EOS Med Chem, Medicinal Chemical is Big: EOS Med Chem World TOP 11 Technology, meet China CPHI

This is my R&D youtube: https://youtu.be/r5cJdXKNXHk

FDA New, GMP Do

Clinical Phase II, III Intermediates

GMP Custom synthesis, Full Document

R&D Center: 8000 sq, More than 100 hoods

Pilot Plant: 20000sq, 40 reactors from 5-200L

Manufacturing Site: 800000sq, 40 reactors from 100-5000L

Web: www.eosmedchem.com

Email: info@eosmedchem.com; eosmedchem@gmail.com

EOS is a trusted partner that can provide commercial products. We have established comprehensive commercial production factories and facilities to support various aspects of the supply chain from raw material procurement to finished product export. R&D staff full-time 45, 10 visiting professors, 1 national special allowance.

EOS has reliable commercial production and pilot production partners and can provide true "one-stop" services from early research and development to commercial production. Our equipment can realize pilot scale amplification of various types of reactions including asymmetric hydrogenation reactions, air and water-sensitive metal-catalyzed reactions, high temperature, high pressure, low temperature and oxidation reactions, hydrogenation, and fluorine, ozone, format reaction addition.

Flow Chemistry 1

Fluorination 2

Asymmetric Synthesis 3

Chiral Synthesis 4

Hazardous Reactions 5

Low Temperature 6

Highly Potent 7

Non-Precious Metal Catalysis (NPMC) 8

High-Pressure Chemistry 9

Electrochemistry 10

Photochemistry 11

Sustainable Access to Drug Substance

Over the last ten years, EOS MED CHEM has led our flow chemistry service solutions and developed multiple platforms and processes. The resulting mastery of “end-to-end” continuous flow production allows our team of specialized scientists and engineers to fabricate new reactors and develop robust processes to match reaction requirements. These solutions offer customers multiple advantages including improved safety and efficiency, space savings, increased production capacity, and paired with in situ reaction monitoring.

To date, EOS MED CHEM has developed platforms for process screening, equipment especially designed for process validation and prototype reactors. Applying these advances, we’ve been able to easily judge flow reaction feasibility, transfer new technology to production, and scale-up applications quickly — all while applying GMP requirements.

Reaction Types

·Cryogenic reactions (≤ -20ºC)

·High temperature reactions (≥ 150ºC)

·Diazomethane reactions

·Ozonation reactions

·Oxidation with peroxide

·Nitration

Process Development Solutions

·Process Development Solutions

·Flow-chemistry feasibility assessment

·Process development and optimization

·Validation and up-scaling

·Model design (new technology platform)

Organic fluorides are crucial in pharmaceutical industry. Nearly one fifth of the newly marketed drugs contain fluorine. Fluorinated drugs are usually more efficient on the targeted organs because of better membrane penetration and higher bioavailability, which results in lower daily drug dosage. EOS Med Chem has applied the technology in the syntheses of key intermediates of sofosbuvir and riociguat, as well as spiro, four-, five- and six-membered rings.

EOS Med Chem takes advantage of a large tool kit of chiral catalysts, ligands and auxiliaries etc., to develop asymmetric syntheses of building blocks. Asymmetric synthesis is effective to cut down production costs, improve reaction efficiency, and reduce wastes and energy consumption per unit of output.

·Asymmetric reduction

·Asymmetric kinetic resolution

·Asymmetric addition

·Asymmetric fluorination

Customization, Flexibility, and Expertise

Enantio-selective synthesis provides access to biologically active small molecules within the pharmaceutical industry. We offer custom synthesis of chiral molecules through separation of racemic material as well as modern asymmetric synthesis. Our team of experts provides catalyst screening as well as multi-step synthesis from a few milligrams up to metric tons.

·Chiral Synthesis Services

·Asymmetric induction

·Chiral pool

·Organocatalysis

Managing Safety Concerns at Scale

While certain chemical reactions by their nature are hazardous — especially when scaled up — we’re committed to applying innovative techniques to manage safety concerns. Continuous flow chemistry — a core technological focus here at EOS MED CHEM — is the ideal solution to such manufacturing hazards. Over the last decade, our experts have successfully developed novel flow processes for a variety of typical hazardous reactions on clinical and commercial supply scales with in-house designed equipment.

Whether in batch or continuous flow, EOS MED CHEM performs a complete hazard assessment prior to scaling a process involving hazardous chemistry to ensure safe operation. Our Process Safety Lab performs thermal screening and calorimetry to understand thermal hazards of the chemistry, thermal and mechanical stability testing of product, and other process-related hazards such as vent sizing determination to understand engineering requirements for processes that generate gases. All processes that are scaled undergo a rigorous HAZOP process to ensure safe operation.

Capabilities and Advantages

·Dedicated Process Safety Lab equipped to assess thermal and mechanical risks of hazardous reactions (i.e. DSC, TSu, ARC, RC1, Fall Hammer).

·Strong EHS culture to ensure safety of people and environment.

·Track record of operational safety and regulatory compliance.

·Manufacturing equipment with engineering controls designed for running processes that involve hazardous reactions.

·Experience with hazardous chemistries in both batch and continuous flow such as reactions using diazomethane and azide reactions, ozonation, nitration, and processes using reactive gases.

Production Scale Cryogenic Processes: Batch or Continuous Flow

EOS MED CHEM has gained years of experience in process development, scale-up, and manufacturing where cryogenic reaction conditions are required, such as Grignard reactions and metal-halogen exchange. We have batch reactors up to 8000 L scale capable of temperatures to -90°C. Our cryogenic manufacturing can be performed using continuous flow technology which offers improved temperature control, energy efficiency, and safety profiles for cryogenic reactions.

Low Temperature Capabilities and Features

· Capability to perform cryogenic batch chemistry at pilot to commercial scale at all three manufacturing hubs within the organization.

· Experience at amending traditional batch cryogenic processes to continuous flow which offer superior heat transfer efficiency and is less energy-intensive. (link to flow page).

·Commercial scale cryogenic continuous flow capabilities at temperatures as low as -110°C.

·End-to-End; flow reaction +continuous workup.

·Process built on modularity (operational units on skids)

·Flexibility and robustness.

·Use of paired portable tanks to insulate process from disturbances and provide flexibility to operations to react in case of process upsets.

·Real-Time Monitoring.

·Use of PAT to ensure steady state at key points of the process and guarantee quality of product.

Technology to Handle Toxic Chemicals With Care

Everything about our Highly Potent Active Pharmaceutical Ingredients (HPAPIs or HPAIs) compounds capabilities is designed to reduce the risk posed by these toxic substances. Our facilities focus on both GMP and non-GMP configurations, including common potent compound classes (β-lactam). We’ve configured our equipment to maximize flexibility and developed processes to eliminate contamination vectors, like pressurization. Plus our primary decontamination stations within suites are situated to make sure that we maintain qualification by continually training employees on best practices.

HPAI Capabilities

·Medicinal chemistry

·API manufacturing

·Drug product manufacturing

Cost-saving, Sustainable Alternatives for Coupling Reactions

The precious metals typically used as catalysts in pharmaceutical manufacturing — palladium, platinum, rhodium, and ruthenium — keep costs high and efficiencies low. Working in-house and in collaboration with industry and academic leaders, we have formed the NPMC Consortium to address these concerns. Working together we’ve developed processes and procedures that use non-precious metal catalysis (NPMC) to challenge cost, abundance, sustainability, and waste inefficiencies.

EOS MED CHEM NPMC Benefits

·Active research into less expensive catalysts or enzymes for catalysis.

·Ni-catalyzed reductive coupling.

·Extends to heterocycles and functionalized alkyl halides.

Leveraging Experience from Modeling to Manufacturing

API manufacturing often takes advantage of high pressure chemistry — those reactions involving a gas as a reagent such as catalytic hydrogenation. At EOS MED CHEM we’ve spent considerable time establishing a dedicated research team and building significant capacity at our two main API manufacturing sites to support this core technology. Our 300-3000L autoclaves are rated at 4-9 MPa, and are stainless steel and Hastelloy.

·Well equipped R&D facility with parallel screening equipment and bench-scale autoclaves.

·Reaction modeling for efficient transfer to manufacturing scale.

·Extensive and redundant large-scale manufacturing capacity.

·Experience adapting batch high pressure processes to continuous flow.

Services & Capacities

·Microscale experimental techniques (1-10 mg）.

·Small-scale pilot simulation.

·48 vial Parallel screening.

·24 vial scaling-up screening ability.

·Reaction kinetics measurement.

·Small pilot workshop.

·Full equipment kLa data set up, which maintains constant pressure automatically.

·Automatic data collection (Hydrogen absorption kinetics can be realized).

Sustainable Solutions Including R&D and Scale Up

As part of our commitment to green chemistry and industry collaborations, EOS MED CHEM has developed extensive electrochemistry capabilities. By conducting lab-based feasibility studies, we can determine whether a redox can be done electrochemically and whether it’s feasible for scale up. Each scope includes selection of appropriate cathode and anode, electrolyte, and other conditions such as concentration and applied voltage. In addition we can manufacture large quantities using flow cell technology.

Advantages

·Alternative to traditional reduction/oxidation reagents that are toxic, expensive and not environmentally friendly

·Access to chemical transformations not traditionally available through typical chemistries

·Reactivity can be “dialed-in” to achieve improved chemoselectivity

·Aceration of redox steps in a complex catalytic cycle possible

Equipment