This article was originally published on 4.7.2022. Since then, Teva has continued its push towards achieving its yearly ESG targets – including donating 30.4 million doses of essential medicines to Ukrainian citizens in need, achieving a 41% increase in total proportion of electricity purchased or generated from renewable sources, and $44B in savings from generic medicines across 21 countries in 2022.

Read more insights from Teva’s 2022 ESG Progress Report here. 

ESG in Pharma – Why it Matters

In this podcast episode, we discuss environmental, social and governance (ESG) issues in pharma with Teva Pharmaceuticals experts, Itamar Schwartz and Adam Ajzensztejn. We deep-dive into why ESG is such a buzz word at the moment, what impact the pharma industry can actually have, and what makes Teva’s recent $5 billion sustainability-linked bond the first of its kind. Listen now!

Or find us on your favorite podcast app!

Here’s an overview of what we covered in our discussion:

A bit of background

The topic of ESG has catapulted into the limelight recently. Not just in the pharma industry but everywhere.

Investors, employees, customers, consumers and regulators all are demanding firms be more transparent about their plans for tackling environmental, social and governance issues from global warming and pollution to discrimination and forced labor. The risks for companies that are seen as moving too slowly are high.

What exactly is it that makes it such an important topic? And for the pharma industry, and specifically for Teva – what are we doing to make strides in terms of our environmental, social and governance elements? What actions are we taking and what impact will they have when we are successful?

The topic of ESG has evolved over many, many years. What started off with the concept known as corporate responsibility in the 70s has now morphed into what we call ESG.

In the early days, one of the main goals of any company was to bring profit to shareholders, so implementing corporate responsibility factors was very important in order to get the shareholders’ buy in into the company’s vision. So, companies use to make charitable donations and employees had to spend time volunteering.

Now, with ESG we’re talking about value rather than just profit. More than succeeding in giving profit to shareholders, we need to be giving value to stakeholders – when we say stakeholders, we mean investors, suppliers, customers, regulators.

We have to look at it from the scope of risks and opportunities associated with company’s non-financial performance. So it involves everything from data privacy to employee wellbeing, from fair pricing to a sustainable supply chain.

Why ESG is so important

It is important simply because of data. Investors coined this term so companies would set metrics for each component of E, S, and G. it can then be measured, so that the value that companies claim they create can be measured and compared to their industry peers.

It’s the same as financial data. The new consensus among investors is that the non-financial is the new financial. If you want to really evaluate a company you have to look at the non-financial data.

Many studies have already shown that ESG really makes an impact in the long-term. It’s no longer a question about whether it makes an impact. It’s about how you can measure it, and seeing how we can have global unified standards to measure all companies using the same metrics.

Teva’s $5 billion sustainability-linked bond

Teva recently issued a 5 billion dollar sustainability-linked bond. This was the largest ever, the first in the generics industry, and the first in the pharma sector with E and S targets.

It’s a type of bond where the bond itself is tied to sustainability targets. If the company does not achieve the target, they have to pay a penalty to bond holders.

2021 was the year of long-term goal setting for Teva, to make sure they were on track to meet and create sustainable value for the long term. It was clear that some of these goals should be tied to the bond as evidence of an increased level of commitment that the company has to ESG.

The vision was very clear — to make ESG everyone’s business at Teva. A sustainability-linked bond is how they set about to achieve this vision.

The climate crisis – Teva’s goals

The targets they set themselves are ambitious. To reduce greenhouse gas emissions by 25% by 2025 and then to further that reduction to 46% by 2030.

These are quite challenging targets – to reduce emissions by almost half in about a decade. To do that, we need to make fundamental changes to the organization.

A structured coordinated set of systems and processes need to be implemented to achieve these targets. To do that, a sustainability task force was set up within Teva, of different disciplines aiming to execute on the strategy of decarbonization. Each person is coming with their own experience and point of view to help decarbonize Teva from within.

The bulk of the Teva footprint is sitting in their value chain — upstream and downstream. It accounts for 90% of total emissions. For example, raw materials used require energy as part of their production and this will emit greenhouse gas emissions.

Likewise, on their other side of their operations, the use of products and throwing them away at the end of life, requires their disposal and that also results in emissions.

Because Teva doesn’t have direct control on the value chain, it’s a tricky thing to try to reduce. But they set a target anyway because they understood how valuable it is. The target is to reduce emissions by 25% by 2030.

A large part of these actions is engagement with the supply chain on ESG topics and specifically climate change and greenhouse gas emissions. They identify those critical suppliers first to work with them and lean on them to reduce their emissions.

It’s like a domino effect with everyone in the chain leaning on the next one down the line.

Access to healthcare – Teva’s goals

Being one of the largest generic manufacturers in the world, Teva really has unique possibility of really impacting access on a global scale. They make access possible, and a lot more affordable.

90% of children with cancer in sub-Saharan Africa do not survive. In the developed world, 80% of children survive. The children in sub-Saharan Africa simply cannot access the medicines that are needed.

Barriers include corrupt governments, governments without resources, operational barriers such as lack of doctors, lack of hospitals and lack of pharmacists.

To tackle these access barriers, Teva has developed a program called Global Hope, in partnership with Direct Relief and Texas Children’s’ hospital, where Teva donates medicines to help these children.

The World Health Organization has an essential medicines list. For cancer treatment, Teva has 73% of treatments on the list. So they can really bring a lot of value in this field.

Teva has committed to two access targets. The first is to increase new regulatory submissions by 150% by 2025, and the second is to increase the product volume, that is either donated or through a social business initiative, by 150% — so more medicines to more patients in need.

Measuring ESG efforts

All of the targets can be measured and Teva has committed to report on progress in their annual ESG progress reports.

In terms of environmental data, hard data is collected from the sites on so many different indicators. It’s then analyzed and the team sees how it transforms over time, and the different trends.

For example, with greenhouse gas emissions, Teva needs to understand their energy consumption and how the emission factors apply to different types of energy in different countries. They look at vehicles and where the emissions from those are coming from.

A big accounting exercise is done, according to international protocols. This is then externally assured as well to make sure Teva is following the rules, and to make sure the data is credible and robust.

This data is taken and scored by external bodies. As of the end of 2021, Teva was in the top 20% in five of the ratings. This includes the EcoVadis rating, which is interesting because it comes from customers rather than investors and assesses ESG performance all around the value chain. Teva managed to improve their score from 56 to 63 in one year and receive the EcoVadis silver medal. In fact, they’re in the top 12% of pharmaceutical companies.

Listen to the podcast here or contact us for more information.

This is the third episode in Teva api’s podcast, “The World of the API,” where we explore the stories of the work we do at Teva api, through conversations with the scientists, leaders and experts who make it happen. The podcast is available on all streaming channels.

Check out our latest podcast, Respiratory APIs: a peek into the lab with our experts, where we deep-dive into the challenges of respiratory APIs. We join Dr Ales Gavenda, Director of R&D in Czech Republic and Italy, and Oshrat Frankel, our Head of New Technologies, Innovation and Pre-formulation, for a guided tour.

Or find us on your favorite podcast app!

If you prefer the written word to the spoken word, here’s an outline of the podcast.

The Market for Respiratory APIs

The chemical, physical and bulk properties of APIs for respiratory formulations are especially important and dramatically influence on the behavior of the API during the formulation process, and more importantly the performance of the drug product during treatment.

Over the last few decades, there has been a huge growth in the number of non-cancer respiratory diseases. Asthma medication for example is projected to rise from 10% of the respiratory market in 2019 to 23% by 2024, while other Asthma or allergy related medication will rise from 21% to 26% during the same time period. According to GINA, it is estimated that – asthma affects ~350 million people worldwide, 25MM+ in the US alone, including 6MM children. On top of that, COPD is estimated to impact 310MM people in the world, with 13MM in the US diagnosed, and 24MM with impaired lung function.

At Teva api, the R&D team is deeply engaged in developing a variety of respiratory APIs. This includes thinking about formulation, suitability to the relevant devices, stability and much more. It all starts with R&D.

Unique Challenges of Respiratory APIs

Respiratory drugs present a unique set of challenges, because most of them are delivered through inhalation as powders. That means that the API has to be broken down into fine particles through a process called “micronization”. Once developers have created a suitable powder, the next issue is finding the right delivery device to get it into the lungs.

Oshrat explained to us how crucial it is to choose the right delivery device. There are a few types of devices:

1. Dry powder inhaler (DPIs) that contain a powder made up of the API and a carrier, usually lactose particles, which gets the medicine into your lungs. The patients inhales a really big breath in, so that the full dose gets to their lungs. This can be challenging for many patients.
2. Metered dose inhalers (MDIs). a blast of medicine is delivered by pressing a button. They are aerosol powered and deliver a fixed dose using an HFA, or hydrofluoroalkane, propellant. They are very accurate as they deliver the same dose every time.
3. Soft mist inhalers which create a cloud of medicine that can be inhaled without the help of a propellant or lactose.

While in regular medicine the API doses might range from several milligrams to around one gram, in the respiratory APIs administered by inhalation, doses are tiny, usually only a few micrograms – which is hundreds of thousands, if not up to a million times smaller than a regular API dose. That is a challenge for many of the API companies. These highly APIs allow a much smaller margin of error when developing products for specific inhalation devices. We, at Teva api, have a range of techniques to do full physical characterization and beat this challenge.

Understanding Particles for Respiratory APIs

One of the most important things to think about for respiratory APIs is the shape of the particle. Obviously, API particle shape and size will impact particle surface area. This is called, Morphology.

For example, some particle shapes, like needle shapes, don’t stick very well to the carrier used in the dry powder inhalers. That means they often don’t reach the right part of the lungs. The more suitable shape for respiratory API is a round shape or regular shape particles which has optimized aerodynamic properties, so we can expect they reach the right place in the lungs.

Another thing to consider is particle size. The idea is to create just the right size of particle to reach the right place in lungs and be deposited there effectively. So for DPI formulation, for example, particles with a mass median aerodynamic diameter of below 10 micrometers are ideal.

Those particles reach the right part of the lungs, through the bronchial tree and alveolar regions, and are deposited there. Any larger, and the particles end up stuck in the airways or mouth, or even swallowed. Any smaller and they tend to be exhaled before they’re deposited, which means that they don’t have a chance to work.

In the end, the majority of all respiratory particles of API are lost this way. Of course these variables cannot be eliminated, and they need to be considered when developing the API drug substance.

Other important Factors in the Respiratory API Process

But it’s not only the shape and size of particles that matters. All sorts of other factors need to be examined during the development process. For example, most drugs come in a crystalline form, and could potentially exist in many forms. These are known as “polymorphic forms” and there can be huge differences between them, which have significant implications for pharmaceutical applications — everything from physical properties, product stability, solubility to formulation aspects.

This has a huge effect on how the drug works — how effective it is, e.g. bioavailability. It’s also important to look for amorphous traces, which are traces of non-crystalline material with potential impact on API solubility and stability. Obviously amorphous content needs to be controlled.

At Teva api, we quantify it via various analytical instrumentation e.g. thermal techniques like modulated differential scanning calorimetry, microcalorimetry and others to measure amorphous content in our products. However even more important is to set micronization parameters in order to minimize amorphous matter creation.

In addition, we have developed specific processes how to remove amorphous matter from the final product. This is a unique know-how which makes our final API much stable in terms of physical properties during manufacturing and its storage.

Micronization

To ensure the right particle size, the API goes through a process of micronization, which means breaking down bigger crystals into a fine powder.

At Teva api, our scientists and engineers are always working to optimize our particle size reduction techniques. Because we perform this development internally, it gives us better control over the process, and also greater flexibility. Really it’s about being able to tailor solutions to each customer’s exact needs.

The first point for perfect micronized product is consistent crystalline API input for milling or micronization. For that we optimize crystallization in all aspects in order to have robust crystallization process and consistent particle size and morphology.

Our Center of Expertise in Europe has various technologies for size reduction available in one place. Among our technologies are various types of milling and micronization with QbD approach. Our experienced experts are exploring all possibilities to find the right technology and equipment for our products. When we find the optimal technology and conditions, we perform technology transfer to production site and verify again the final product quality.

Since particle size is so -important for respiratory drug product, we can provide tailor-made particles for each customer‘s formulation development. We can provide several grades of particle size for testing the right target during pharmaceutical development. Once the right particle size is found adequate for formulation, we continue to work on monitoring other physical properties.

Flowability

Flowability means whether particles flow freely over each other. This is tested by a special machine called a powder rheometer. By measuring the powder’s resistance to the probe, you can see whether the API flows well and is suitable for formulation, or tends to stick together, which can cause some trouble during formulation and storage. Examining bulk and tap density is also crucial and may impact how the powder will behave during processing and storage.

All the research coming out the industry confirms how important all of these processes are in developing respiratory APIs. For more information, make sure to check out the full podcast right here!

Respiratory APIs & The Teva api Advantage

Teva api has a variety of respiratory APIs and our R&D team is invested in developing an in-depth understanding of the formulated API. We look at everything from manufacturability and stability to legal issues, and factors that could affect formulation development. We offer a complete support package on the sales side of things, but that obviously has to begin with research and development.

We have approximately 15 different respiratory APIs across all therapeutic categories, making us a leading supplier in this sector. The respiratory segment is a hugely important one right now. So we’re really going the extra mile.

All our respiratory APIs are produced in state-of-the-art facilities both in R&D and in production. We can work with highly potent APIs, including steroids. We have the personnel, the expertise, the equipment, and decades of scientific experience. Tools such as Design of Experiments methodology, computational tools, modelling, and Process Analytical Technology help the team design, analyze, and tightly control manufacturing processes. And this ensures the highest quality products.

Our respiratory portfolio has been the largest in the industry for some time, and we’ve just added four newest products for pharma R&D development. You can reach out to us to learn more on those products.

This is the second episode in our podcast series, The World of the APIs, where we speak to the scientists and experts who make the APIs happen.

Why lumping and flowability are an industry pain that is difficult to resolve… and why Teva api is determined to do something about it

Active Pharmaceutical Ingredients have several important physical powder properties including hygroscopicity, compactability, flowability and lumping.

Powders are complex materials… they could even be accused of having personalities…

• Not flowing
• Sticky
• Not loose
• Sensitive
• (Flowing) Not spontaneously

See how Teva api’s R&D experts can help you with flowability and lumping.

Several pharmaceutical processes including storage of powder, transportation, blending and compaction are influenced by powder behavior. Powder behavior issues such as flowability and lumping have been major challenges for the pharmaceutical industry, which works mainly with powders. These phenomena are complex, poorly understood and handled, and require prior experience and advanced analytical tools in order to be understood and resolved.

Flowability in Active Pharmaceutical Ingredients

Flowability – is the ability of powder to move in a specific system. The powders are lined up from “free flowing” powder to “non-flowing” powder.

Flowability of a powder refers to the specific relevant system. The same powder can flow with no issues in one system but will face difficulties in a different pharma equipment.

Flowability is a complex factor influenced by multi physical properties. Therefore the key to improve flowability will rarely be a small change in one production parameter and will not be characterized by a single analytical test.

Combinations of analytical tests (such as: angle of repose, compressibility index and Hausner ratio, flow through an orifice, shear cell methods) and deep evaluation of:

• Material features (electrostatic charge, cohesion and hygroscopicity)
• Production parameters (drying, milling processes)
• Environment conditions (humidity, moisture content and storage container)
• Pharma equipment that the powder should flow through

Will provide that starting point for improving the way the powder moves in pharma equipment.

The analytical tool can be useful in order to evaluate “better flowing” material, can distinguish between batches and allow you to have fine-tuning on your production parameters in order to comply with pharma requests and formulation instrumentation.

Lumping in Active Pharmaceutical Ingredients

Lumping can occur during storage: small aggregates accumulating over time within the powder, in extreme cases the entire powder takes on the shape of the container.

Lumping can also occur during drying: during solvent removal, lumps requiring “pre-milling” are created and in some specific cases, the lumps are too large to be milled by conventional means.

Lumps formation in the API is studied already in the early R&D stage. Several aspects of the Active Pharmaceutical Ingredient are considered in order to predict lumps formation: solubility, hygroscopicity, package information, particle size (milled, micronized) and solvents used in the last process step. Using multiple analytical tools such as microscopy, contact angle, PSD, lumping prediction in small scale, surface area, bulk and tapped density, angle of repose and more, Teva api is able to predict and control lumping in our APIs.

Lumping can be characterized by many analytical tools such as: microscopy and surface area (SSA)

Solving lumping issues, a case study

Tackles lumping is an Active Pharmaceutical Ingredient that has been produced by Teva api for more than 20 years and was known as lumped material. The solution to this lumping came from our customer’s formulation equipment that had separated all the lumps. A request from another customer raised the need of Teva api to evaluate the root cause and find a lasting solution to the phenomenon. One known technique to prevent lumps forming is to change the drying procedure. In this particular case, being the material highly hygroscopic, it was discovered that the discharge of the material from the drier needs to happen at a temperature very close to room temperature to prevent water absorption during cooling which could bring to the formation of water bridges.

After taking this precaution the lumping formation was reduced, but still some small lumps were observed in the material.

Further analyses led us to discover that residual solvent from the crystallization process can also contribute to the creation of lumps.

Residual solvent that was trapped in the wet part of the powder (part of the powder that was not well stirred or left in the corners of the dryer) was contributing to these smaller lumps. So additional drying was needed for that layer.

Another way to prevent lumping involves the packaging of the powders, this solution is recommended in cases of soluble material in water or in organic solvent.

All grades of particle size of this material had a tendency to lump over time. Extended drying and cooling prior to unloading solved the issue for the large and medium grades.

The fine grade material (micronized grade) would often lump even at the end of milling. Along with extended drying and cold unloading, packaging with N₂ has prevented lumping for at least 6 months after packing.

This complex problem is a challenge we accept on behalf of our customers

With our years of experience in the improvement of powder flowability and the prevention of lumping, Teva api is the industry leader. Teva api is constantly looking at new techniques, procedures and products that improve our customer’s end product experiences and their satisfaction with our Active Pharmaceutical Ingredients. By working in close cooperation with our customers we are ensuring that the properties of our powders match our customer’s expectation.

What is downstream processing (DSP) expertise?

Teva api’s downstream processing (DSP)

Teva api downstream processing (DSP) capabilities cover a broad range of products: from antibiotics, statins and immunosuppressant’s to high-potency compounds and enzymes. Our cutting-edge technologies, deep process understanding, and exceptional R&D services meet the most demanding industry standards.

Teva api owns large and modern downstream processing plants harmonized with our fermentation plants. They are highly automated and operated by skilled and experienced professionals who specialize in performing recovery processes required after fermentation.

Our R&D experts are involved in all stages of the product lifecycle to continually improve productivity and product quality for both new compounds and existing products.

Downstream Processing Activities

Our downstream processing activities cover diverse operations including whole broth extraction, vacuum-drum filtration, membrane filtration, evaporation, thin film evaporation, silica gel chromatography, ion-exchange chromatography, adsorption resin chromatography, crystallization, filtration, and drying. A DSP pilot plant and a DSP mini plant advance technology by delivering and implementing new processes across the facility.

Over the years, the Teva api downstream processing (DSP) team has conducted several technology transfer projects that have strengthened our QA, regulatory and other industry-leading competencies. Our R&D, engineering and production teams collaborate closely to ensure we consistently operate efficiently and effectively.

Teva api products, which involve the use of downstream processing expertise, are varied and include API products such as: Mitomycin, Tacrolimus, Caspofungin and more.

A discussion with Teva experts on why ESG makes a difference

The World of the API is a podcast series by Teva api. In this series, we explore the stories of the work we do at Teva api, through conversations with the scientists, leaders and experts who make it happen.

In episode #3, we have a chat with Teva Environmental, Social, Governance (ESG) experts, Itamar Schwartz and Adam Ajzensztejn about ESG in pharma. We talk about why ESG is such a buzz word at the moment, what impact the pharma industry can actually have, and what makes Teva’s recent $5 billion sustainability-linked bond the first of its kind.

Discover the podcast on

Watch this space for more episodes of the The World of the API podcast.