Supporting Customers with an Integrated Fermentation Offering

Demand for microbial fermentation services is increasing, but there are few contract manufacturers with an intense focus and expertise in this important bioprocessing technology. Olon S.p.A. offers truly integrated fermentation process development and manufacturing capabilities, including downstream chemical modification, purification and spray drying.

Growing Interest in Microbial Fermentation

Demand for microbial fermentation services is increasing as pharmaceutical manufacturers realize the economic benefits of producing many types of bioactive molecules using this technology. One market research firm estimates the overall value of the market for chemicals produced by fermentation was $58.68 billion in 2018, with pharmaceutical products accounting for approximately 20% of the market,1 while another pegs the value of the market for microbial-produced biopharmaceuticals at $100 billion in 2017 and expanding at a CAGR of 6%.2 The contract pharmaceutical fermentation services market is predicted to expand at a similar rate of 5.9% through 2026, reaching a value greater than $4.0 billion.3

For the production of many smaller biologics, microbial fermentation can have cost and time advantages over mammalian cell culture, providing shorter development timelines and reduced variability. Commonly used Chinese hamster ovary cells are not able to practically and economically produce some biomolecules currently of interest, such as single-domain antibodies and peptibodies.

Using fermentation for the manufacture of longer-chain peptides (30–40 amino acids) is economically advantageous compared with traditional solid-state chemical synthesis. In 2018, more than 100 peptide therapeutics were available globally, with over 100 additional peptides in late-stage clinical development and more than 200 at the preclinical stage.4 The increasing interest in peptide therapeutics is a key driver of growth for the pharmaceutical fermentation market.

Microbial fermentation provides a sustainable alternative for the production of natural products (with limited natural availability) and therapeutic peptides. Leveraging microbial fermentation can allow reduction of the use of limited natural resources, producing purer products and reducing the environment impact.

Expanding Fermentation Expertise and Capacity

Olon is a world-leading advanced intermediates, proteins, enzymes, peptides and small molecule active pharmaceutical ingredient (API) contract development and manufacturing organization (CDMO) and generics supplier, with headquarters in Italy and manufacturing sites around the world.

It has been the strategic plan of the company to build an integrated offering through a combination of acquisitions and organic growth. Our first step was taken in 2016, when we purchased Italian API producer Infa Group (2 manufacturing sites in Italy and 1 in Spain). That move was followed by the acquisition of the Chemical Division of U.S. CDMO/contract research organization (CRO) Ricerca Biosciences, which added new early-phase CDMO capabilities and expertise while providing additional access to the American market.

Continuing the expansion of our global footprint, in 2018, we acquired from Sandoz-Novartis a microbial fermentation and chemical synthesis API manufacturing facility in Mahad, India. That purchase was followed by the acquisition of Capua BioServices S.p.A., one of the larger provider of beta-lactam–free fermentation services in the world, in early 2019. We have already initiated construction of a new GMP manufacturing plant for the manufacture of multiple products up to commercial scale at this site. Having finalized our 3-year development plan, we are now evaluating opportunities to formally enter the biopharmaceutical market.

Olon has a breadth of capabilities for API manufacturing. The acquisition of Capua Bioservices has expanded not only our fermentation capacity, but our knowledge and expertise in the development of efficient, cost-effective fermentation processes.

We have a total fermentation capacity of 4.500 m³, based on 65 fermenters spread between two manufacturing locations in Italy, and an additional 400 m³ in fermentation capacity at our site in India. We offer dedicated solutions for peptides, proteins, enzymes and specialty small molecules for clients in Europe as well as the United States, using a variety of microbes, including, but not limited to, yeast (Saccharomyces cerevisiae, Pichia pastoris), bacteria (Escherichia coli, Bacillus, Streptomyces) and fungi (Aspergillus, Trichoderma).

Integrated Services

Olon’s pharmaceutical services, including fermentation, are managed by a dedicated commercial team, while a separate commercial team handles the non-pharma business, named Food+ (food, feed and additives). We have dedicated manufacturing areas and equipment for pharmaceutical products (including HPC), and our sites operate according to cGMP guidelines and are annually audited by the U.S. FDA, the EMA and other global regulatory authorities.

Our involvement in the food industry is key differentiator for Olon. We have experience implementing quality systems and manufacturing products according to both GMP guidelines and food manufacturing regulations. As a result, we are highly flexible and can provide support – and unique solutions – to producers of products that fall into the gray area between food and pharma.

Our extensive experience in microbial fermentation is combined with the highly flexible design of our process development lab, pilot plant and commercial manufacturing units. We are able to implement different processes and different types of unit operations and even multiple processes in parallel. Based on the experience gained in the last years, we have also increased our flexibility in how we support our customers.

Olon’s highly experienced R&D team delivers solutions to critical and complex projects at each development phase, from familiarization and proof of concept to robust commercial-scale production. We have strong expertise in strain development/improvement and the optimization of fermentation and downstream processes, including purification and chemical modification. Our ability to provide fermentation and chemical modification within one company provides tremendous value for our customers by eliminating the need for technology transfer.

The acquisition of Capua also provided access to state-of-the-art spray-drying capabilities within a facility opened in 2018. With this technology, Olon is able to offer customers an economically attractive alternative to lyophilization, crystallization and micronization. Spray drying allows the production of stable formulations of dry powder proteins, peptides, monoclonal antibodies and can often enhance the bioavailability of poorly soluble compounds. It also enables precise engineering of particle size and the embedding of microencapsulation technology.

Five Strong Pillars

The CDMO Division of the Olon Group has implemented a Five Strong Pillars approach to ensure that we consistently meet or exceed our customers’ expectations. The Pillars include quality on time in full (QOTIF), supporting customers from R&D to commercial, a strong team-based project management culture, security of project information and cost management.

Underlying and supporting all of our development and manufacturing activities is our financial stability and commitment to be a long-term partner for our customers. We are interested in being strategic partners with our customers and are committed to forming long-term, risk-sharing, win–win relationships. Customers also know that we maintain the confidentiality of each project without compromise.

Our pharma-focused commercial team is backed by an excellent group of highly experienced scientists, project managers and engineers. These talented people make up our dedicated project teams, which follow each project from the day they are introduced to Olon until they are completed and we have met all customer expectations. This approach fosters excellent communication and the building of strong relationships.

References

  1. Fermentation Chemicals Market Size, Share & Trends Analysis Report By Product (Alcohols, Enzymes), By Application (Industrial, Plastic, Pharmaceutical), By Region, And Segment Forecasts, 2019 – 2025. Rep. Grand View Research. Apr. 2019. Web.
  2. Biopharmaceutical Fermentation Systems Market to be Worth US$ 17.8 Billion by 2026, Says TMR. Transparency Market Research. 19 Jul. 2018. Web.
  3. Jha, Shambhu Nath. “Growing Usage of Fermentation Techniques for Developing Active Pharmaceutical Ingredients expected to drive the Revenue Growth of the Contract Pharmaceutical Fermentation Services Market over 2018–2026. The Guardian Tribune. 15 Mar. 2019. Web.
  4. Global Peptide Therapeutics Market, Dosage, Price & Clinical Trials Insight 2024 - 101 Marketed Drugs with a $50 Billion Opportunity. Research and Markets. 6 Sep. 2018. Web.

Giovanni Celeste

Giovanni Celeste is the Senior Vice President of Sales & Marketing of Olon Group. He has more than 20 years experience in the pharmaceutical industry and healthcare business. He joined Olon in 2004 in the Sales & Marketing Dept. and has continued to contribute to the company’s strong internal growth. He currently supervises the global commercial activities of the Group for both CDMO and Generics. Prior to Olon, Mr. Celeste served in other Italian APIs manufacture, Dipharma, as Area Manager. Mr. Celeste holds a Master Degree in Economics from the University of Pisa, Italy.