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. 

TAPI and Antheia have announced a new strategic partnership designed to support the commercialization of Antheia’s biosynthetic key starting materials (KSMs) and active pharmaceutical ingredients (APIs). Antheia will leverage TAPI’s next-generation fermentation capabilities and manufacturing facilities in Europe to scale its pipeline and accelerate time to market for future product launches.

This collaboration combines Antheia’s innovative biosynthesis platform with TAPI’s advanced bioprocessing and manufacturing capabilities. The existing infrastructure, capacity, and quality management systems TAPI provides are well suited for Antheia’s processes, enabling efficient, reliable, and high-quality production at commercial scale. The partnership is positioned to support multiple products in Antheia’s pipeline and strengthen the long-term commercialization strategy.

With nearly a century of API manufacturing experience, TAPI offers the expertise and state-of-the-art infrastructure needed to support Antheia’s mission to transform pharmaceutical supply chains and advance essential medicines.

This collaboration reflects TAPI’s role in bringing scientific innovation and manufacturing excellence together. Through a flexible tech-transfer model and a collaborative, problem-solving approach, TAPI will support Antheia’s biosynthetic platform with advanced fermentation and enzymatic capabilities that help make these complex processes commercially viable.

To read the full announcement, click here: Antheia and TAPI Partner to Advance Global Commercialization Strategy for Critical Pharmaceutical Ingredients

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, 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. 

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.

In today’s rapidly evolving pharmaceutical landscape, a robust, flexible, and globally diversified manufacturing network is more than just an asset—it’s a strategic imperative. At TAPI, we leverage our worldwide presence to offer unparalleled Contract Development and Manufacturing Organization (CDMO) services. Our expansive network spans North America, Europe, Asia, and the Middle East, ensuring that your supply chain remains continuous, secure, and responsive to your unique needs. 

A World-Spanning Network of Manufacturing Excellence 

TAPI’s success is built on a foundation of geographic diversity and deep-rooted local expertise. Our manufacturing facilities are strategically located in key regions—including Mexico, several European hubs, India, and Israel—to provide you with a truly global service. This extensive footprint means that whether you need early starting materials, intermediates, or finished products, TAPI can source the raw materials and deliver products from the most efficient and cost-effective locations around the world. 

Ensuring Supply Chain Continuity and Security 

One of the primary challenges in pharmaceutical manufacturing is ensuring that the supply chain remains resilient against unforeseen disruptions. At TAPI, our diversified manufacturing sites are a cornerstone of our strategy to mitigate risks. By operating in multiple regions, we ensure that your projects benefit from: 

• Supply Chain Security: Multiple manufacturing sites reduce dependency on a single region, enhancing continuity and minimizing risks. 
• Dual Sourcing: Many of our customers appreciate the advantage of having at least two sources for critical components, safeguarding against potential supply bottlenecks. 
• Adaptability: Our global network allows us to swiftly adapt to changes in the market or regulatory environment, ensuring your supply chain remains robust and reliable. 

Harnessing Local Expertise and Advanced Technologies 

At TAPI, each of our global manufacturing sites is a hub of specialized expertise, equipped with advanced technology and tailored capabilities to meet your unique needs. Our diverse network ensures that every production process—from early-stage development to commercial-scale manufacturing—benefits from local excellence and precise technological solutions. For example, our specialized capabilities include: 

• Peptides & Oligonucleotides:P We produce complex peptides (GLP-1 level) using LPPS, SPPS, or hybrid synthesis for oligonucleotides at our facilities in Croatia and Israel, with reactors ranging from <100L up to 2,000L. 
• Fermentation: Our Hungarian site specializes in high-capacity fermentation, achieving production levels above 400MT/y with reactors from 150L up to 115,000L. 
• High Potent APIs (OHC≥6): For payloads and linkers used in ADCs, our sites in Italy, the Czech Republic, and Israel offer capabilities with reactor sizes from <100L up to 7,000L. 
• Steroids: Leveraging over 40 years of expertise in steroid synthesis, our Italian facility operates reactors ranging from <100L to 7,000L. 
• Small Molecules (incl. OHC 4): Across our global network, we manufacture deuterated compounds, metal organic complexes, and inorganic products with reactor capacities from <100L up to 17,000L. 

These site-specific proficiencies, combined with our commitment to GMP and regulatory excellence, ensure that TAPI can deliver tailored, cost-effective solutions while maintaining the highest standards of quality and compliance. 

Optimizing Costs  

In an increasingly competitive market, controlling costs while maintaining quality is critical. TAPI’s global approach offers several key advantages: 

• Cost Efficiency: By leveraging local manufacturing strengths in different regions, we optimize production costs without compromising quality. This flexibility allows us to offer competitive pricing and efficient service tailored to your budget. 
• Scalability: With a network that spans multiple continents, we can easily scale up production as your business grows, providing the reliability and agility needed in today’s fast-paced market. 

Tailored Solutions for Your Geographic Needs 

Every customer has unique requirements, and at TAPI, we pride ourselves on offering flexible, location-based solutions. Our global network means that we can design and propose manufacturing strategies that best suit your specific operational and market needs: 

• Customized Proposals: Whether you are looking to optimize logistics, minimize costs, or align production closer to your key markets, our experts develop tailored proposals that take full advantage of our global footprint. 
• Regional Advantages: By understanding the regulatory landscapes and market dynamics in various regions, we help you navigate local challenges and leverage regional strengths. 
• Comprehensive CDMO Services: From early starting materials and intermediates to final product manufacturing, TAPI’s comprehensive services ensure that every step of your supply chain is optimized for efficiency and reliability. 

Uncompromising Commitment to Quality and Compliance 

Quality is non-negotiable in pharmaceutical manufacturing. At TAPI, we operate with an unwavering commitment to high compliance and regulatory excellence: 

• GMP-Grade Manufacturing: All our facilities are built to meet stringent GMP standards, ensuring that your products are manufactured to the highest quality benchmarks. 
• Robust RSM Capabilities: With specialized expertise in Regulatory Starting Materials (RSMs), our sites are equipped to support the entire production lifecycle—from initial development to full-scale commercialization. 
• Quality-First Culture: Our teams continuously invest in training and technology to maintain a culture of excellence and ensure that every project is delivered with the utmost precision and care. 

A Partner You Can Trust for Global CDMO Services 

As we move further into 2025, the demands on pharmaceutical manufacturers are greater than ever. TAPI’s global manufacturing network, cutting-edge technology, and dedicated teams are here to support you at every stage of development and production. Whether you require multiple sourcing options, customized proposals based on your location, or advanced manufacturing capabilities, TAPI stands ready to be your trusted partner. 

Our expansive global footprint not only enhances supply chain continuity and security—it also provides the flexibility and innovation needed to bring your therapies to market quickly and efficiently. We invite you to explore how TAPI’s CDMO services can help you achieve your manufacturing goals and drive success in an increasingly competitive landscape. 

At TAPI, we believe that a global approach leads to local success. Let us show you the power of a diversified, expert-driven manufacturing network tailored to meet your needs—no matter where you are in the world.

Contact us today to learn more about our global manufacturing solutions and how we can support your project from concept to commercialization. 

At TAPI, our Contract Development and Manufacturing Organization (CDMO) capabilities are designed to address the complex challenges of developing oligonucleotide APIs. These advanced modalities require specialized expertise to ensure quality, regulatory compliance, and process efficiency from early-stage development to full-scale production. Our proven track record in overcoming technical challenges enables us to provide high-quality, flexible solutions tailored to our customers’ needs. 

A prime example of our expertise in action is our work on Nusinersen, a complex oligonucleotide API. Our recent discussions at TIDES Europe highlighted the intricate challenges of achieving regulatory compliance while maintaining the highest standards of quality and efficiency.

Expertise in Oligonucleotide Development: The Nusinersen Case Study 

TAPI’s experience in oligonucleotide development was demonstrated at TIDES Europe, where our R&D team presented critical insights: 

• Michael Tikhonov, R&D Analytical Group Manager, discussed the analytical challenges of developing generic oligonucleotides, particularly in impurity profiling. 
• Daniel Pinchuk, Group Leader Chemical R&D, gave an in-depth presentation on the development of Nusinersen API, emphasizing how TAPI ensures quality and regulatory sameness with the Reference Listed Drug (RLD). 

Daniel and Michael’s talk explored key factors such as phosphorothioates diastereomeric composition, and cost considerations, while also showcasing the advanced statistical tools TAPI employs to ensure similarity. 

Watch the Full Presentation: here 

Challenges of Generic Oligonucleotide Drug Substance Development

Developing a generic version of Nusinersen presents unique challenges due to its complex structure. In 2022, the FDA issued product-specific guidance recommending that generic versions establish diastereomeric composition sameness with the RLD. This is no small feat—Nusinersen is a mixture of approximately 130,000 stereoisomers! 

At TAPI, we take a rigorous approach to ensuring quality and sameness, from manufacturing process development to analytical characterization. Our methodologies focus on key parameters that influence the final diastereomeric ratio, ensuring regulatory compliance while maintaining high-quality standards. 

FDA Recommendations for Diastereomeric API Sameness 

The FDA guidance outlines several key recommendations for achieving sameness:  

• Selecting and controlling reagents and reaction conditions carefully  
• Measuring the R/S ratio at each elongation cycle using appropriate methods  
• Comparing the diastereomeric composition of the generic API to the RLD 

TAPI’s Approach 

At TAPI, we leverage advanced analytical techniques to ensure diastereomeric consistency in our generic Nusinersen API. Our approach includes: 

✔️ Evaluating the R/S ratio at each elongation step using LC-MS 

✔️ Carefully selecting fractions during purification to optimize the diastereomeric ratio and impurity profile 

✔️ Using ³¹P NMR fingerprinting, combined with PCA, correlation algorithms, and R/S ratio analysis, to demonstrate diastereomeric sameness 

By combining cutting-edge analytical tools with our expertise in complex API development, we ensure that our generic oligonucleotide APIs meet the highest standards of quality and regulatory expectations. 

CDMO Capabilities in Action: What This Means for Our Partners 

The challenges of developing Nusinersen illustrate the depth of TAPI’s CDMO expertise and our ability to tackle complex problems to deliver high-quality solutions for our selected partners. Our expertise will be at your disposal to: 

• Overcome complexity: Navigating the challenges of large stereoisomeric mixtures and ensuring regulatory compliance. 
• Innovate solutions: Implementing analytical and manufacturing techniques that enhance process control and optimize outcomes. 
• Ensure regulatory success: Adhering to FDA and EMA guidelines to guarantee product safety and efficacy. 
• Control isomer ratios and process stability: Managing chiral purity through purification, scale-up, and stringent process monitoring. 
• Optimize manufacturing from development to commercial production: Understanding process parameters that influence quality, ensuring smooth scalability, and implementing state of the art equipment. 
• Improve efficiency and quality: Process Analytical Technology (PAT) is implemented. PAT enables real-time, quality-based adjustments to the process. 

By leveraging these capabilities, we provide our partners with confidence in their oligonucleotide projects, ensuring a seamless path from development to commercialization. 

Customized CDMO Solutions at TAPI 

At TAPI, we offer tailored CDMO solutions for every stage of your API journey. With over 85 years of API development and manufacturing expertise, we provide flexibility and innovation to meet your unique needs. Our global presence, advanced technologies, and unwavering commitment to quality and compliance enable us to deliver solutions across a wide range of modalities. 

Our extensive experience spans advanced oligonucleotide modalities such as Antisense Oligonucleotides (ASO), small interfering RNA (siRNA), and Conjugated-Oligonucleotides. This breadth of expertise further reinforces our position as a leader in the oligo CDMO space, ensuring that we meet the evolving needs of our partners. 

Whether your project involves peptides, oligonucleotides, fermentation products, steroids, or small molecules, we are equipped to support you every step of the way. 

• Peptides & Oligonucleotides: Tailored manufacturing from research to commercial production, with reactor sizes ranging from 100 L to 2,000 L for peptides. 
• Wide Range of Capabilities: Offering regulatory starting materials, intermediates, and APIs for a diverse set of products. 

Whatever your project needs, TAPI is ready to deliver.