Sustainability in the pharmaceutical industry is not only about setting ambitious goals. It is about embedding responsible practices into the everyday environments where science happens.

At TAPI, this includes the laboratories where our teams develop, improve, and support complex API and CDMO solutions. As part of our commitment to responsible innovation and continuous improvement, TAPI is advancing sustainable laboratory practices through My Green Lab® Certification.

What is My Green Lab® Certification?

My Green Lab® Certification is an independent, third-party verified program that assesses laboratories across 14 sustainability categories, including energy, water, waste, chemicals, procurement, and culture.

The certification program is widely recognized as a leading standard for sustainable laboratory operations and is used by many of the world’s top pharmaceutical and biotechnology companies. Laboratories are assessed and awarded certification levels based on their performance, from Bronze to Silver, Gold, Platinum, and Green.

Achieving certification reflects a laboratory’s commitment to reducing environmental impact while supporting safer, more efficient, and more responsible operations.

For TAPI, this recognition is more than a certificate. It reflects our commitment to responsible science, operational excellence, and sustainable progress across our global network.

Why Sustainable Laboratories Matter

Laboratories are essential to scientific progress, but they can also be resource-intensive environments. By adopting more sustainable practices, labs can reduce energy consumption, improve waste and chemical management, conserve water, and strengthen awareness around responsible daily operations.

These improvements support both environmental performance and operational quality. More efficient use of resources, better inventory control, responsible chemical handling, and stronger lab engagement contribute to safer, more reliable, and more controlled R&D environments.

For our partners, this provides additional confidence that TAPI is working to align scientific excellence with responsible operations and evolving ESG expectations.

Building a Culture of Sustainable Science

Sustainable laboratory practices require more than process changes. They depend on awareness, engagement, and consistent action from the people working in the lab every day.

Through My Green Lab® Certification, our teams are encouraged to assess current practices, identify opportunities for improvement, and embed sustainability into daily routines. This includes actions such as switching off idle equipment, optimizing energy use, reducing waste, improving chemical inventory management, and encouraging greener procurement decisions.

These efforts reflect TAPI’s broader commitment to doing the right thing for our customers, our communities, and the planet.

Recognized TAPI Labs

As part of this ongoing journey, TAPI is proud to recognize the laboratories across our network that have achieved My Green Lab® recognition. Each lab’s progress reflects local ownership, strong engagement, and a shared commitment to advancing sustainable science.

TAPI Rho Chemical R&D Lab Achieves My Green Lab® Platinum Certification

TAPI’s Rho Chemical R&D Lab has achieved My Green Lab® Platinum Certification, in recognition of their sustainability efforts.

The certification reflects a comprehensive effort by the Rho team to evaluate, improve, and embed sustainable practices across daily laboratory operations. Each requirement of the My Green Lab® program was analyzed and addressed, ensuring that the necessary actions and policies were in place.
Key focus areas included energy efficiency, waste and chemical reduction, greener laboratory operations, and employee engagement.

The lab implemented energy-saving practices such as switching off idle fume hoods and instruments, optimizing ventilation and cold storage settings, and encouraging more energy-conscious daily routines.
The team also improved waste management practices by expanding recycling efforts and reducing hazardous and chemical waste where possible. Better inventory control, greener experiment planning, and efforts to minimize expired chemical disposal helped support more responsible use of laboratory materials.

In addition, the lab integrated green chemistry principles and sustainable procurement practices into R&D operations. This included efforts to substitute or reduce hazardous reagents when possible, purchase more sustainable lab consumables, and conserve water through practical improvements such as recirculating cooling systems and leak prevention.

A dedicated Green Lab team at Rho guided these efforts, with strong leadership support and broad lab engagement. Employees participated in training, surveys, idea generation, and daily sustainability actions, helping create a culture of continuous improvement.

Achieving Platinum Certification provides independent validation of the Rho Chemical R&D Lab’s environmental performance and reinforces TAPI’s commitment to responsible innovation, safer operations, and sustainable progress.

TAPI Czech Republic R&D Receives My Green Lab® Platinum Recognition

TAPI is also proud to recognize TAPI CZ R&D for receiving My Green Lab® Platinum recognition.
This achievement reflects the team’s commitment to embedding sustainable practices into daily laboratory work and contributing to TAPI’s broader efforts to advance responsible science across our global R&D network.

By reaching Platinum level, TAPI CZ R&D demonstrates strong performance in sustainable laboratory practices and reinforces the importance of local engagement, continuous improvement, and operational responsibility.

Together with the Rho Chemical R&D Lab, this recognition marks another important step in TAPI’s journey to expand sustainable laboratory practices across our sites.

Continuing Our Green Lab Journey

The recognition of these labs is part of an ongoing effort to strengthen sustainability across TAPI’s laboratory network. As more labs advance through the My Green Lab® Certification process, we will continue to share their progress, achievements, and practical actions.

Each recognition reflects the work of dedicated teams who are helping make sustainability part of everyday scientific practice.

Through these efforts, TAPI continues to advance responsible innovation, safer operations, and sustainable progress across our global network.

At TAPI, advancing health from the core means more than scientific excellence. It also means protecting people, preserving resources, and building a safer, more sustainable future across our global organization. 

That is the idea behind the first-ever TAPI EHS&S Awards 2025 — a new global initiative created to recognize exceptional contributions in Environment, Health, Safety and Sustainability across TAPI. 

Launched in mid-October 2025 and highlighted during TAPI EHS&S Week in November, the awards were created to celebrate individuals and teams whose work goes beyond compliance and creates real, lasting impact. Whether through innovation, leadership, collaboration, or continuous improvement, these are the people helping strengthen TAPI every day. 

The program also reflects TAPI’s principles in action: A community more than a company, We love to win, Beyond is where we begin, and We crave science and technology. 

Why These Awards Matter 

In their first year, the EHS&S Awards drew 43 applications from across TAPI in categories including Environment & Sustainability, Safety, Health, Culture, and Other. 

Each submission was reviewed by the Global EHS&S team based on clear criteria: 

• Innovation and originality 

• Magnitude of impact 

• Sustainability and long-term applicability 

• Measurable results and quality of data 

• Replicability across sites 

Following the review process and alignment with top management, four winning projects were selected and announced during the TAPI Q4 and FY2025 Town Hall on January 29, 2026. 

Together, the winners show what EHS&S excellence looks like at TAPI today: practical, people-centered, measurable, and forward-looking. 

Netanel Hakimi 

“Community more than company – doing it together” 

TAPI Israel, Abic 

As TAPI continued strengthening its independent EHS&S practices, the Abic site identified a need for a simple and effective way to report safety observations, hazards, and near misses in its dynamic R&D environment.

The answer was GOARC, a digital safety platform installed on employees’ phones, enabling real-time reporting and immediate follow-up. With strong training, communication, and leadership support, the tool quickly became part of daily work. 

Since launch on July 1, 2025, the site has recorded more than 100 hazard reports and over 50 observation reports, with a closure rate above 90%. Just as importantly, the initiative has helped strengthen trust, accountability, and collaboration across departments. 

This project stood out for turning safety reporting into a shared cultural practice — making prevention more visible, more accessible, and more effective. 

Engineering and Energy Utilities Team 

“Utilization of Waste Heat from WWTP Blowers” 

TAPI Czech Republic, Opava 

Pavel Stehlik’s team focused on finding a smarter use for energy already being generated on site. 

At the Opava wastewater treatment plant, heat produced during air compression for biological aeration was being wasted. The team identified an opportunity to capture that heat and redirect it to the neighboring main warehouse building. 

After system design, cost assessment, and equipment installation, the project delivered clear and measurable results. In its first year, it saved 714 GJ of heat and reduced natural gas consumption by 19,000 m³, generating approximately USD 17,400 in heating energy savings. 

The environmental impact was just as significant, with a reduction of 40 tons of CO2 emissions and additional savings linked to avoided emission allowance costs. 

This project is a strong example of how practical engineering can create value on multiple levels — reducing emissions, lowering costs, and improving energy efficiency at the same time. 

Anantha Rajmohan M 

“Smart Science for a Safer Tomorrow: AI and Automation Elevating EHSS Standards in Polymorph search ” 

TAPI India R&D, Greater Noida 

In TAPI’s polymorph search activities, Anantha Rajmohan M and the Greater Noida team rethought traditional workflows through the lens of EHS&S, combining AI, automation, advanced equipment, and improved engineering controls. 

Polymorph screening is strategically important, but it can also be resource-intensive. The team introduced a smarter model that reduced solvent handling, minimized exposure to hazardous chemicals, lowered waste generation, and improved ergonomics for scientists. 

Among the key improvements, solvent storage was significantly reduced, experiment scale was lowered, and advanced systems such as Genevac, Polar Bear, and high-throughput screening tools enabled more efficient, lower-waste experimentation. AI-driven calculation tools also helped reduce zero-yield experiments from 35–40% to around 10%, generating up to 25% savings in API use, solvent consumption, and man-hours. 

Beyond operational efficiency, the shift also reduced repetitive manual work and physical strain, allowing scientists to focus more on planning, analysis, and innovation. 

This project stood out for showing how science and technology can directly improve safety, sustainability, and research quality — all at the same time. 

Teva Tech Team 

“From Risk to Resilience – Setting a New Benchmark for Managing Acutely Toxic Chemicals” 

TAPI Israel, Teva Tech 

The Teva Tech Team project addressed a major safety challenge: managing acutely toxic non-API chemicals in the absence of formal best-practice standards. 

At Teva Tech, the team identified a gap in how substances with severe acute toxicity — such as Hydrazine Hydrate, DIC, and TBHP — were managed across their lifecycle. In response, they developed a comprehensive risk management strategy that created a new benchmark for safe handling. 

The project introduced improvements across storage, transport, transfer, sampling, emissions treatment, and disposal. These included minimizing packaging sizes, defining dedicated storage requirements, eliminating unnecessary sampling, implementing strict transportation guidelines, and establishing closed transfer systems with leak-tight engineering controls and early leak detection. 

The result was a significant reduction in exposure risk, improved industrial hygiene and process safety, and stronger control over hazardous emissions and waste. 

This project stood out because it did not simply improve an existing framework — it created one. It is a clear example of proactive safety leadership in action. 

Building a Stronger TAPI, Together 

The first TAPI EHS&S Awards highlight the depth of talent, commitment, and innovation across our global network. 

From strengthening reporting culture in Israel, to recovering energy in the Czech Republic, to transforming laboratory workflows in India, to setting new standards for chemical safety in Israel, each winning project reflects a different side of what responsible progress looks like at TAPI. 

Together, they show that EHS&S excellence is not only about reducing risk. It is about enabling innovation, supporting resilience, and reinforcing the culture that helps TAPI move forward — safely, responsibly, and sustainably. 

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. 

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. 

Last year, Teva api’s R&D leadership team got together to brainstorm about what could be done on a departmental level to make a substantial environmental impact. As a result of this meeting, a new “community” was formed called the R&D Green Community, and over the last year it has established many initiatives.  

The mission of the community is to identify and propose actions, technologies, and initiatives – within both the global and local sphere – aimed at reducing the environmental impact of activities performed in the Teva api R&D department. It also aims to promote a green culture within the department and create value out of green initiatives.  

Four distinct groups were created as part of the community, to tackle four different areas: 

      1.Energy  

The energy group aims to improve energy efficiency in the labs and pilot plants. It maps how the energy is being used and finds opportunities where the team can decrease energy consumption and where older technologies can be changed with newer, more modern technologies.  

For example, optimization of HVAC systems, conversion of Diesel based generators into dual mode with 70 % Piped Natural Gas and 30 % High Speed Diesel (HSD), reviewing the possibility of changing florescent lights to LED ones, replacing old refrigerators and freezers & replacement of R22 refrigerant, changing fume hoods that aren’t well-regulated, and working out how to utilize excess energy elsewhere.  

        2.Technology 

The technology group evaluates existing technologies, and suggests new technologies, solvents and catalysts. Examples of this in action are the use of continuous manufacturing in chemical processes and the successful implementation at GMP scale.  

The group also looks at water usage in the department and evaluates how to minimize or replace water. Their work has led to the installation of a centrally cooled glycol circuit (-15 to -8°C) for cooling small laboratory equipment such as evaporator coolers and EasyMax’s reactors to replace use of water-cooled thermostats.  

The below image illustrates the benefit of applying a technology where the products are manufactured in a continuous manner without isolation, thus reducing the effluent load on environment. The upper image shows traditional round flasks producing high effluent load which causes environmental issues. The lower image shows a continuous tube where, without isolation and without creating an effluent burden on the environment, production can occur.   

        3. Metrics  

This group has developed a computational tool for sustainability evaluation. The tool quantitively assesses the greenness and sustainability of a chemical process and gives a sustainability score between 1 and 100. 

Below shows what the scores reflect. 

The score considers multiple elements, including PMI, solvent selection, energy consumption, toxicity of materials, safety, atom economy, and process risks. 

Its aim is to enable chemists to make greener choices and to design chemical processes with improved efficiency and a lower environmental impact.   

Here is an example of a sustainability score evaluation for the amide formation reaction: 

        4.Value and Proposition  

This group works on networking, sustainability initiatives, and finding collaborations in and out of the organization.  

One such initiative is the Greeny award, a new annual award that encourages sustainability in the research and development facilities of Teva api R&D. The award is given to those who minimize or eliminate the environmental impact of processes in the R&D department, while also promoting a culture of greenness. It’s a celebration of innovation and creativity. 

Well done Teva api R&D team on this meaningful initiative! We hope you continue to make a significant environmental impact going forward into 2024.  

 

Our commitment to making a positive impact is at the heart of everything we do. Producing quality active pharmaceutical ingredients (APIs) so that our customers can create high-quality medicines, depends on us operating responsibly, ethically, and transparently.

In light of the 2019 Environmental, Social and Governance (ESG) Progress Report released by Teva this last week, here’s an overview of the ESG journey Teva api has taken over the last 5 years.

Achievements we’re proud of

In the last 5 years, we’ve reduced our Total Recordable Incident Rate (TRIR) by 80%, our Process Safety Event Rate by 60%, and the number of significant spills by 75%. We’ve also increased the reporting of near-misses (of accidents) by over 500%, enabling us to properly investigate the potential causes of a serious accident. We had over 21,000 EHS&S observations each year for the past two years that either led to immediate corrections of minor risks or encouraged improved practices.

In terms of environmental impact, we’ve reduced our waste generation by over 50%, and by 10% (9,350 metric tons) since 2018. To fight water scarcity, we’re doing our best to reduce our water usage, with a reduction of 10% (215,560 cubic meters) since 2018.

Our investment

We’ve invested a significant portion of our capital expenditure – over 100 million dollars – to reduce the biggest risks. These include major fire protection improvements, and securing dedicated and protected storage for chemicals.

We’ve improved our engineering controls to reduce the risk of potent compound exposure for our employees. We’ve minimized our environmental footprint with wastewater treatment plant improvements, and we are optimizing our environmental control units to minimize emissions of volatile organic compounds in the atmosphere.

Improving processes

We’ve introduced many new processes, with incredible support from our site managers and operations leadership, who fully embraced our goals and our mindset. We ran a process safety management survey with all of our sites and published safe-handling guidelines for highly toxic hazardous materials. We also implemented process safety management standards across all of the sites and created a comprehensive training program for our employees.

Our motivation

The road to EHS&S excellence is long and sometimes bumpy, but what matters is to stay focused on our goals and vision to ‘Target Zero’, which means zero accidents, zero injuries, and zero releases (spills and accidental discharges).

I truly believe that each initiative and every process we’ve implemented is another step in helping us to reach that goal and we are aiming to become a reference for excellence in the pharma industry.

Social initiatives to reduce our environmental footprint

We’ve always got different projects going on within the different sites, and our teams are keen to get involved in social initiatives.

Just one example comes from our Gajraula site, where approximately 100 employees recently volunteered to help clean the Ganga river (India’s longest river). People in India regard this river as a goddess and believe that the water is holy. The Indian government is taking an active interest in cleaning the water, and various funds have been set up to support the cause.

The Teva api team collected about 2.0 metric tons of biodegradable and non-biodegradable waste from the river. The biodegradable waste was then buried to be used as compost, and the non-biodegradable waste was set aside to be recycled. It was a great day for a great cause.

To access the Teva 2019 Environmental, Social and Governance (ESG) Progress Report, click here

Any manufacturing process has inherent safety risks, so it is essential to identify and reduce potential hazards before production begins. At Teva api, we are always looking for ways to improve methods and ensure best practices, and that includes making our manufacturing plants even safer, to protect our employees and keep production on schedule.

Identifying, assessing, and characterizing intended and, more importantly, unintended chemical reactions are critical to ensure safe process scale-up and different unit operations. Two years ago Teva api R&D began developing an innovative method that would pinpoint risk factors early on – during the design process – so we could recommend preventive safety measures before production got underway. We call it Safety by Design (SbD) based on the methodology used for pharmaceutical Quality by Design principles, which use a scientific approach to control product quality and process robustness (FDA 2008, Guidance for Industry: Q8 (R2) Pharmaceutical Development). SbD follows a similar method, using computer-aided process design and simulation tools to integrate safety, quality and productivity throughout the product lifecycle.

While SbD is still in the early stages of implementation, results are promising in the pilot and production plants that are following this process. They are successfully using this comprehensive data to minimize hazards, control health and safety risks. Teva api’s commitment to target zero safety incidents with the implementation of this new model has distinct advantages for customers. In comparisons to API manufacturing facilitates without systematic safety procedures, SbD reduces development time, which helps make the process more efficient. It enables Teva api to continue producing the high quality products our customers expect and delivering them without interruption.

Simulations and modelling are the backbone of Safety by Design

Most organic API synthesis processes are exothermic, meaning they produce heat. During production, excess heat must be removed to prevent possible undesired scenarios. In addition to being a safety issue for workers, the facility and the environment, excess heat can produce impurities, which affect active pharmaceutical ingredient quality.

We use reaction calorimetry to measure the maximal temperature of synthetic reaction (MTSR) and differential and/or adiabatic calorimetry to measure the critical temperatures to find the temperature of decomposition. The measurement is rated on a scale with five (5) classifications (Francis Stoessel: Thermal Safety of Chemical Processes: Risk Assessment and Process Design, Wiley 2008.). For example, a Class 1 process is considered safe – a temperature increase would not be considered dangerous. Class 5 represents the highest level of risk. If a cooling failure occurred, the molecules could decompose causing a thermal explosion. In Class 5 scenarios, the process either needs to be redesigned during development to reduce the criticality level, or additional safety measures need to be implemented during production.

In creating Safety by Design, our goal was to take the traditional approach to the next level. We developed a more comprehensive method using process simulation tools and mathematical models to predict real case scenarios in production. We know that calorimetric measurement can also provide kinetic data, and when supported with other analytical tools it can be used to determine reaction rates and potential side or runaway reactions. Combining the heat and mass transfer, thermodynamics, and the kinetics of the reactions, models can determine whether a process will be safe or unsafe. We can then easily adapt the findings to the operating conditions and equipment in a particular plant in a specific country.

By developing sophisticated computer models with process simulators, we learned that in the early phase of process development, we could predict and prevent hazards, control risks and help optimize the overall process. A systematic approach helped us gain a better understanding of potential safety issues by considering the reactants used in the process, their physical and chemical properties, the process conditions, heat and gas evolution, the equipment used in the process during the development stage, and finally, scale-up to production.

Case studies: How SbD reduced risk in API production

In two early test cases, process evaluation and modeling validated the importance of identifying potential hazards and engineering solutions during lab development.

Removing thermal instability: After running a specific API product through a safety assessment, the adiabatic calorimeter results indicated that process criticality was Class 5 due to the decomposition of solvent, DMSO. Further simulations also predicted that the process criticality would reach the highest risk. Redesign of the process is performed using different solvents and SbD evaluations to make the process safer. When we substituted the solvent DMSO with DMAc, the heat and pressure generation from secondary reactions dropped significantly and lowered process criticality to a much safer Class 2. The recommended solvent change increased operation safety without impacting product quality.

Reducing reaction conditions: We experienced a similar outcome when we ran a specific API product, one step through the SbD process simulation. When the solvent DMSO was used in the reaction mixture, the models showed the rate of heat generation could quickly rise to unsafe levels, making the process potentially thermally unstable (Class 4-5). By replacing DMSO with DMF in the process simulation, the reaction mixture safely stabilized without any safety risk (Class 1) and avoiding production delay.

In both cases, comprehensive evaluation during process design provided a clearer understanding of the potential dangers and gave us the opportunity to develop much safer solutions. In production, the solvent changes were successful and much safer, without impacting product quality or cost.

Continuous improvement makes best practices even better

In order to help us bring to our customers the best quality product in the most cost-effective manner, Teva api continuously pursues better methods and more advanced technologies to stay ahead of the curve. Safety by Design is a different approach – it elevates process safety to the same level of importance as product quality and environmental impact. But most importantly, it provides a framework for saving lives, preventing injuries and producing safe, high quality APIs for the most efficient and timely product delivery for our customers worldwide.