When global demand for GLP-1–based therapeutics surged, our teams at TAPI faced an urgent challenge: to design and scale up a complex peptide process — from development through GMP manufacturing — faster than ever before. 

The result was a remarkable achievement: a state-of-the-art, fully automated production system built and qualified in record time, enabling delivery of high-quality material to meet global needs. But beyond the technical accomplishment lies a deeper story — one that reflects how TAPI operates as a CDMO partner: with agility, scientific depth, and an unwavering focus on collaboration. 

One Team, One Purpose 

From day one, our R&D and Operations teams worked as a single project unit, side by side on the shopfloor, united around one goal — bringing a new peptide to life for our customer. 

This integrated approach lies at the core of how we operate as a CDMO: by aligning science with execution, we ensure seamless tech transfer, accelerated timelines, and right-first-time delivery. 

Fast Response, Proven Expertise 

Introducing a new peptide product under extremely tight timelines required exceptional coordination and technical mastery. 

Leveraging decades of peptide experience and advanced process know-how, our cross-functional teams developed and scaled the process with speed, precision, and flexibility — repurposing equipment, optimizing systems, and implementing advanced analytical tools, all while maintaining full GMP compliance. 

The result: a fully qualified production system and a successful first GMP batch delivered on schedule — proving that agility and reliability can coexist, even in the most complex projects. 

Since then, the system has supported dozens of peptide batches — both for this product and additional molecules — demonstrating its robustness, scalability, and repeatability. 

Built for Flexibility and Performance 

Every element of the system was engineered with operational flexibility in mind. 
From in-house-developed purification systems to continuous concentration technology and solvent-recovery loops, innovation guided every decision. 

Operators were trained to perform real-time in-process controls (IPC) using HPLC and UPLC directly on the production line — increasing efficiency, reducing cycle time, and improving yield. 

Advanced Process Analytical Technology (PAT) and automation enable real-time process adjustments, ensuring consistent quality and minimizing variability. 
Today, our peptide production spans an impressive range — from below 5 all the way to tens of amino acids, across facilities capable of handling scales from a few kilograms up to 1.5-ton batches. 

These same technologies now underpin CDMO projects across multiple modalities at TAPI — from small molecules and peptides to HPAPIs and oligonucleotides. 

Innovation with Purpose: Sustainable by Design 

Sustainability guided this project from the start. 
The system integrates solvent recovery and recycling, energy-efficient emission treatment via RTO technology, and zero-discharge wastewater management — ensuring environmental responsibility without compromising performance. 

By combining process innovation with responsible manufacturing, TAPI continues to advance greener chemistry and help customers achieve their ESG goals. 

Partnership in Action 

This achievement embodies what TAPI brings to every CDMO collaboration: 

• One integrated team — R&D and Operations working as one. 

• Agility and speed — rapidly adapting to business needs and market timelines. 

• Operational flexibility — customizing systems and processes for each molecule. 

• Technical excellence — leveraging automation, PAT, and computational tools. 

• Sustainability commitment — embedding ESG values in every project. 

Through science, teamwork, and relentless drive, we turned a bold idea into a working reality — delivering value where it matters most: to our customers. 

Ready to Accelerate Your Program? 

At TAPI, we combine deep scientific expertise with global operational strength to help CDMO partners bring their molecules from concept to commercial reality — efficiently, safely, and sustainably. 

Learn more about our CDMO capabilities or reach out to our team to discuss your next project. 

Peptide-based therapeutics, especially GLP-1 agonists, have become essential tools in treating chronic diseases like type 2 diabetes and obesity. But behind their clinical promise lies a manufacturing challenge since peptide production is complex, sensitive to scale, and often resource-intensive. 

At TAPI, we’ve turned this into an opportunity. 

By embedding Process Analytical Technology (PAT) into every step of the peptide manufacturing process, we’ve developed a smarter and greener platform—already implemented at GMP scale—that elevates process control, accelerates timelines, and reduces environmental footprint. 

This innovation is a model for how we support CDMO partners with demanding peptide programs. 

A Holistic, Data-Driven Approach 

Peptide manufacturing is inherently intricate, with limited in-process monitoring options and high sensitivity to deviations. Our cross-functional R&D and engineering teams tackled these challenges head-on by implementing a comprehensive PAT framework across synthesis, purification, concentration, and lyophilization. 

Application of such real-time PAT tools include: 

1. Refractive Index (RI) and ultraviolet spectroscopy (UV) monitoring in Solid Phase Peptide Synthesis (SPPS): Used during coupling and deprotection, RI detects deviations in reaction completeness or reagent flow, while UV confirms Fmoc removal via characteristic absorbance. Together, they provide real-time insight into reaction progress and enable early intervention, improving sequence integrity. 

2. Conductivity monitoring in wash steps: In-line conductivity sensors measure residues and by products species such as dibenzylfulvene (DBF) and piperidine during resin washing, allowing dynamic wash control based on predefined thresholds. This eliminates unnecessary solvent use and enables DMF recirculation without compromising quality. 

3. Near-Infrared (NIR) spectroscopy for piperidine residue monitoring: NIR enables in-line quantification of residual piperidine, ensuring effective washing before each coupling step. This improves process readiness while reducing DMF use. 

4. Conductivity and NIR in downstream purification: Conductivity monitoring controls buffer preparation via in-line dilution and defines wash endpoints during desalting and ion-exchange. NIR enhances robustness, and in some cases serves as a real-time control for acetonitrile gradient accuracy in HPLC. 

5. UV monitoring in continuous concentration on a Wiped Film Evaporator (WFE): UV-based PAT tracks peptide concentration during evaporation using WFE (wiped film evaporation). Initially applied as at-line IPC, this was upgraded to in-line UV, achieving concentrations up to 100 mg/mL for GLP-1 peptide. This enabled efficient lyophilization while maintaining product homogeneity. 

6. Pressure monitoring in lyophilization. Dual pressure sensors (Pirani and Barocel) define robust drying endpoints independent of scale or load. This prevents overdrying, which was previously linked to peptide aggregation, ensuring product stability and process consistency. 

The result? Shorter cycle times, enhanced robustness, and right-first-time production—crucial benefits in a field where variability has long been the norm. 

Proven at Scale, Ready for Partnership 

This isn’t a lab-scale concept. Our PAT-enabled platform is fully operational in GMP manufacturing and has already demonstrated a measurable impact: 

• Reduced solvent and energy use 

• Minimized human error through real-time monitoring 

• Enhanced product consistency across batches and scales 

• A digital foundation for future AI and machine-learning integration 

Whether you’re looking to de-risk development, scale a late-phase peptide, or secure long-term commercial supply—TAPI brings proven capabilities, advanced infrastructure, and CDMO flexibility to the table. 

The TAPI Advantage for Complex Peptides 

With decades of peptide experience, dual-site GMP capacity in Israel and Croatia, and modular technologies (SPPS, LPPS, hybrid), TAPI is uniquely equipped to support partners from early development to commercial launch. 

As a CDMO, we don’t just offer capacity, we offer chemistry innovation, analytical depth, and strategic thinking. Our teams understand the nuances of peptides and work with you to design scalable, sustainable processes that meet your molecule’s specific needs. 

Partner with TAPI for Your Peptide CDMO Needs 

From GLP-1 agonists to custom sequences, we’re redefining what’s possible in peptide manufacturing. If you’re seeking a partner who blends cutting-edge technology with reliable execution, let’s talk. 

Contact us to explore how TAPI can support your next peptide program. 

At TAPI, advancing health from the core also means protecting the environment at the core of everything we do. Across our Teva Tech site, we’ve launched a bold initiative to transform sustainability from a checklist into a culture, embedding greener practices into every aspect of manufacturing. 

From Program to Culture 

In the past, sustainability lived mainly in the domain of EHS&S. Today, it’s a cross-departmental mission, driven by a dedicated site-wide sustainability team. By bringing together expertise from engineering, operations, production, and beyond, we’ve sparked new levels of engagement, creativity, and ownership. Every employee has the opportunity to contribute—and every idea matters. 

The goal? To be sustainable in sustainability—making continuous improvement an everyday mindset. 

Innovation Meets Responsibility 

Our cross-functional approach has already led to tangible improvements: 

• Energy efficiency: Installing variable frequency drives (VFDs), optimizing compressors, and upgrading chillers. 

• Leak detection with next-gen tools: Using thermal, 360°, and sound cameras to spot and eliminate hidden leaks in nitrogen, air, and steam systems. 

• Green electricity: Since April 2024, Teva Tech has been powered exclusively by renewable energy, with IREC certification in progress. 

• Zero-liquid discharge mindset: Real-time monitoring of emissions, advanced wastewater treatment, and solvent recovery built into every new product. 

• Paperless production: Piloting electronic batch records to eliminate paper use and streamline compliance. 

• Smarter waste management: Campaigns for separation and recycling of plastics, metals, batteries, and more. 

These projects are designed not only to reduce energy, water, nitrogen, and steam consumption by 5–15% per year, but also to ensure measurable reductions in Scope 1 & 2 GHG emissions. 

A Win for Customers and Communities 

For our customers, sustainability is a shared priority. By reducing GHG emissions in all our sites in TAPI, we are helping our partners to achieve their ESG targets. At the same time, our initiatives strengthen supply reliability, reduce costs, and ensure compliance with local and global regulations. Beyond numbers, this program is shaping how our people think, act, and innovate. Every new project now runs through the lens of sustainability, making greener operations our standard way of working. 

Looking Ahead 

We see this as just the beginning. From exploring on-site energy storage to scaling AI-enabled monitoring systems, the journey to a greener future is ongoing. Most importantly, sustainability at TAPI is no longer just a department, it’s a shared responsibility and a source of pride. 

As a provider, partner, and pioneer, we are setting a new benchmark for green API manufacturing — one that benefits our industry, our customers, and the communities we live in. 

In pharmaceutical development, the race to bring medicines to patients faster—without compromising on quality—is more critical than ever. At TAPI, we’re answering that challenge head-on with an innovative platform that transforms how solid forms are identified and developed. By integrating computational tools with high-throughput laboratory automation, we’re not just streamlining solid-state R&D—we’re reshaping it. 

Rethinking Polymorph Screening 

Solid form matters. Polymorphs, hydrates, solvates, and amorphous structures may influence a drug’s solubility, stability, manufacturability, and regulatory path. Traditionally, uncovering these forms has relied on labor-intensive, trial-and-error methods. Our bespoke platform reimagines this process by combining computational tools modeling with smart experimental design. 

We leverage tools like Crystal Structure Prediction (CSP), lattice energy ranking, and targeted screening algorithms to identify different solid forms. Our unique approach allows us to creatively design the experimental plan before we even step into the lab—saving time, materials, and energy. 

From Prediction to Precision: Smart Experimentation in Action 

Our software-based systems are fully integrated with  automated high-throughput polymorph screening (HTPS). This means that parallel experimentation with multiple crystallization conditions can be conducted faster and more systematically than ever before. Using tools like PXRD, DSC, TGA, and microscopy, we can rapidly identify and characterize different solid forms with scientific rigor. 

And thanks to a closed-loop feedback system, experimental data feeds back into the AI models—making them smarter over time and improving accuracy with every iteration. 

Impact That Scales 

This is more than a lab breakthrough—it’s a platform with real-world impact. By enabling earlier identification of optimal solid forms, we help pharmaceutical partners minimize late-stage surprises, improve formulation robustness, and accelerate regulatory submission. It’s a smarter, safer, and faster way to advance drug development. 

A New Standard for Solid-State Innovation 

At TAPI, science is strength—and our innovative platform embodies our passion for advancing health from the core. By combining digital intelligence with expert intuition, we’re enabling our partners to make better decisions, faster. It’s not just innovation—it’s transformation. 

Whether you’re formulating a first-in-class therapy or optimizing a generic molecule, our AI-powered solid form platform is ready to support your journey. 

Let’s move beyond what’s expected. Let’s redefine what’s possible. 

At TAPI, we are dedicated to advancing sustainable pharmaceutical manufacturing by harnessing the power of cutting-edge science—particularly biocatalysis. One of our recent successes exemplifies this commitment: the development of a scalable, environmentally responsible biocatalytic process for the production of a complex chiral intermediate used in the synthesis of Avacopan. This achievement not only overcomes long-standing challenges in stereoselective synthesis; it also demonstrates the broader potential of enzyme-based technologies to streamline pharmaceutical production. 

By integrating biocatalysis into our development workflows, we offer innovative, greener alternatives to traditional chemical routes—delivering benefits in efficiency, selectivity, and sustainability. These capabilities are now a core part of our value proposition, both for our internal portfolio and for partners through our CDMO services. Whether optimizing existing processes or designing new synthetic pathways, we are helping to redefine what’s possible in pharmaceutical manufacturing through biocatalytic innovation. 

The Challenge: Double Stereocontrol with High Yield and Low Waste 

The synthesis of 2,3-disubstituted cyclic amines — especially with full control over two adjacent stereocenters — has historically been a significant challenge in API development. Traditional chemical synthesis routes for Avacopan’s (2R,3S)-2-arylpiperidine-3-carboxylate intermediate rely on diastereomeric crystallization, a process that discards nearly half of the material and yields only 42%. 

We saw an opportunity to develop a cleaner, more efficient alternative. Inspired by the principles of green chemistry, our team sought a stereoselective, biocatalytic solution that could reduce waste and improve scalability. 

The Solution: Enzyme-Catalyzed Amine-Imine Transformations 

Through extensive enzyme screening, we developed two innovative routes using imine reductases (IREDs): 

1. Oxidative kinetic resolution of the racemic amine, followed by catalytic hydrogenation for enantiomer recovery — successfully scaled up to kg scale. 

2. Dynamic kinetic reduction using enantiocomplementary IREDs — demonstrated at lab scale, showing strong potential for further development.

These pathways hinge on the reversible imine-enamine tautomeric equilibrium, which allows for efficient recycling of undesired stereoisomers and high selectivity toward the desired (2R,3S)-configured intermediate. 

Key Innovations 

• Enzyme Selection and Cofactor Regeneration 

We identified four commercial IREDs capable of enantioselective oxidation and two others for dynamic kinetic reduction. However, to make the process robust and scalable, we also needed an efficient system for cofactor regeneration. 

Traditionally, NADPH oxidases (NOx) were used for this role but posed challenges due to their sensitivity to solvents. Our breakthrough came with the application of alcohol dehydrogenase (ADH) enzymes — specifically from Lactobacillus brevis — as a more stable and scalable alternative for cofactor regeneration. This was the first reported use of ADHs in IRED-catalyzed oxidations, marking a significant step forward in biocatalysis. 

• High Selectivity and Improved Yields

Our enzymatic process achieved exceptional selectivity: 

• Oxidative route: >99.5% ee and >99.9% de 

• Reductive route: 98.3% ee and >99.9% de 

The oxidative route also significantly improved overall yield. By coupling it with a catalytic hydrogenation recovery step, we reached 72% yield across cycles — a dramatic improvement over the 42% achieved by conventional crystallization. 

• Scalable, Safe, and Sustainable 

Safety and scalability were paramount. Unlike earlier methods using monoamine oxidases and hazardous reducing agents (like boranes), our enzymatic routes avoid incompatible chemicals. The oxidation process was safely scaled to kg levels, with a high space-time yield of 37.2 g/L/day — a strong metric for industrial viability. 

In terms of sustainability, the use of biodegradable enzymes, mild conditions, and minimized waste supports our commitment to environmentally responsible API production. 

A Model for Future Development 

Our biocatalytic model provides a practical framework for innovation in pharmaceutical manufacturing, tackling issues that rise from a standard chemical synthesis approach: 

• It illustrates how the stereo controlled synthesis of complex amines can be achieved efficiently using green chemistry, addressing a long-standing synthetic challenge. 

• It expands the perceived role of ADHs by demonstrating their effectiveness in oxidation reactions, opening new avenues within biocatalysis. 

• It highlights how enzyme-driven processes can achieve both economic scalability and environmental responsibility—two critical priorities for the industry. 

Partnering for Innovation: CDMO Services at TAPI 

This breakthrough in the synthesis of Avacopan API exemplifies how targeted innovation, grounded in green chemistry principles, can transform pharmaceutical manufacturing. With better yields, reduced environmental impact, and strong scalability, this process is not just a milestone for TAPI — it’s a glimpse into the future of sustainable use of biocatalysis in pharmaceutical manufacturing. 
 
This achievement reflects more than scientific innovation—it demonstrates what’s possible when advanced technologies meet end-to-end CDMO support. At TAPI, we offer integrated CDMO services across every stage of development, from route scouting and process design to scale-up, GMP production, and commercial supply.  

Our global network spans 13 manufacturing sites and 5 R&D centers, supported by ~450 scientists and a deep toolbox of enabling technologies—from biocatalysis and flow chemistry to particle engineering and ultrafiltration. Whether your program involves small molecules, peptides, oligonucleotides, fermentation products, or HPAPIs, we’re ready to tailor solutions that accelerate your success. 

Fermentation is at the heart of many life-saving medicines. But when it comes to large-scale production, it’s one of the most unpredictable and complex processes in pharmaceutical manufacturing. At TAPI, we’ve taken a bold step toward solving this challenge—by combining data science, automation, and our deep process expertise to revolutionize how we manage substrate feeding in fermentation. 

The Challenge: Complexity in Every Drop 

As a global leader in active pharmaceutical ingredient (API) production, TAPI has a long-standing tradition of excellence in fermentation. Our largest fermentation site, based in Hungary, handles some of the most technically demanding production processes. These processes involve living organisms, over 200 hours of process time, and highly sensitive multi-variable conditions—all of which can lead to unpredictable yields and inefficiencies. 

One of the biggest variables? Substrate concentration. It needs to be maintained within an extremely narrow range throughout the entire process, which is no easy task with such complexity in play. 

The Solution: Smarter, Safer, and More Sustainable 

To meet this challenge head-on, we partnered with a specialist in process control to develop and implement an automated substrate feeding strategy. The result: a cutting-edge system powered by big data analytics, real-time prediction (via a “soft sensor”), and continuous concentration control. 

Key highlights include: 

• Real-time control: The system calculates and adjusts the substrate dosage rate automatically, removing the need for manual sampling and reactive adjustments. 

• AI-driven prediction: A soft sensor uses production data to predict substrate levels, enabling proactive decision-making. 

• Seamless integration: The algorithm was designed to fit into existing systems without disrupting ongoing operations. 

This wasn’t just a theoretical exercise—the system is live and delivering results. 

The Impact: Greater Efficiency, Lower Carbon Footprint 

Since implementing this control strategy, we’ve seen over a 15% increase in productivity, while simultaneously reducing our carbon footprint. By keeping substrate levels consistently optimal, the system minimizes fluctuations and improves reproducibility—two major pain points in any fermentation process. 

And the best part? This approach is scalable. The same control model can be tailored and applied to other fermentation processes across our sites, unlocking even broader improvements. 

Looking Ahead: A New Standard in Bioprocess Control 

What sets this development apart is not only the technology—but the mindset behind it. We’ve shown that internal know-how, combined with external collaboration and smart data use, can lead to real operational transformation. With this innovation, TAPI is setting a new benchmark for how fermentation can be controlled: more precise, more consistent, and more sustainable. 

This is just one example of how we’re advancing health from the core—by optimizing the very processes that make modern medicine possible. 

At TAPI, advancing health from the core doesn’t only apply to the products we manufacture, it also shapes how we operate. Safety is a fundamental ingredient in our processes, and continuously improving how we identify and manage risk is key to that mission. As part of our evolving Process Safety Management (PSM) program, we recently delivered an in-depth training series focused on the new global guideline for Hazard and Operability Studies (HAZOP). 

This new HAZOP procedure—GDE-05-513.01—is a critical tool to strengthen risk awareness, hazard identification, and cross-functional alignment. The training was designed not only to reinforce the new methodology, but also to embed it effectively across TAPI’s operational, technical, and safety communities. 

A Tiered Training for Targeted Impact 

The program was structured into two distinct training paths to meet the needs of different stakeholder groups: 

• Core 2-Day Training (8 hours each day): This deep-dive track was delivered to EHS managers and specialists, HAZOP facilitators, process safety managers, and project engineers—those responsible for initiating, leading, and guiding HAZOPs in high-impact scenarios. The sessions covered all elements of the updated procedure, including facilitation techniques, risk ranking using TAPI’s proprietary matrix, and documentation best practices. 

• 3-Hour Awareness Session: Aimed at regular HAZOP participants from our sites, including MS&T, operations, maintenance, and instrumentation teams. This session introduced the methodology, roles and expectations, and the rationale behind the updated approach, ensuring stronger participation and understanding during future studies. 

Both sessions focused on creating a consistent, compliant, and collaborative risk review culture across TAPI. 

What’s New in the HAZOP Standard 

HAZOP is a structured team-based method to systematically evaluate deviations from intended process conditions and identify risks before they materialize. The new standard outlines a detailed, step-by-step methodology that brings several enhancements to our previous approach: 

1. Stronger Team Composition & Roles 

The updated guideline defines clear competency-based roles for each participant, including the HAZOP Facilitator, Scribe, Process and Instrumentation Engineers, EHS professionals, Operators, MS&T specialists, and even vendor representatives. The training emphasized how each of these voices brings critical insights to ensure a comprehensive evaluation. 

2. Defined Risk Assessment Criteria 

Participants were trained on TAPI’s risk matrix methodology, which combines likelihood and severity to generate a quantifiable risk score. The matrix includes specific thresholds for “Acceptable,” “Tolerable (ALARP),” and “Unacceptable” risks, helping teams prioritize follow-up actions and investments. 

3. Barriers, Safeguards, and the ALARP Principle 

The new training also clarified how to assess the validity of safeguards, known as barriers. To be considered valid, a barrier must be effective, independent, and auditable. For example, operator actions can only be considered safeguards under strict timing and training conditions. Additionally, the ALARP (As Low As Reasonably Practicable) concept was explored in detail for medium-risk scenarios—providing a defensible framework for when additional controls may no longer be justified. 

4. Documentation and Closeout 

An important part of the new guideline is ensuring clear, traceable documentation. Participants were guided through the new HAZOP Worksheet template, which captures deviations, causes, consequences, safeguards, and recommendations. The follow-up process—including assigning action owners, using tracking tools, and reporting progress to site leadership—was also emphasized. 

Online Access via Process Safety (PS) Academy 

To support long-term learning and implementation, the content from this training will soon be available as digital learning modules on the PS Academy platform. This enables easy access for onboarding new team members, refreshing knowledge, and fostering a consistent global safety culture. 

Why It Matters 

A well-executed HAZOP doesn’t just meet compliance—it actively prevents incidents. It is one of the most powerful tools we have to protect people, products, and the planet. By investing in deeper training and applying a standardized global methodology, we’re reinforcing our commitment to excellence in every facet of operations. 

At TAPI, safety is a shared responsibility. This training equips our teams to uphold that responsibility, bringing science, rigor, and teamwork to the forefront of every process. 

At TAPI, innovation drives everything we do—from early development to commercial scale. Crystallization is one of the most critical steps in API manufacturing, and gaining control over this process is key to achieving consistent critical quality attributes (CQAs), such as polymorphic form and particle size distribution. 

Traditionally, crystallization monitoring has depended on offline sampling, a time-consuming and complex approach that limits real-time insights and hinders process optimization. To overcome this, our R&D team implemented in-line process analytical technology (PAT) tools to solve a specific and scientifically challenging crystallization issue during the development of a novel API sulfonate salt. 

The challenge? A late-appearing polymorphic form—an industry-recognized risk with major implications for product consistency and performance.  

Leveraging Blaze high dynamic range (HDR) process microscopy in tandem with Raman spectroscopy, our scientists achieved rapid root-cause identification and developed a robust new crystallization process—demonstrating the power of real-time PAT integration. 

From Insight to Impact: Background & Approach 

During the first kilo-lab scale-up of the sulfonate salt, a new polymorphic form unexpectedly emerged—despite extensive prior screening. To tackle this, our team deployed advanced PAT tools, including HDR microscopy and Raman spectroscopy, for in situ monitoring of particle statistics and polymorphic transitions. 

This data-driven approach allowed rapid, informed decision-making and accelerated the development of a new crystallization process. 

Why PAT Makes the Difference 

The Blaze 900 system integrates HDR microscopic imaging, turbidity measurement, and Raman spectroscopy into a single, multi-functional probe. Its advanced image analysis algorithm provides accurate particle statistics—significantly outperforming conventional tools like PVM and FBRM. 

This capability enables real-time tracking of key crystallization phenomena, including nucleation, growth, attrition, oiling out, and polymorphic transformations—driving deeper process understanding and control. 

Overcoming the Polymorphism Challenge 

Lab investigations revealed that the anhydrous form of the compound could rapidly convert into either a monohydrate or a newly discovered methanolate, depending on the solvent system. These two novel forms, each with distinct crystal habits and thermal behaviors, were shown to be in an enantiotropic relation. 

With direct crystallization of the anhydrous form no longer feasible, our team pivoted to explore seeded cooling crystallization to obtain the monohydrate.  

This was followed by extensive Raman-supported solvent screening to enable a solvent-mediated polymorphic transformation into the desired anhydrous form—unlocking valuable insight into conversion kinetics. 

A Smarter, Faster Path to Process Development 

The integration of HDR microscopy and Raman spectroscopy enabled precise identification of transition points and streamlined the development of a robust crystallization pathway. This not only reduced development time but also improved product quality and ensured more reliable process control—highlighting the strategic value of in-line PAT. 

The combination of Blaze 900 in-line process microscopy with Raman spectroscopy marks a significant step forward in crystallization process development. By enabling real-time, in-depth process insight, these tools reduce reliance on offline analytics, accelerate development, and strengthen product robustness. 

At TAPI, we continuously invest in advanced technologies to drive smarter, faster, and more reliable API development—empowering our partners with solutions that deliver measurable impact. 

We’re proud to share our recent peer-reviewed scientific article, published in the prestigious ACS Organic Process Research & Development journal, titled “Imine Reductase-Catalyzed Synthesis of a Key Intermediate of Avacopan: Enzymatic Oxidative Kinetic Resolution with Ex Situ Recovery and Dynamic Kinetic Reduction Strategies toward 2,3-Disubstituted Piperidine.”

This milestone underscores the strength and innovation of our R&D team and marks TAPI’s presence in the global scientific community as a thought leader in process chemistry.

In this article, our scientists demonstrate the ability of proprietary imine reductases (IREDs) to control the configuration of two vicinal stereogenic centers in avacopan API via oxidative kinetic resolution. The system involves selective oxidation and tautomerization of the undesired enantiomer into a corresponding enamine. This byproduct is then either recycled via catalytic hydrogenation back to the racemic starting material or transformed through a dynamic kinetic resolution using another proprietary IRED with excellent diastereoselectivity. 

The process was successfully scaled to the kilogram level, with outstanding selectivity and yield. It’s an excellent example of how TAPI combines biocatalysis and process innovation to deliver efficient, sustainable solutions to complex synthetic challenges. 

Access the full article here.