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Indena Centennial: Finding Quality in Nature and Science


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In a world in which nations and companies compete for and capitalize on natural resources, sustainability may not always be a top consideration. This makes the qualities of a company like Indena SpA even more prescient. It touts a decades-long commitment to sustainable sourcing and views the connection between science and the natural world as a means to nurture invaluable resources that are of utmost importance for human health.

The Milan, Italy-based pioneer in identification, development, and production of botanical active ingredients celebrates its centennial anniversary in 2021. That is a rare industry landmark. The company was founded in 1921 as Inverni Della Beffa at the dawn of an era of burgeoning modernity and optimism. Since then, it has weathered a century of wars, economic crises, scientific discoveries, and astonishing technological advancements. Today, Indena still stands as a company that is thriving and relevant.

“Today, we manage, from our headquarters in Milan, four production sites around the world and five international subsidiaries, employing a total of more than 900 people (most of them in the strategic fields of Innovation and Quality),” wrote Indena CEO Daniele Giavini (email, April 28, 2021). “We also have about 100 patent families and more than 1,000 scientific studies published with qualified research groups.”

Despite its deep Italian DNA, Indena has always valued international expansion, and today international markets, including collaborations with several partners in innovative fields, account for about 90% of its business, Giavini added.

From the beginning, the founding fathers of the company, Carlo Boccaccio Inverni and Biagio Alberto Della Beffa, brought a new, modern approach to the business of medicinal plants. Their initial aim was to provide not only high-quality medicinal plants but also standardized plant extracts, which helped pave the way for enhanced chemical characterization and more accurate dosing.1

Since its early days, the company has had many firsts. Inverni Della Beffa was a pioneer in standardized extracts, and Indena became the first company to introduce the concept to the US market.1 During the 1960s, the growing insights of its scientific team led to the publication of the renowned reference book Medicinal Plants: Their Chemistry, Pharmacology and Therapy (Messaggerie Italiane, 1962).2 In the 1970s, Inverni Della Beffa was the first company in the herbal industry to use mass spectrometry (MS) and nuclear magnetic resonance (NMR) machines in its quality-control laboratories, which helped scientists better analyze the structures of complex plant extracts and overcome the skepticism of those in the conventional pharmacology field.2

The importance of such developments is far reaching. “Standardization means that you can trust your botanical ingredient in terms of safety and effectiveness,” wrote Antonella Riva, Indena’s product research manager (email, March 3, 2021). “A standardized extract is a complex matrix well characterized for its phytochemical profile. This profile [is] the identity card of the Indena extract and will be the same, batch after batch, allowing customers and consumers the same quantity of active principles,” she explained.

Other important firsts over the decades include Indena’s biomedical documentation, such as research studies that support the use of the company’s ingredients for various health conditions. Indena also paved the way for increased bioavailability of botanical ingredients with the development of a proprietary, scientifically proven food-grade delivery system, Phytosome, which optimizes bioavailability and efficacy and has allowed for the translational success of natural products like curcumin and quercetin, Riva added.

Today, the company continues to make significant advancements. Most recently, it announced it has become the first Italian company authorized by the Italian Ministry of Health to manufacture cannabinoid-based cannabis (Cannabis sativa, Cannabaceae) extracts. Indena received additional permission from the Italian Medicines Agency (AIFA) to manufacture these extracts, making it one of only a few companies in the world to produce cannabidiol (CBD) for the pharmaceutical market.3

In 1977, Inverni Della Beffa became Indena (INdustria DErivati NAturali) and invested in technological innovation for development of botanical derivatives like extracts, while the production of finished plant-based, mainly prescription medicines, was maintained under the brand name of Inverni Della Beffa.1

Indena’s success is deeply rooted in its foundational pillars, which include quality, research, technological innovation, and solutions designed to make safe and more effective products available for peoples’ wellbeing, noted Francesca de Rensis, Indena’s marketing director (email, March 3, 2021).

“Attention to quality and the quest for excellence have been company hallmarks since the beginning, as well as the innovative approach to business, which has characterized the company throughout its history,” de Rensis wrote. Today, she added, Indena “continues to draw inspiration from the spirit of its founders a century on. Their vision, forward thinking, scientific rigor, and stability remain the ingredients of quality for a major player in a global market.”

By the 1980s, Indena was experiencing growth and an expanding global footprint. The company was at the forefront of product research and development and produced complex extracts such as multicomponent ingredients used in food (dietary) supplements. In 1989, the company opened Indena USA led by Greg Ris, vice president of sales, to introduce the concept of standardized herbal extracts in the US market.

Preserving success also means addressing many challenges. For example, it is difficult to maintain continuity in personnel and vision. For Indena, this came from the Della Beffa family: the company’s origin and inspiration, the engine of its development, and a crucial source of internal cohesion, Giavini explained. The company has always been aware that establishing structured corporate governance would provide the opportunity to innovate the typical relationship between family and business that is common in Italy, he added. “The Della Beffa family has always had a long-term vision for the company’s growth,” Giavini added. “For this purpose, top management figures were entrusted with leading the organization and [were] stably kept in place. This is a key factor that allowed Indena to grow and succeed.”

This consistency in management and philosophy helped Indena nurture strong relationships around the world and a reputation for integrity and leadership. “A longtime member of [the Council for Responsible Nutrition (CRN)], Indena is one of the highest quality herbal ingredient firms in the industry and widely respected as a leader in quality and innovation for both nutraceuticals and pharmaceuticals,” noted Steve Mister, president and CEO of CRN, a leading industry trade organization in the United States (email, April 20, 2021). “As Indena is based in Italy, CRN has had the privilege of working with Greg Ris, the company’s lead US contact, as well as other Europe-based staff. We congratulate Indena on its centennial anniversary and look forward to continued collaboration in the future.”

Loren Israelsen, executive director of the United Natural Products Alliance, an industry trade group, also praised Indena’s engagement with the US market and its experienced staff’s deep understanding of the United States’ regulatory and compliance requirements. “This is quite unusual for a non-US-based company to have that level of domestic engagement and competence,” he wrote (email, March 15, 2021).

Israelsen called quality the company’s chief legacy. “Indena has a golden reputation for quality that is so trusted that many companies use Indena extracts as the benchmark against which other ingredients are judged,” he wrote. “Indena’s [research and development] has led to breakthroughs in botanical extract efficacy. They relentlessly pursue innovation and technological improvements, which is one of the reasons they remain such a vital company.”

The Meaning of a Century

Perhaps the underlying secret to Indena’s success goes back to its vision about nature and science. “Since the beginning of our company’s life, Indena’s approach to phytotherapy added something fundamentally new to the medical knowledge of the time. Phytopreparations were being scientifically screened in the laboratory and would become companions to modern medicine,” wrote Stefano Togni, Indena business development and licensing director (email, March 3, 2021). “In other words, individual active ingredients and their specific pharmacological profile were being identified, as were the multicomponent extracts with a much greater degree of complexity. This valuable information, supported as it was by scientific criteria, was made available to the public and professionals alike.”

In the case of a company, one could suggest many different attributes as important to stay relevant for 100 years. “Few companies survive to be 100, and far fewer natural product companies have been able to adapt and evolve to be world leaders in the way that Indena has,” Israelsen noted. “There are a few other examples. Schwabe, of Germany, is 150+ years old, and Indiana Botanic Gardens is 110+ years old, but this is such a rare achievement. It certainly deserves to be celebrated.”

Gabriele Fontana, Indena – business and innovation intelligence, said that the company’s history has shown Indena to be a reliable, financially solid, and flexible company, ready to adapt to environmental changes. “Being a company with a century of experience means being a solid company that has gone through a hundred years of social, economic, financial, and legislative changes,” he wrote (email, March 3, 2021).

“The solidity [derives] from … being a family company since its foundation and is proof of its healthy way of doing business. The flexibility derives from its proprietary technical know-how accumulated in 100 years of activity. The course of the last century has seen the tightening and sharpening of regulatory and quality requirements by authorities, and Indena has always been able to invest in its technology and meet the demand. There is no company that can survive for such a long period of time and miss just one of those attributes.” Fontana added.

When asked what sets Indena apart, Ris suggested that it comes down to the company’s pharmaceutical roots. “We have higher standards and quality systems we adhere to. I highly doubt if other botanical companies are screening for 450 pesticides,” he wrote (email, February 25, 2021). Secondly, he added, Indena is a privately owned business, and “the Della Beffa family from the beginning insisted that the company do it better than anyone else. Second best was never an option.”

Indena: A History through Plants

Indena has experienced many key advances in its history, and its journey is perhaps best memorialized by its enduring bond with the plant world and the important botanical derivatives it has developed for the pharmaceutical and nutraceutical industries.

The company founders brought intuition and vision to the business, and their revolutionary approach to the medicinal plants sector brought immediate and ongoing significance to the market.3 This helped create a new scientific and industrial model that would lead to the standardized production of active principles from plants. One of the first was the horse chestnut (Aesculus hippocastanum, Sapindaceae), often called the “green umbrella of boulevards,” lining the streets of many European cities.2 Among the company’s first products in the 1920s was an extract known as escin derived from the bark of horse chestnut branches. The vasoactive substance was used to produce preparations for edema and capillary fragility.4 The development of this raw material illustrates the importance of the scientific and quality strides from the early days of Inverni Della Beffa.

The company was also consistently ready with the right botanical ingredient at the right moment. Such was the case in the 1940s, as war descended on Europe. To ensure the safety of its production and employees, Inverni Della Beffa left its Milan facility for a temporary location in the hillside town of Alzano, in the province of Bergamo.2 These years of hardship and disruption prompted demand for valerian (Valeriana officinalis, Caprifoliaceae), a medicinal plant long known for its calming properties.5 Even through this difficult time, Inverni Della Beffa met this demand and provided a gentle remedy to help ease the tension of both military and civilian populations at the time.

Scientists at Inverni Della Beffa had also discovered that valerian’s qualities were not caused by a single active ingredient but rather the synergism of several compounds.5 This discovery compelled the company to begin producing standardized fluid extracts in addition to isolated active ingredients. This also led to production of purified natural derivatives reduced to a single molecule that formed the basis of conventional pharmaceutical medications with well-characterized applications.

With the war over, the 1950s marked a period of expansion, change, and opportunity for Inverni Della Beffa. During these years, the company expanded internationally and continued to add to its body of research.2

One of the actives that became important at the time was from Gloriosa superba (Colchicaceae), a climbing plant sometimes referred to as flame lily, with a long stem and large orange-red flowers. This plant contains the alkaloid colchicine, which initially was derived from the autumn crocus (Colchicum autumnale, Colchicaceae) and, despite its toxicity, has well-documented anti-inflammatory properties that are useful for the treatment of gout.6 It eventually was discovered that flame lily provides other health benefits including muscle-relaxant properties. However, because thiocolchicoside (a derivative of colchicine) was available only in the seeds, much of the unused portions of the plant were wasted. This prompted Inverni Della Beffa scientists to develop a new fermentation process to transform colchicine present in the plant into thiocolchicoside, thus creating the active compound for muscle relaxation more efficiently. This effort was the foundation for the company’s mission to source ingredients sustainably and ethically.

The expansion and development of opportunities continued for Inverni Della Beffa in the booming 1960s, as Luigi Della Beffa took the company’s helm. In addition to producing active ingredients, Inverni Della Beffa began producing finished herbal medicines. A flagship product at the time was the antiarrhythmic agent (used to treat heart rhythm disorders) derived from the roots of Rauvolfia serpentina (Apocynaceae), an evergreen shrub sometimes called Indian snake root that is native to India and sub-Himalayan regions.2 The finished herbal extract contains alkaloids like ajmaline, which can address tachycardia (rapid heart rate), premature heartbeat, and fibrillation (quivering or irregular heartbeat).7

The 1970s was a decade of technological progress across the world and at Inverni Della Beffa. The company began using MS and NMR machines to analyze the structure of complex extracts like silymarin from milk thistle (Silybum marianum, Asteraceae) fruits more accurately. Silymarin has antioxidant actions and is well known for its support and regeneration of the liver.2 This allowed the company to demonstrate a plant’s healing properties in an analytical way. It was to become a hallmark of Indena.

The blossoming 1980s health aesthetic based on natural principles for fitness and diet left Indena poised for further success. There was now demand for complex, effective, well-tolerated plant extracts that could complement synthetic drugs and/or mitigate their effects.2 Indena’s long history of research and laboratory work allowed it to meet this need and demonstrate efficacy of multicomponent derivatives — an important prerequisite for safe and reliable products in the emerging nutraceuticals market.

A plant that exemplified this concept was bilberry (Vaccinium myrtillus, Ericaceae), a shrub-like plant native to northern areas of Europe, Asia, and North America that has been used for medicinal purposes since the Middle Ages.8 Rich in antioxidants such as flavonoids and anthocyanins, it is thought to have benefits for the digestive system, oral health, and vision. In the 1980s, Indena developed a new method to map and characterize the anthocyanins in bilberry, and that method remains an industry standard today.

In the 1990s, Indena continued to invest in botanical research and innovation. The yew tree (Taxus spp., Taxaceae) is another example.2 This long-lived conifer, common in Italy and throughout Europe and North America, is also known to be highly poisonous. However, it contains important chemicals known as taxanes that have promising anti-cancer properties.9

The problem was that taxanes are in the tree’s bark and extracting them meant destroying the entire tree. The need to find a sustainable manufacturing process became urgent at the beginning of the 1990s when the US company Bristol Myers Squibb (BMS) obtained the registration of Taxol®, the anti-cancer agent paclitaxel for ovarian and then breast and lung cancer. Indena was the first company to offer BMS a sustainable plan for manufacturing paclitaxel. First, the Della Beffa family invested in five-year cycle term plantations of yew tree for the extraction of paclitaxel from the bark. Then, Indena researchers were the first to industrialize the extraction of 10-deacetylbaccatin III (10-DAB III, a precursor of clinically used paclitaxel analogs) from the leaves of T. baccata, the European yew tree. That was one of the greatest achievements in the field of industrial natural products manufacturing at that time. The leaves are a renewable source and do not require the sacrifice of the tree. Furthermore, the large-scale availability of 10-DAB III paved the way for the industrialization of the semi-synthesis of the taxane family of drugs.9

According to Giavini, “the cooperation with Bristol Myers Squibb for the industrial manufacturing of paclitaxel was a key turning point for Indena, as it introduced in the company the concept of high-containment facilities [an ensemble of buildings, equipment, devices, and operating procedures in place for handling harmful substances in conditions that are safe for workers and the environment] for highly potent API [active pharmaceutical ingredient] handling. And, beyond that, Indena started a unique experience in dealing with the US regulatory framework for natural-derived pharmaceutical substances.”

Ris also thinks this development was important. “Indena was able to demonstrate to Bristol Myers Squibb … that there was a more environmentally friendly way to collect the active — from needles and twigs,” he wrote. “You create the precursors from this sustainable source and then add the side chain. We became their principal supplier. This also led to a new taxane discovery for Indena and second- and third-generation products.”

Indena Today

These stories illustrate Indena’s century-long commitment to preserving the balance of nature and its ongoing awareness of the connection between the health of people and the planet. The company has also made a commitment to country, people, and corporate responsibility that goes above and beyond business norms. In its literature, the company describes being proud of its past and responsible for its future.

This notion views the nature of business and success as circular, according to Laura Bo, Indena – communications and sustainability (email, March 3, 2021). “Indena has always been conscious of how important it is to preserve the natural balance of nature and how the health of people and planet are strictly interconnected,” Bo wrote. “For a century, the company has been learning from plants, producing precious extracts and derivatives for human health, … guaranteeing the safety of employees and people engaged in the supply chains, [and] safeguarding biodiversity and environment.

“Of course, procedures, certifications, and a dedicated management [team] are essential to reach the goal to contribute to sustainable development,” Bo continued. “This is … why Indena [has] a committee [that oversees] environmental, health, and safety issues with the focus to reduce CO2 emissions and build a circular economy.”

Today, Bo added, Indena considers circularity an innovative and wealthy paradigm that brings together and reconciles nature, technology, and people in a “precious circle and evolutionary journey.” Indena has started a new Corporate Social Responsibility program, which aims to widen this circle and help the company meet its responsibilities to the environment, society, and its stakeholders.

From Ideas to Reality

Indena moves from ideas to practice with the help of bright minds. The company describes its research and development department as “an internal think tank that is dedicated to phytochemical engineering as a means to explore how humankind in the next few decades might take care of its health by reconnecting with the natural world.”10

With a shared belief that nature provides inspiration for brilliant ideas and that there is no limit to what can be achieved, Indena scientists combine intuition and know-how to solve human health issues.10 This involves studying both biological activities and underlying molecular mechanisms to identify new principles.

A big challenge, de Rensis noted, is attracting and retaining skilled workers and understanding that skillsets and thinking styles are essential. “We have a team of key people with soft and hard skills who are committed to a common purpose, performance goals, and approach, for which they hold themselves mutually accountable.”

From there, the company develops new ideas to advance both efficacy and safety of medicinal plant derivatives. For example, Indena’s proprietary Phytosome system for the formulation of extracts uses 100% natural food-grade ingredients to help enhance the bioavailability and pharmacokinetic profile of active compounds.1 This is important, explained Riva, because if a botanical active ingredient is poorly soluble in water, it cannot cross the intestinal barrier and is not able to express its biological activities. “Thanks to our food-grade delivery system called Phytosome, insoluble botanical [active compounds] have the chance to reach the gut in the lecithin matrix with a major possibility to cross gastrointestinal epithelium.”

Bioabsorption is only the first step, she added, because the active ingredient then needs to reach the tissue where biological activity occurs. Phytosome technology allows this to happen.

Quality Control and Supply Chain Management

According to de Rensis, quality is a constant and unavoidable requirement for products, processes, technologies, services, and solutions at Indena. “We always strive to dissect, analyze, and constantly evolve our quality system, ensuring even more fairness in the system itself. As for botanical extracts, quality means the quality and control of the entire production chain, from the procurement of vegetal raw materials to checks on the finished product,” de Rensis wrote. Indena has always managed all stages of the manufacturing process in strict accordance with the most accredited protocols, she added.

Quality is particularly important now, as the industry emerges from the COVID-19 pandemic and a year of record growth, Ris noted. “The fact that new consumers are purchasing supplements, taking more responsibility for their own health during and post lockdown, is encouraging. ‘Underlying conditions’ became a classification consumers want to avoid.” Unfortunately, he added, the industry “is still plagued by products that are either adulterated or don’t meet label claims…. This has been a longstanding problem that is exacerbated when there are raw material shortages.”

Along with quality, Indena has long sought to manage its supply chain in ways that align with its circular business model. This involves full traceability, supplier qualification, and good agricultural and collection practices (GACPs).

It starts with a solid chain of custody. “One critical issue for the botanical products industry is to guarantee continuity and integrity in the supply chain together with high standard levels in terms of quality, safety, and sustainability,” Fontana wrote.

Regarding the procurement of ingredients, he added, despite the challenging times, the company’s reliable and robust partners, which have been in place for decades, have added value for Indena. Furthermore, due to its longtime experience with herbal materials, Indena is well acquainted with sourcing activities and how to maintain enough stock, which help prevent or limit shortages.

“Indena knows that paying attention at every step of the way positively impacts the quality and effectiveness we can offer,” Fontana added. “That is why we have established more than 30 quality checks, spanning the entire process, from seed to finished product, allowing us to have full traceability and complete control for a strong chain of custody.”

Environmental and Social Responsibility

The company also cares about where plants are grown, how they are handled, and the people along the supply chain, which adds another level of complexity. In fact, Bo explained, “many criteria have to be considered in a risk assessment of social and environmental impact in the supply chain.” In 2013, she said, Indena launched the Sustainable Sourcing Program to ensure the safety and wellbeing of the communities involved in its supply chain and to conserve biodiversity.

Indena also created a multidisciplinary team composed of a botanist, quality system manager, regulatory experts, a sociologist, and communications experts. This team analyzes the supply chains and their possible risk factors and then develops complex projects involving local communities, suppliers, institutions, and nongovernmental organizations (NGOs), generating positive social and environmental impacts.

Indena also has developed many programs throughout the world. Among them is the Centella asiatica Project in Madagascar.10 Established in 2015, in the Alaotra-Mangoro region of Madagascar, where most of the gotu kola (C. asiatica, Apiaceae) processed by the company is harvested, the program’s goal is to improve living conditions and decrease poverty in these local communities by promoting higher quality education and attendance rates among children, Bo explained.

Indena partnered with the Italian NGO Volontari nel Mondo RTM to help provide school kits and teaching materials to almost 3,000 children and 84 teachers in 10 elementary schools every year, organize didactic and linguistic training for teachers, build toilets and water wells or pipelines to provide clean water, and renovate and maintain school buildings.10,11

The results have been encouraging, Bo noted, improving attendance rates in participating schools to 90%, as compared to 80% in other parts of the country, increasing student enrollment by more than 10% compared to the previous year, boosting school literacy rates and exam results, and supporting teacher motivation. The project won the Convention of Pharmaceutical Ingredients (CPhI) Award for Excellence in Pharma: Corporate Social Responsibility in 2016.

The Path Ahead

Looking forward, the Indena team still sees many challenges and opportunities. Addressing authenticity of plant materials continues to be a focus, Riva wrote, as the company plans to develop and apply various techniques, including botanical, chemometric, and genetic analyses, to ensure authenticity and quality of plant materials and their derivative products.

Single- and multiple-locus DNA barcode markers, for example, are used to distinguish authentic products from counterfeits, combining standard and innovative technologies such as bCUBE® from the biotechnology company Hyris Ltd. (London, UK). Moreover, Riva noted, Indena has developed and tested an innovative DNA-based method that can strongly correlate the final product (dry extract) to the plant material used to produce it.

The need for personalized integrated solutions represents another opportunity, noted Togni. “Moving away from the ‘one-size-fits-all’ traditional concept implies having a diagnostic and tracking system and powerful algorithm to process individual data collected to elaborate personalized solutions. These [solutions] have to rely not only on drugs and supplementation, but also on dietary interventions and lifestyle changes for optimal health.”

Accordingly, the company has entered a development program with health intelligence company Onegevity (New York, NY) to further expand its commitment to innovative approaches for preventive health. “We are proud to cooperate with Onegevity,” wrote Giavini. “Our project with Onegevity is perfectly in line with Indena’s approach and with our continuous focus on research and development of highly effective solutions that are synergistic to the Onegevity wellness plan. The collaboration is allowing us to process certain botanical ingredients [in] Indena’s portfolio through the Onegevity AI platform, with the aim of discovering novel potential indications and beneficial effects for new or known botanical ingredients, as applicable to the pharmaceutical or nutraceutical market. This project fits very well with our credo ‘Science is our Nature.’”

Another increasingly important area of research is healthy aging. “Prevention and supplementation play a pivotal role in this,” Giavini added.

Whatever the future holds, Indena has never considered botanicals to be a trend and will keep looking ahead, Togni noted. “Indena’s expertise has always been creating phytochemical solutions that are versatile and timeless, evolving with people’s changing needs, with high quality, reliability, traceability, and integrity.

“The plant kingdom is still largely unexplored,” Togni added. “It expresses very high chemical diversity and complexity, developed over millions of years of evolution interacting with a surrounding challenging environment. They are very difficult to replicate synthetically. Furthermore, we see a paradigm shift in health care, moving from treatment of disease to prevention, maintenance of wellbeing, and increase of resilience.”


Indena is a long-time Sponsor Member of the American Botanical Council (ABC) and supporter of several key ABC programs. This article has been formally reviewed for accuracy by Indena staff.


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