Flow Tech.

Flow Technology

CONTINUOUS FLOW TECHNOLOGY

A Chemical manufacturing revolution

There may be more sense to recent technology movements than you think

INTRODUCTION

Chemistry has over the decades been able to develop very complex transformations in order to produce multifunctional molecules. Despite these important advances, we are still using round bottom flasks and batch reactors to perform such transformations as 200 years ago. 


Continuous flow synthesis, also known as flow chemistry technology is an innovative technology in which chemical reactions are performed in continuously flowing streams within narrow channels. Until recently, the flow technology was the right choice only for very large systems, with low degree of complexity or chemical sophistication, such as petrochemicals.


Correlated with disruptive manufacturing technologies, such as metal 3D printing, flow chemistry is changing the way we do synthesis today in lab and in industrial scale. Complex and regulated industries such as the pharmaceutical industry are taking advantages of this technology to become more integrated, to develop more efficient processes and to reduce timelines from drug discovery to the market. 

Movie Courtesy by CSIRO  https://www.csiro.au

ADVANTAGES

There are intrinsic changes and advantages of using narrow tubes as reactors to perform chemical synthesis. One of the most direct changes in this type of reactors, is the high surface-to-volume ratio, translated in practical therms as efficient mixing (micromixing) and ultra-fast heat transfer. Those characteristics together take process control of reaction parameters, such temperature and pressure, to a new level, enabling the adoption of fully automated plants with minimum effort.


Using better mixing coefficientts and fast heat transfer, the overall kinetics of reactions also changes towards efficiency. Sometimes, the improvement on that is so significant that we can speed up reactions by a factor of 1000; converting 48hs of intensive batch mixing into 3 minutes of tube residence, reducing a 250 sq m facility to a 14 sq. m portable containers.

Comparison between Batch and Continuous Flow process:

Batch Process

  • 2 steps reaction
  • >700 min. of total reaction time
  • 91% overall yield
  • 3 unit operations
  • Reactors Factor of Scale = 1
  • External Hidrogen supply

C. Flow Process

  • 1 step reaction
  • < 2 min. of total reaction time
  • 99% overall yield
  • 1 unit operation
  • Reactors Factor of Scale = 1/15
  • In-Situ Hidrogen generation

APPLICATION AND REGULATION

How far along is the technology? What are the constraints under regulated products? Is flow chemistry safety enough to produce medicines? What are the practical projects using flow regime?

Some questions can arise in the way to develop and apply disruptive technologies such as flow chemistry and this is normal.  If we were in 2015, we could not answer some of those, and they could be classified as risk factors for projects, but this is not the reality anymore.


Many projects are arising worldwide as the time flow chemistry is advancing. From well know universities, such as MIT, to a reference research institutes, such as Max Planck, flow chemistry is blooming and proving its advantages. Since 2013, big pharma companies such as Pfizer, Merck, Janssen, Lonza, Eli Lilly and Novartis are financing and approving their own projects based on flow processing, not only for the chemical synthesis steps, but also for drug formulation and packaging steps.


Through the prism of regulation, in June 2018, the International Council for Harmonization (ICH) announced in a press release the new Guideline ICH Q13 to support the introduction of continuous manufacturing into the pharmaceutical industry, and several efforts are taking places worldwide to support this initiative. By December 2020, the United States Food and Drug Administration (FDA) approved continuous manufacturing of six finished drug formulations as innovative products.


A FUTURE OF OPPORTUNITIES

The flow chemistry market reached $1.2 billion in 2018 and is expected to value $2.9 billions by the year of 2026, with a solid 11.3% CAGR. As the time flow synthesis can squeeze buildings for batch facilities under a portable container sized solutions, the advantage using this type of production is becoming more and more evident.


The Barda agency in the USA announced in May 2020 investments on flow technology starting in $354 million–with the potential to increase to $814 million– on new companies using advanced manufacturing technologies. The main objective is to boost the development of chemical compounds for active pharmaceutical ingredients,  avoiding or addressing drug shortages amid the coronavirus pandemic. Aimed at reducing America’s reliance on API (active pharmaceuticals ingredients) imports from countries such as India and China, the U.S. International Development Finance Corporation (DFC) approved loans to Kodak in September 2020 to invest over $765 millions in new technologies to produce generic APIs for the US market.


The inherent capacity of flow chemistry to reduce CAPEX and operational costs to a fraction, and to speed up processes and the suitability to take advantage on fully automated facilities, can lead flow chemistry towards a safer, cleaner and cheaper future than batch processing.


Flow chemistry technology represents today, not only a bright future for chemical synthesis, but also represents an opportunity for underdeveloped countries to build their industrial bases and become self-sufficient regarding their needs for specialty chemicals, from basic pesticides for agriculture to complex molecules to support their basic health system, such as active pharmaceutical Ingredients (API's).

A not so silent revolution is under way...

"A coming revolution is continuous flow chemical manufacturing, in which compact, continuous flow reactors promise far more efficient reaction processes."

flow chemistry

Jul 29, 2020

"Development Authority (BARDA) awarded Phlow a $354 million contract, with which it plans to build a so-called fill-and-finish plant, which combines APIs and other nonactive ingredients"

investment in flow

Jun 29, 2020

“The majority of chemistry hasn’t changed from the way we’ve been doing it for the last 200 years. It’s very manual, artisan driven process, (...) There’s billions of dollars of opportunity there.”
"Adam Boehler will today sign a letter of interest (LOI) to provide a $765 million loan to Eastman Kodak Company (Kodak) to support the launch of Kodak Pharmaceuticals"

supply assurance

Jul 29, 2020

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