The Teva API site in Santhià, Italy, embarked on an innovative project to use artificial intelligence (AI) and machine learning (ML) to revolutionize API production.

The aim was to optimize and standardize the production process to reduce variability, raw material usage, and energy consumption, while enhancing productivity and API purity. It also sought to minimize downtime by predicting equipment failures and enabling rapid response to alarms.

 

Background and challenge

 

In the API and pharmaceutical industry, data is generated and collected by different tools like MRP, Lims, DCS, planning software, analytical instruments, and so on. In most cases, the data is not easily accessible from a single source, has different formats and is hard to organize and connect to a single event.

To fully understand a specific process phase, we need to identify the equipment where it is performed, connect all the process data and trends, the in-process control analytical results, the trace of the raw material entered in the lot, the maintenance and calibration history for the equipment used, the quality attributes, the possible deviations occurred before, during and after, and the efficiency of the utilities during the execution.

It is always difficult to have the full picture of a process phase, and even harder to have it in real time.

 

The solution

 

For this reason, we have developed an automated tool (in Python) to be able to do these connections for us. This tool can recognize the lots and the process phase that we want to study or investigate, can retrieve all the data necessary from different systems, recognize and extract the data of the same phase for other lots produced in the past.

The multi batch data (training set) are cleaned and aligned, then stored in a 3D matrix, where the three dimensions represent the batch number, variables and time. The data is analyzed with PCA and PLS methods, in order to understand the correlations between variables and reduce the dimensionality of the system.

At this stage in time, we are ready to prepare a model that can explain most of the variability between batches (yield, quality attributes etc.) with few variables (typically 2-3 dimensional models can explain 70-90% of the variability).

The model is then validated by testing the predictability on some lots that were not included in the training set (test set). The lots belonging to the test set can set and, at each cycle, the machine can learn something new.

 

Practical uses

 

How to use this model is up to you. It can be applied to different environments, including:

• Reproducing golden batches, understanding the reason why they were ‘different’ from the others or avoid reproducing ‘inadequate’ batches.
• Reducing the areas of the process to study in the lab, concentrating on the phases which are more connected with the variability of the result.
• Recognizing trends to understand if any equipment is getting close to a failure, improving safety and reducing downtime.

The improvement of process performance, sustainability and safety using AI and Machine Learning in the API and pharmaceutical industries is innovative, flexible and can be applied in different contexts, such as IT, Engineering, Quality, EHS, Operations, and R&D.

 

Real life examples

 

1. Alert generation from asset sensors

40 AI algorithms were developed to continuously monitor utilities and facility areas data. The algorithms can recognize patterns and trends that can potentially generate future alarms. The system generates immediate automatic alerts (emails, reports, potential route cause etc.) enabling the prompt check or corrective action by personnel.

This tool significantly reduced the time to resolution (in most cases avoiding alarm generation).  The increased monitoring of the asset, in the long term, also reduced the number of events.

 

2. Reproduce best repeatable batches (Yield)

 Process parameters from 31 batches (training set) were automatically collected. Each one of the batches originated approximately 10.000 variables (process, analytical, utilities etc.).  Using PCA and PLS tools, the dimensional space was reduced to 2 principal components. The 2 components model was able to justify 70% of process yield variability. This dimensional reduction allowed to simplify the batches comparison and clearly identify the most relevant parameters for the yield optimization.

The predictive model was successfully validated on 2 new batches. Consequently, the test data set has been added to the training set in order to improve model predictive performance for next iterations.

This successful project demonstrates how it is possible to benefit from the utilization of data, which is often collected but rarely fully exploited. We believe that this is just the beginning of a long journey into modernization that creates opportunities for both short and long-term usage and production improvement.

In late 2022, Teva api completed a $23 million investment in Debrecen, Hungary, with the aim to expand its capability to supply active pharmaceutical ingredients for vital medicines needed for organ transplant patients.

This new extraction facility is based in Teva’s Center of Excellence for Fermentation Products, and has been in existence for over 100 years, combining both API R&D and manufacturing and Teva Pharmaceuticals manufacturing. It is the largest development in the past 15 years in API manufacturing at the site.

Why now?

With the considerable advancement of healthcare over the last few years, it became very clear very quickly that there was a huge shortage of life saving fermentation-products. Transplants have become more common place and the demand for products to prevent organ rejection has therefore increased.

It was understood that the company needed to urgently increase capacity in order to produce the APIs needed to ultimately supply the end patient with the medicines they need.

With this new plant, Teva api will be able to significantly increase our production capacity for active pharmaceutical ingredients, ensuring the security of medicine supply in Europe and worldwide.

The opening ceremony was held in December, with many executive members of the team flying in to be present. The ceremony included the heartwarming gesture of the team signing a heart with a handprint, particularly appropriate since the plant’s main products, in their final dosages, support transplant patients.

Without a doubt, COVID-19 has changed nearly every aspect of our daily lives… from our personal lives to our professional lives. No area remains untouched from the impact of the pandemic. All industries, in particular the pharmaceutical industry, faced an unprecedented set of challenges.

Drug manufacturers and API suppliers were deemed essential industries that the world looked to in order to quickly provide treatments, cures, and vaccines to fight the disease. This renewed focus on pharma not only showed new opportunities that were suddenly created in the market, but also exposed fragile weaknesses in the supply chain.

Trends in the API industry may no longer be trending, and other more pressing matters have taken center stage. As we hope to close the book on COVID, we are now faced with a potentially devastating conflict in Eastern Europe.

Trend #1: Repatriating API supply

At the outset of COVID-19, while there were still many uncertainties about the disease, there was an immediate spike in the demand for various APIs, especially antibiotics and other anesthesia-related products to allow intubation for people on respirators.

It became clear that the raw materials, intermediates, and finished API for these products were sourced and manufactured almost exclusively in the Far East. Governments realized this the security risk associated with being so dependent on foreign ingredients that they made a priority to understand the implications of repatriating API supply.

The US government made available hundreds of millions of dollars to help manufacture pharmaceutical chemicals locally. In India for example, they realized that approximately 90% of the APIs used to manufacture antibiotics was imported. The government there began aggressively implementing a policy to increase local output.

In Europe they began consultations about the possibility to relocate API manufacturing back to the EU. As recently as late March 2022, the French government announced that it is prepared to buy 12% of a French API manufacturing company when it will be publically listed later in the year. A move like this will support the country’s sovereignty in the critical domain of pharmaceuticals.

Of course, all of these initiatives cost large sums of money and take years to implement, so the long term effects are yet to be seen.

Trend #2: Inflation, energy costs & the great resignation

One does not have to look far to realize the price of everything is increasing rapidly.
Inflation in the United States alone is at a 40 year high. This is a result of several factors, of which the three main ones include: printing money to pay for COVID-related relief programs, surges in demand unable to be met by supply, and soaring energy costs. These impact the cost of virtually every product, either in the actual production including the labor, or the transportation.

As the developed world attempts to shift to renewable, ‘clean’ energy, oil and natural gas remain the dominant forms of energy. The new conflict in Eastern Europe is causing a shock to the energy markets not seen in some time.
On the topic of labor, a unique phenomenon dubbed by economists, “The Great Resignation”, took place where employees worldwide are resigning from their jobs with no new job necessarily lined up. This may be caused by COVID-19 stimulus payments, fear of the pandemic, wage stagnation, among other things.

This phenomenon has caused labor shortages, and in theory, should result in higher wages as firms attract workers, driving up costs and further stimulating inflation.

To summarize, API production costs are increasing, as well as the costs for getting the API to the customer’s plant where it will be manufactured into the finished product.

Trend #3: Environmental Social and Governance (ESG)

Throughout all of the chaos and uncertainty of the past few years, one important item has continued to garner the attention of leading organizations in many industries. Companies are making commitments and investments in ESG matters.

For API companies especially, their effects on environment and society can be profound. Efforts to minimize impacts on climate change through reduced greenhouse gas emissions, including reductions in energy use, and overall increased use of renewable energy are priorities for forward thinking API companies.

From a social perspective, ensuring that pharmaceutical companies have steady supply and quick access to their API to support the lives of their patients in an equitable way. Ensuring that business is conducted in an ethical and compliant way, with proper quality and data privacy systems in place.

At Teva api, we’ve set ambitious ESG goals for ourselves. We’re putting a huge focus on minimizing our impact on climate change through reduced greenhouse gas emissions, including reductions in energy use and an overall increased use of renewable energy. Two of our main targets are to reduce facility water use by 10% by 2030, and to reduce greenhouse gas emissions by 25%.

ESG remains an emerging topic that will become more and more important with time.

Trend #4: Digitization

If the world was digitizing quickly before COVID, the pandemic shifted things into hyper drive.

People were suddenly spending even more time in front of their computers and mobile devices than before. When the pandemic first hit, digital tools were quickly deployed and virtual meetings replaced face-to-face interactions. It became more important than ever before to have a strong online presence.

For companies, having a comprehensive digital strategy became a differentiating factor in the marketplace. A well-developed corporate website is no longer sufficient. Companies must have a strong social media presence to better engage with their customers and understand them. Depending on the type of company, a customer portal may want to bring even more added value to the customer, with live data and information about their ongoing business.

So, how will all these trends influence the future of API production?

It’s hard to know. We cannot of course predict the future, and the trends we bring here are a result and analysis of our global presence and the support we provide to leading pharmaceutical companies, but we have outlined in broad terms how we see the market trending.

We see these trends as inevitably meaning closer partnerships between API producers and the pharmaceutical companies. R&D expertise, quality control and product purity are the result of know-how, hard work and common understanding. Data integrity requires the sharing of technologies and customized software. New APIs, no matter what technology is used to develop and manufacture them, require API producers to enter into very close working partnerships with the pharma companies

At the core of this relationship is partnership, trust, communication, and a dedication to quality, regulatory compliance and data integrity.

For a more detailed analysis of your particular area of API manufacture, compliance or data integrity please contact us. Our team of experts is on hand to help you with all your API needs.

Written by Samson Ponselvan, Senior Director of Regional EHS, and Venkat Pudipeddi, Director of HR in India & China.

As the pandemic broke out globally, emergency response teams sprung up everywhere — and Teva api was no different. The Global Situation Room (GSR) was established in early March 2020 to align and guide all Teva sites globally throughout the duration of the pandemic, and each country set up its own Country Situation Room to deal with requirements at the local level.

In India, a unique challenge faced the leadership due to the country’s sheer size and diversity of Teva’s operations and business units. This blog will discuss the journey of the India Situation Room (ISR), and the measures that were (and are still being) taken to provide employees with a safe and comforting environment during these unique times. It will also describe the actions implemented to ensure the continuous delivery of much-needed medicines around the world.

The India challenge

Being that Teva operates in the ‘essential services’ industry, the team was driven with the objective of providing a working and sustainable solution for employees during these extraordinary times, the India Situation Room was set up to ensure the safety and health of all Teva employees in India, and to maintain business continuity for our India-based operations.

With 11 sites across six Indian states, this operation was certainly no easy feat to get off the ground. The ISR consists of more than 25 people in the leadership team, including all the site leaders and work stream leaders from all our facilities in India. In addition, each site, in each location, established its own Site Situation Room led by the individual site leader.

General COVID-19 guidelines come from Teva’s Global Situation Room, and are then reviewed by the ISR and synced with the Indian Government’s guidelines.

Powering on while keeping safe at Teva India

Essentially, there are two main objectives of the ISR. The first is to safeguard the health and safety of all employees, contingent workers, and contractors. Without the people, nothing can continue.

The second main objective is so ensure Teva’s resilience — business must carry on, come what may, so that patients don’t end up losing out. With these two objectives in mind, the ISR had, and still has, multiple key tasks facing them.

• Have one consolidated approach of existing and potential threats, opportunities, and mitigations aligned with local India government and Teva corporate guidance.
• Take care of the health and safety of employees (especially those diagnosed with Coronavirus), the community, and the business.

How we do it

• 
  

  Leaders constantly touching base

  
  

The India Situation Room had a mandatory meeting each morning to review the situation as the virus was spreading across the country and the lockdown being imposed. The team worked hard to establish a leadership tone that balanced the two main objectives of safety for employees and business continuity. These calls have now become weekly, as we’ve become more familiar with the situation and how to deal with it.

Daily ‘safety moments’ are a core element of these calls. Each leader takes a turn to give a short presentation on a safety-related topic, raising awareness on the constantly changing situation and the proper response to it. These ‘moments’ range from discussing employee health and sanitization methods to product/service safety.

• 
  

  Building the medical/health infrastructure

  
  

The team stayed ahead by equipping the medical doctors & staff in the Occupational Health Centers in each of the manufacturing sites to respond better in case of an emergency and to ensure a safe environment for employees.

For example, pulse oximeters were procured, as well as temperature guns and other special personal protective equipment.

• 
  

  Creating proper protocols

  
  

Protocols were created for employees returning to work after having the coronavirus, as well as for cases that are suspected or confirmed. Mock drills were also organized. Throughout this period, and especially during the beginning months, the Occupational Health Center staff worked on building up their emergency response capabilities.

• 
  

  Keeping the information flowing globally

  
  

It’s been hugely important for us to keep the global team up to date about the situation in India, and in turn, we’ve benefited from a seamless flow of guidance and information – resulting in employee safety and healthy site operations. The global team has aided the India team in providing support to each person suspected of having the virus, or those who actually did contract it. The empathy given also helped employees overcome any stress in these disruptive times.

• 
  

  Risk assessing new technologies

  
  

With the advent of the pandemic, many new technologies mushroomed in the market. Some of these were not adequately tested for efficacy or safety on employees’ health & safety. The team evaluated each of these for its efficacy before deciding whether to implement it or not.

For example, the team proactively evaluated the sanitization tunnels spraying the disinfectants and decided against the implementation. It was also discontinued by the government and others where it was implemented and thus validating the keen evaluation by the India Situation Room.

The team proactively evaluated this technology and decided against the implementation. It was later discontinued by the government and other companies where it was implemented, thus validating the ISR’s decision.

Inspiring confidence in our employees

The situation in India hasn’t been easy. Different states have been affected differently which has an impact on our operations. Due to the population density in India, COVID-19 has been extremely intense. India was one of the few countries that announced an early and extended lockdown, with an interstate lockdown within the country.

There’s also a huge diversity of population, with a stark contrast between rural and metro India and the levels of awareness on COIVD-19 between the two. All these factors have placed a strain on workers across the board – whether at Teva or elsewhere.

This unified Teva approach in responding to the situation — the leadership tone, transparency and commitment by all during these times helped instill a strong safety culture across the sites. Openness to hear employee’s ideas, suggestions and concerns through various channels such as open houses, one-on-one meetings, and town halls has helped instill this safety culture.

Some ‘smaller’ actions that were implemented included safety-themed posters, in both English and the local language, that were put up everywhere; mock-drills took place to practice for all sorts of COVID-related scenarios; and a ‘Zero Contact’ drive took place to ensure social distancing among employees.
Another extremely impactful initiative that was implemented was introducing insurance programs for all workers (both employees and contractors), that guaranteed them solid cover in the event of contracting the virus. During the lockdown, food and other basic necessities were also provided to those workers who needed it, as well as transportation to get to and from work. We’ve heard from many workers that, without this aid, they simply wouldn’t have managed and/or felt comfortable coming in to work.

This culture of ‘caring’ supported employees and the contingent workforces with appropriate medical support and addressed the basis needs during the lockdown, thus creating a rewarding environment.

Teva during these extraordinary times extended support to the migrant population that was stranded during the lockdown with food, stood by the medical fraternity by providing PPEs and helped the contingent workers with grocery supplies. The outreach programs not only created impact on the society but also helped building awareness and commitment to providing a safer environment for each other.

Looking ahead…

In these unprecedented and challenging times, the India Situation Room has done, and is still doing, a commendable job of coming together and facing whatever daily challenges crop up.

The ISR platform has paved the way for sites, cross-functional teams, and individuals to work together, strengthen our systems, and reduce risk to safety, health and welfare all round.

The sheer magnitude of this cross-business operation, and the subsequent success of it, has prompted India’s leaders to take this working model forum forward. In the last couple of months, a Crisis & Business Continuity Management Team has been established, with the aim of providing business continuity planning guidance to sites and teams across India.

 

At Teva api, we are dedicated to leveraging our corporate resources and expertise to promote healthy communities all over the world. Our ambitious, wide-ranging Environment, Social and Governance (ESG) activities and our commitment to sustainability has just won us the 2020 EcoVadis Silver medal, reflecting our ongoing efforts to cultivate responsible business practices and positive social initiatives.

As the leading international supplier of quality active pharmaceutical ingredients, we support 75% of the top 50 global pharmaceutical companies via 16 manufacturing plants, five R&D centers, and seven sales offices, accumulating an annual $745.5M in sales. Serving nearly 1,100 customers in more than 75 countries, we are profoundly aware of our deep responsibility to not only comply with all applicable laws and regulations, but also actively work to exert a positive impact on the world around us.

Teva was awarded an EcoVadis 2020 Silver Medal for responsible conduct in environment, labor and human rights practices, ethics and sustainable procurement– a score placing us in the top 24% of all pharmaceutical companies rated by Ecovadis.

EcoVadis is the world’s most trusted provider of business sustainability ratings for global supply chains, with its famous scorecards providing invaluable, detailed insight into environmental, social, and ethical factors. Receiving the EcoVadis Silver medal is not only a huge honor for Teva and Teva api, but also confirmation that we are meeting our ambitious ESG performance goals.

The Teva 2019 ESG Progress Report, which was published a few months ago, clearly illustrates our steadfast commitment to patients and communities everywhere, in multiple areas:

Quality APIs

As generics play an increasingly significant role in global healthcare, questions are continually being raised about product quality. Are these affordable alternatives actually as safe and effective as their brand-name counterparts? Throughout the business landscape, and particularly where health is concerned, customers desire to collaborate with companies that not only supply reliably high-quality products, but also behave in a socially-responsible manner and have a positive impact on the environment.

Teva api, and Teva as a whole, exemplify the very best in both product quality and responsible citizenship. Our mission to improve patient lives and promote global health always comes first, empowering our dedication to absolute product quality and safety. Some 200 million people take our medicines daily, and we carefully monitor all our products throughout their entire lifecycle via our pharmacovigilance division, in strict compliance with global regulations.

In 2019, we gained approvals for 1,000+ generics, helping to make treatments more affordable. We also achieved significant improvements in safety management and environmental sustainability, while launching unique ESG activities that are driving meaningful change in communities worldwide.

Access to Medicines

Even the best, most effective medications become useless if patients have no way to access them. Although generics have revolutionized healthcare for millions of patients around the globe, dramatically reducing costs across the board, the World Health Organization (WHO) estimates that more than 50% of people still lack access to critical health services.

As the world’s leading provider of generic medicines, we continually strive to improve vulnerable populations’ access to quality healthcare and medicines, including those on the WHO’s Essential Medicines List, and expand our generics pipeline.

We recognize that healthcare access is a complex global issue that can only be addressed through diverse, sustained efforts that actively engage governments, NGOs, humanitarian organizations, healthcare professionals, and pharmaceutical companies in cross-sector partnerships.

In 2019, Teva donated $246M worth of medicines to patients around the world and partnered to address childhood cancer medicine shortages by supplying 17,000 vials of 13 medicines in Ethiopia.

Childhood Cancer Medicines Initiative

Teva manufactures 84% of cancer medicines listed on the World Health Organization’s (WHO) Essential Medicines List (EML), so when Ethiopia faced a shortage of childhood cancer medicines, we formed an initiative with Access to Childhood Cancer Essentials (ACCESS), Direct Relief and the Ethiopian Pharmaceutical Fund Supply Agency (EPFSA) to address the problem.

We identified 13 Teva cancer medicines from the EML and sent 17,000 vials to Ethiopia within six weeks—a process that can typically take upwards of six to nine months. When the US faced a shortage of Vincristine, a childhood cancer medication, Teva announced that it would re-introduce the product, manufacturing it at one of its US plants, in order to provide the product to the market faster. Teva hopes the reintroduction will help address the shortages and bring this life-saving medicine to children in need.

Environment, Social, Governance (ESG) — Going Forward

As our 2019 ESG Progress Report describes, Teva and its pharmaceutical ingredients division, Teva api, have made great strides forward in endorsing meaningful social initiatives and research dedicated to improving the health of underserved communities worldwide. However, we also recognize that this is an ongoing process.

As Kåre Schultz, President & CEO Teva Pharmaceutical Industries Ltd., said:

“Looking to the future, we will continue to advance our ESG efforts to create value for our investors, employees and many stakeholders. We will strive for full compliance, while demonstrating integrity, ensuring the quality of our medicines and keeping patients at the heart of what we do. .”

 

Completing a Good Manufacturing Practices (GMP) audit report prior to 2020 was simple. Companies had many ways to get theirs done, and a large percentage opted for performing their own onsite audits at their suppliers’ facilities, and then putting together the report themselves. This year however, with travel so limited, this option is difficult if not impossible.

GMP in a nutshell

Good Manufacturing Practice (GMP) ensures products are constantly produced and controlled to the quality standards appropriate for their intended use and conform to the regulatory requirements set by health authorities. GMPs are essential to any manufacturing industry and are often required to be implemented by national governments.

The tenets of GMP mainly relate to:

• standardization of product quality (consistency, efficacy, shelf-life, manufacturing practices)
• assurance of product safety (sterility, content consistency/active ingredients, lack of contaminants)
• good documentation practices (GDocP) as a crucial part of assessing quality controls, testing reports and more

GMP Audits

A GMP audit is a very important regulatory process. Pharmaceutical manufacturers are required to carry out GMP audits of their suppliers or have audits conducted on their behalf by qualified, experienced auditors. Multiple checklists exist online to guide companies through the audit. There are also many external, independent companies out there that provide GMP auditing services for pharmaceutical manufactures to meet their audit requirements for regulatory authorities.

Whether you choose to use an independent auditing company, or perform the audit yourself, is entirely up to you. Some of the elements to take in to account are budget, time, and availability to travel. The latter is clearly a major consideration in 2020.

Our solution for you during COVID

Luckily, during these challenging times, we have the perfect solution for you! Several independent auditing companies have carried out full audits at the majority of Teva api manufacturing sites, and can provide you with personalized and comprehensive reports dedicated to the areas most relevant to your operations.

The reports focus on our facilities’ quality management systems, cover a large number of products, and are recognized by QPs and regulatory authorities globally. So you’ll essentially be able to fulfill your regulatory requirements without the need to travel.

For more information about this service and the various auditing companies, please contact us .
If you’d still prefer to perform an onsite audit or remote desktop audit, it may be possible, depending on individual circumstances. Please do not hesitate to contact us.

Happy auditing!

Here at Teva api, we’ve had a significant operational presence in Europe for many years. Over the last few months, as COVID-19 spread relentlessly across the world, we’ve gained a deeper understanding of just how valuable this presence is, and how we could optimize it to best support our supply network and ultimately provide better service to our customers.

Teva api in Europe

With approximately 50% of our manufacturing sites in Europe, including in Italy, Croatia, Hungary, and the Czech Republic, Teva api has always had a strong European presence.

In fact, Europe is a global hub for API production in general. Data shows that Europe remains a globally competitive producer of generic medicine and APIs, both for its own market and for export.

At Teva api, our network of 16 sites worldwide spans multiple countries and continents, and our dynamic supply chain moves throughout. This is vital in order to ensure diversification.

Keeping products flowing during COVID-19

When the pandemic hit, our diversified manufacturing presence meant we did not have to rely on one country or one site for all our production needs. In circumstances where the same product could be produced in multiple sites, we were able to supply it to customers from the one that was easiest to access at the time (where authorizations already existed). Our strong presence in Europe meant that we were able to continue an ongoing supply of products within Europe and globally while dealing with all the logistical challenges that arose. Our diverse manufacturing footprint provides a key advantage to our customers — and as a result, the end patient.

Our very experienced and well-connected logistics team managed to find creative ways to identify routes and deliver products, despite closed borders and canceled flights. Whether it was a more costly route or an unconventional route that took longer, the team made sure to get each order to the customer.
Our strong quality systems and robust regulatory affairs team were able to provide great support during this global pandemic, and work collaboratively with regulatory bodies in Europe and worldwide to facilitate continuous supply of essential medicines to patients globally.

Protecting our people and our products

From the start of the pandemic, we took precautionary measures to ensure that both our people and our products were protected. We managed to contain the impact of the virus on our levels of production and supply of products with three primary protective measures:

1. Smart working: We defined the people who were essential to keep production and operations moving, as well as the functions necessary to support those people. Only these individuals were permitted to physically go to the sites. Everyone else worked remotely. Limiting the number of people at the sites was fundamental to avoiding unnecessary interaction and greatly reducing the potential transmission of the virus. For those who worked remotely, our IT team made sure that everyone was equipped with all the right tools necessary to ensure uninterrupted work.
2. Healthy working: We had to ensure that our employees remained healthy. We introduced prescreening of anyone coming to the site so that no one came in who represented a risk. This included a questionnaire, temperature monitoring, etc. We also implemented an enhanced medical service at each site, which was especially important at the beginning, when the virus gained momentum in Italy. A healthcare professional provided information and examinations so that employees would feel a sense of confidence that they were being well cared for.
3. Safe working: We successfully secured personal protective equipment, e.g. masks, overalls, and gloves, for all employees on site, even when this was hard to come by. We also increased the frequency of sanitation in our facilities – cleaning and disinfecting more regularly, giving more access to sanitizers, and continuously running communication campaigns about social distancing and safe working practices. As safety protocols were issued by the government, we implemented each one in our facilities.

The impact on future manufacturing in Europe

COVID-19 has definitely changed the playing field. It will — and already has started to — stimulate companies and policy makers to reflect on the criteria that they are utilizing to source their products. If these expand to include ease of access, availability, and flexibility, then inevitably it will mean that certain manufacturing will remain in western countries, since it may not be sensible to rely solely on one region. To encourage production in Europe, policy makers need to put incentives in place to secure European investment in API manufacturing, thereby securing Europe’s manufacturing competitiveness globally. The European Commission is currently reflecting on a pharmaceutical strategy for the years to come and will drive policy initiatives which are crucial for the sustainability and resilience of API manufacturing – I am looking forward to seeing where that leads.

For example, it is important that policy makers strike a balance between the cost and availability of products in all markets, and understands the dynamics associated with that. For pharma companies to have access to APIs and for patients to have access to medicines, manufacturing and logistics need to be diversified and economically sustainable. I think that it is this realization, and the risk of future pandemics or significant world events, that will encourage countries to become more self-sufficient.

Where we’re going from here

The discussions about supply security have already started at Teva api. How do we optimize our network to mitigate future risks? How do we leverage the strengths we have based on the technologies and demographics of our products? Perhaps we should introduce measures that allow for additional flexibility, and award those who are complying with Europe’s access equity, resilience, and green ambitions — topics that policy makers should perhaps reflect on in cooperation with the sector.

As a manufacturing network, we want to be as efficient and cost-effective as possible, but these two factors do not automatically translate into access to essential medicines. Cost and efficiency are only a competitive advantage when coupled with a reliable and robust supply network.

As we review our network and move forward, we take strength in looking back at the past few months and what we have managed – and are still managing – to accomplish.

Onwards and upwards!

On April 1st, 2020, Brazil’s ANVISA published new landmark regulations referring to active pharmaceutical ingredients (APIs). This new set of rules consists of three separate guidelines for local pharmaceutical segment stakeholders, known as “RDCs”. These are RDC 359/2020, RDC 361/2020 and RDC 362/2020, and they represent a complete overhaul of the API regulatory landscape in Brazil. The aim is to ensure that all Drug Master Files (DMFs) for future applications are reviewed under these provisions.

ANVISA has made a clear move towards regulatory convergence over the past few years. In 2016, it became a member of the International Council for Harmonization, and, a few months later, signed a memorandum of understanding with the European Directorate for the Quality of Medicines in 2017. When examining the new regulatory framework, we can clearly notice the influence of exchanges between ANVISA and these organizations.

The paradigm shift embedded in the landmark new regulatory framework will bring about a much-anticipated direct interaction between the authority and the DMF holder/API manufacturer. In addition, it will streamline the process for subsequent petitions using any given prior-reviewed DMF — or as, ANVISA calls it — DIFA (Dossiê do Insumo Farmacêutico Ativo). At the end of a successful review, the DIFA holder will receive a certificate of suitability from ANVISA. This certificate is called a CADIFA (Carta de Adequabilidade do Dossiê de Insumo Farmacêutico Ativo) which is equivalent to the Certificate of Suitability (CEP) in Europe.

For this new chapter in Brazilian regulations, Teva api brings to the table:

• An extensive knowledge of similar centralized procedures for DMF review in main markets (such as EDQM in Europe and GDUFA in US).
• A strategically designed structure for global regulatory affairs, which includes a specialized unit for electronic submission of documentation.
• An expert in Brazilian regulatory affairs who will recruit Portuguese-speaking personnel located in São Paulo, Brazil.

Our goal is to set the stage for our customers to operate efficiently and successfully under these new regulations, making for the blueprint of a sustainable and lasting partnership in Brazil.

The global market for the manufacture and supply of API’s is changing rapidly and there are many factors influencing these changes. But precisely what are the major trends you should know and be aware of, and how can you use them to your advantage? In this article Teva api gives you the latest overview.  

A key trend in the global API market is increasing focus on innovative formulations in generics development. Demanding conditions call for advanced treatments using complex molecules.

API is no longer constrained to commodity treatments, and leading API manufacturers are pivoting to highly complex technologies such as peptides, oligonucleotides and sterile API.

Teva api is investing heavily in new technologies to create products used to treat complex medical conditions such as cancer and immunological conditions and other rare diseases.

Buying API’s produced in Asia has its pitfalls

More and more of the world supply of API’s will be manufactured in Asia, where the talent pool of engineers and scientists is high and where the cost structure for manufacturing, labor, materials and equipment is relatively low.

There are a number of issues already rising from this eastward migration. Concerns over quality have lead the US FDA and the European authorities to issue fines and import bans due to major issues concerning the quality and most worryingly the falsification of manufacturing and testing data.

Looking at statistics from the past five years, the number of API suppliers to come under scrutiny by the US FDA has increased[1]. As there is a steady increase of API volume there is also an increase of suppliers who like to qualify for the worldwide market leading to, an increase in the number of critical issues found, mostly due to fact that the quality systems of these companies are not yet matured.

Flight to quality

One clear result of the regulatory issues surrounding API production in Asia has been a “flight to quality”, meaning that many pharmaceutical companies have turned to trusted partners like Teva api, to produce their API’s. Until full compliance is possible, most pharmaceutical companies are expected to place their business with API manufacturers who are already used and dedicated to worldwide standards and processes and to resolve issues in the region.

How will these trends influence the future of API production?

These trends may seem rather chaotic. However Teva api sees these trends inevitably meaning closer partnerships between API producers and the pharmaceutical companies. R&D expertise, quality control and product purity are the result of know-how, hard work and common understanding. Data integrity requires the sharing of technologies and customised software. New API’s no matter what technology is used to develop and manufacture, require API producers to enter into very close working partnerships with the pharma companies in order to develop methods of Api production, R&D, certification and product launch. The more complex the nature of the API, the closer the understanding and co-operation between producer and customer has to be. At the core of this relationship is partnership, trust, open communication, a dedication to quality and regulatory compliance and data integrity.

To find out more about Teva api’s global leadership in these fields please click onto your topic of interest to read more:

Partnership

Open communication

Quality

Regulatory compliance

Trust & Data integrity

Teva api facts and figures

 

Teva api have a dedicated team of experts on hand to help you with your API needs. We cannot of course predict the future, and the trends we bring here are a result and analysis of our global presence and the support we provide to most of the leading pharmaceutical companies, but we have outlined in broad terms how we see the market trending. For a more detailed analysis of your particular area of API manufacture, compliance or data integrity please contact us.