary of specialisms and its pioneering work to facilitate the largescale manufacturing of LNPs whereas assembly the stringent rules and exacting calls for of the biopharmaceutical business.

Please might you clarify what KNAUER can present to engineers and business professionals?

KNAUER has been producing high-quality scientific devices since 1962. We’re an skilled accomplice within the supply of apparatus to be used within the pharmaceutical business, comparable to liquid chromatography programs and expertise for lipid nanoparticle manufacturing and encapsulation.

We’re proud to have many consultants in our group, enabling us to develop modern and particular person options designed round every of our clients’ distinctive challenges. Along with this, we offer engineering companies to develop programs that meet the precise wants and necessities of our finish customers.

What can KNAUER supply the pharmaceutical business that its rivals, maybe, can not?

There are various firms on the market supplying gear and programs to the pharmaceutical business, they usually are available in many sizes and shapes; nonetheless, KNAUER nonetheless has a singular providing for our companions within the pharmaceutical business.

Firstly, we’re a longtime firm that has been working for nearly 60 years. All of those years of expertise imply that we’re properly versed in offering customized system options to our companions.

Secondly, we’re neither too massive nor too small. Our medium firm measurement implies that we will reply flexibly to the wants of our clients – like we did throughout the coronavirus pandemic with our lipid nanoparticle expertise – while nonetheless having the manpower to ship options at pace.

Our third distinctive power is that we produce all of our programs in-house at our headquarters in Berlin. Our on-site manufacturing permits us to rapidly adapt our current programs to our clients’ wants utilizing our personal CNC manufacturing, gear meeting line and software program growth group.

For instance, if a buyer wants a particular valve to finish a system that’s not obtainable available on the market, our development group can design the required half in keeping with their necessities.

Following design, the half can then be produced by our CNC manufacturing and hooked up to the system. Our software program group can then program any capabilities wanted to combine the valve. This whole course of can quickly be carried out in-house, relying on the time calls for of our clients.

To summarize all of this – KNAUER can present out-of-the-box, customized options for the pharmaceutical business as and when required.

An instance of a customized system designed by KNAUER – this technique makes use of 16 pumps for the purification of monoclonal antibodies.

mRNA vaccines have at present been making headlines – how do KNAUER assist in their manufacturing?

Essentially the most appropriate supply format for mRNA-based vaccines is lipid nanoparticles (LNPs). LNPs encapsulate the mRNA utilized in coronavirus vaccines and the ensuing lipid capsule protects the delicate mRNA from degradation, growing integration into the affected person’s cells.

The mRNA encapsulation course of makes use of Impingement Jets Mixing expertise, the place two streams (one containing lipids and one other containing an aqueous answer of mRNA) collide at excessive velocity in a jet mixing chamber – it’s this step that KNAUER’s expertise is concerned in.

With our experience in programs engineering and high-pressure dosing, we have been in a position to supply a serious pharmaceutical producer the expertise they required for the excessive circulation manufacturing of lipid nanoparticles.

Our Impingement Jets Mixing Skids have proven excellent efficiency within the large-scale manufacturing of mRNA encapsulated in lipid nanoparticles to be used in coronavirus vaccines. These at the moment are getting used globally in comparable purposes.

Schematic diagram exhibiting the blending course of occurring inside an IJM system.

Are there any breakthroughs or developments that KNAUER is pioneering that you’re significantly enthusiastic about?

The Impingement Jets Mixing (IJM) Skids we lined within the final query are what excites me most proper now.

Earlier than the coronavirus disaster, gear for the manufacturing of LNPs solely existed at a laboratory scale, which means the largescale manufacturing of mRNA encapsulated in LNPs was not but doable.

The coronavirus disaster meant that expertise that may very well be used within the giant scale manufacturing of mRNA-based vaccines all of a sudden grew to become urgently essential. This posed a problem as the massive scale manufacturing of such programs had not but been undertaken, and the lab-scale manufacturing of LNPs was not simply scalable.

To resolve this drawback, we mixed a number of lab-scale items in parallel to provide our IJM Skids, which might then be used for LNP manufacturing at a big scale. This feels like a easy answer, and, in principle, it’s. Nonetheless, it required a excessive diploma of finetuning and experience to implement this in keeping with the rules and calls for of the biopharmaceutical business.

Our current gadgets needed to be tailored for pharmaceutical manufacturing, which included the design of customized manifolds for inlets and retailers, circulation path optimization, design adaptation to fulfill clear room C necessities and the availability of interfaces for our clients’ personal PLC programs.

We’re proud to have performed a job in making historical past with coronavirus mRNA vaccines, being the primary instance of the usage of mRNA-based LNP vaccines. We’re much more proud to have finished all of this underneath unbelievable time strain, serving to to ship a coronavirus vaccine when the world wanted it most.

KNAUER’S IJM Skids have performed such an important position within the manufacturing of mRNA coronavirus vaccines in Germany that the German Chancellor herself visited the corporate in September 2021.

What sorts of initiatives within the pharmaceutical business has KNAUER been concerned in?

Because of the strict confidentiality required by the biopharmaceutical sector, we will’t identify any names. We’re, nonetheless, excited to be working with one of many largest suppliers of mRNA coronavirus vaccines.

Our first mission with this accomplice was probably the most thrilling initiatives for our engineering-to-order service so far. That is due to the time strain and the truth that the system we have been creating had by no means been produced earlier than.

The pressing want for the manufacturing of mRNA vaccines meant {that a} typical mission circulation – with planning, engineering, supply and order phases – couldn’t be used. Manufacturing started instantly following the primary request, while our engineers designed the system in parallel to manufacturing with our buyer.

Because of the fast-moving necessities of the mission, we needed to stay versatile. Typically work we had finished in the future wanted to be reversed or modified the next day. Following three months of extremely targeted growth, we have been proud to see the system in manufacturing.

It’s essential to say that our choices for the pharmaceutical business transcend our IJM Skids. We additionally present full options for the purification of different energetic pharmaceutical elements (APIs).

We are sometimes approached by clients who know their goal API and know the best way to produce it however lack the flexibility to purify it – that is the place KNAUER may also help.

When approached by such a buyer, we assist them from the underside up. We start with a column screening, then develop a way and optimize it on the lab scale. Utilizing these outcomes, we will then run the purification utilizing our simulated transferring mattress (SMB) system, which permits for steady purification.

Following this scale-up, our buyer can then start producing API at a pilot scale.

How does KNAUER assist GMP compliance for pharmaceutical producers?

KNAUER offers experience and assets to pharmaceutical producers to assist them implement GMP-compliant pharmaceutical manufacturing. Our clients usually have particular necessities for the KNAUER {hardware} that they’re considering, and these are often outlined of their particular Consumer Requirement Specs (URS).

We focus on the URS with our clients and assist be sure that their rules stay updated, serving to producers ship merchandise that meet their finish customers’ necessities and cling to all required security requirements.

Our GMP companies are primarily based on our {hardware} and software program options. Product security is supported by documentation on product conformity and the compliance of supplies used as wetted components.

High quality management is ensured by set up and operational qualification, in addition to efficiency verification. Moreover, a manufacturing unit acceptance check (FAT) and a aspect acceptance check (SAT) are commonplace GMP companies.

We additionally place a fantastic emphasis on private coaching, together with software program, {hardware}, upkeep and repair coaching packages.


Set up and testing of an IJM Skid for the encapsulation of API in lipid nanoparticles

What are a few of the new challenges that face the pharmaceutical business within the wake of the COVID-19 disaster, and the way will KNAUER assist sort out them?

From the COVID-19 disaster, we have now realized to be open to new applied sciences and that, for us, being quick and versatile are the keys to success.

In an even bigger perspective, there’s a chance that the coronavirus disaster has accelerated a fantastic change within the vaccine panorama – a migration to mRNA-based vaccines seems to be on the horizon.

mRNA vaccines have the distinctive benefit that they are often quickly modified in response to virus mutations, and this profit might see them starting to dominate the sphere within the coming years.

LNP-encapsulated mRNA expertise doesn’t cease there both – we count on to see the expertise being utilized in gene remedy, whereas LNPs, typically, can be utilized for the supply of different fragile APIs. We’re initially of a brand new period in drugs and we’re proud to be on the forefront.

We’re excited to be a part of this revolution and stay up for serving to drive this medical revolution with our tailored options for pharmaceutical processing and manufacturing.

How does KNAUER intend to work alongside customers in a post-COVID world?

We intend to work alongside customers as we did earlier than. For us, shut collaboration with our clients is the important thing to creating merchandise and programs that our clients are actually proud of.

We’ve got a devoted group of consultants from {hardware} development to high quality consultants obtainable all through the whole design course of, and these consultants are available to assist our clients with the experience they should discover one of the best answer to their challenges.

About Dr. Paul Pietsch

Dr. Paul Pietsch studied Meals Know-how on the Anhalt College of Utilized Science earlier than happening to finish a chemistry Ph.D. on the Technical College of Berlin. Following completion of his doctorate, Dr. Pietsch joined the group at KNAUER as a product supervisor for his or her steady chromatography programs. After 3 and a half years on this position, he moved on to turn out to be the pinnacle of engineering options throughout all the enterprise.




About KNAUER Wissenschaftliche Geräte GmbH

KNAUER Wissenschaftliche Geräte GmbH is a middle-sized firm that has been creating, manufacturing and distributing laboratory devices all over the world since 1962.

With greater than 130 workers, Knauer is without doubt one of the well-established producers of HPLC devices, SMB programs, and osmometers. Product portfolio consists of extraordinarily compact HPLC options, UHPLC programs for high-resolution evaluation, preparative HPLC devices, course of LC gear for the purification of gear within the kilogram scale, autosamplers, column thermostats, degassers, detectors, dosing pumps, eluent mixers, flowmeters, LC columns, and equipment and spare components, amongst others.

The supply of Knauer’s success is quite a few world’s firsts which have received greater than 20 awards for innovation.

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