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Internationalization of a European CDMO

Internationalization of a European CDMO

Oct 28, 2019PAP-Q3-19-CL-010

Doppel is a leading Italian, finished dose contract development and manufacturing organization (CDMO) with aggressive plans for expanding its presence in international markets. Backed by a private equity firm with a strategic outlook, the company has been investing in new capabilities and capacities designed to meet the evolving needs of its customers. Recent U.S. Food and Drug Administration (FDA) approval of solid oral dose manufacturing at our Rozzano facility in Milan, Italy is just one of many steps the firm is taking to internationalize its business.

25 Years of Experience in Finished Dosage Form Development and Manufacturing

Doppel was established in Italy in 1994 and over the last 25 years has become a leading European CDMO offering a range of clinical and commercial finished dosage form manufacturing and packaging services for our worldwide clients.

With highly advanced research and development labs and pilot-scale facilities, Doppel provides customized product and formulation development services for over-the-counter (OTC), generic and branded drug products ranging from pre-formulation to industrial-scale production, including manufacturing of investigational new drug/investigational medicinal product (IND/IMP batches), clinical labeling, regulatory support and common technical document/drug master file (CTD/DMF) drafting services. We currently manufacture more than 1000 SKUs, including non-sterile and sterile (injectable) liquid, semisolid, capsule, tablet and other oral solid dosage forms, and have supported the registration of more than 50 pharmaceutical products. We also possess the facilities and capabilities to work with highly potent actives and formulations.

Excluding multinational firms, Doppel is one of the largest CDMOs in Italy. Even so, we pride ourselves on the agility and responsiveness we offer and the close relationships that we develop with our clients. We have a strong track record in building and forging close partnerships and providing high-quality services tailored to the specific needs of each individual customer at all stages, from formulation, development and manufacturing all the way to marketing and post-marketing controls. All of these attributes have earned us the business of more than 100 clients, including leading multinational branded and generic pharmaceutical companies.

Doppel is a CDMO that emphasizes development. We strive to deliver the best service possible and support our clients with the extensive expertise we have gained in new product and formulation development. We are focused on developing novel and optimized solutions for our customers and doing so in the shortest time possible and at a fair price. Those products can then be produced at commercial scale with the highest degree of reliability.

Our development and manufacturing activities take place at two state-of-the-art facilities located in Italy. The Rozzano plant in Milan was acquired in 2001 from Pfizer, while the Cortemaggiore facility in Piacenza was constructed by Doppel in 2004. The closely integrated and synergistic capabilities and capacities at both sites guarantee business continuity and on-time-in-full (OTIF) service delivery.

Semisolids, Liquids, Soft-Gel Capsules and Highly Potent Tablets

Doppel’s Cortemaggiore plant covers an area of approximately 44,000 m2 and employs more than 260 people with extensive experience in the development, manufacture and packaging of semisolid and liquid finished pharmaceutical products and medical devices.

Small-volume (drinkable liquids, drops, topical sprays, nail lacquers and throat sprays) and large-volume (syrups, mouthwashes, vaginal solutions, oral suspensions and topical solutions) liquids are produced in glass and plastic vials and bottles. Semisolids include creams, ointments, gels and steriles (terminal sterilization). Suppositories, ovules and soft gelatin capsules are also produced at the plant. Highly potent drugs in tablet form are manufactured in a separate, independent building designed with the facility controls and equipment necessary to effectively achieve high containment.

Doppel Cortemaggiore has been inspected and approved by AIFA, Korea KFDA, ANVISA and the Ministry of Health of Kenya Republic and is certified to manufacture both investigational and commercial medicinal products.

The site is also certified according to the environmental and safety management systems ISO 14001 and OHSAS 18001 and according to ISO 13485 for the manufacture of medical devices.

Over the last four years, nearly $45 million has been invested in facilities, equipment and capabilities at Doppel’s two manufacturing sites.

Non-Sterile Liquids, Solid Dosage Forms and Injectable Products

The Rozzano plant covers an area of approximately 25,000 m2 and employs more than 260 staff with expertise in the development, manufacture and packaging of non-sterile liquids, solid dosage forms and injectable products.

Solid dosage forms include tablets, mini- and micro-tablets and granules. In addition to uncoated tablets, we manufacture film-coated single and multilayer tablets that can be formulated as immediate- or sustained-release dosage forms. Uncoated and coated mini- and micro-tablets can be filled into hard gelatin capsules. Granules are produced using conventional technologies and can be filled into sachets, hard gelatin capsules and tank caps or be compressed into tablets.

Sterile ampoules are manufactured using either aseptic processing systems or via terminal sterilization.

Doppel Rozzano has been inspected and approved by AIFA, China FDA and Ministry of Health of Kenya Republic; and is certified to manufacture both investigational and commercial medicinal products. The site is also certified according to the environmental and safety management systems ISO 14001 and OHSAS 18001.

Our R&D division is currently developing an internal pipeline of innovative products based on our patented technology platform for chronotherapeutic target delivery.

Focused on Targeted Delivery for Oral Solid Dosage Forms

Within Doppel, our applied research services include analytical development studies, formulation development, stability studies (ICH), process development, scale-up, process validation, regulatory affairs, technology transfer, life cycle management support, CTD documentation and product manufacturing and labeling for clinical trials.

The R&D Division, which is hosted at the Rozzano site and include pilot facilities approved by AIFA, also develops a range of highly innovative formulation technologies, including sustained- and controlled-release oral solid dosage forms with various release profiles, including site-specific delayed-release delivery; multi-layered tablets possessing combinations of release profiles of the same or different drugs in a single tablet; multi-particulate systems, such as granules or micro-tablets containing different dosages and release profiles, filled in a single capsule; bioavailability enhancement drug delivery systems for increasing permeability or solubility of active drugs; and innovative delivery systems containing solids and liquids in one dosage form.

These capabilities provide added value for our customers by offering novel approaches for the targeted delivery of active pharmaceutical ingredients (APIs) and can be applied to both new chemical entities and generic products. Targeted delivery ensures the release of the right quantity of API at the correct site of action. The end result is safer and more effective drugs and the potential for lower-dose formulations.

Our R&D division is currently developing an internal pipeline of innovative products based on our patented technology platform for chronotherapeutic target delivery. This technological platform is a modified controlled-release pharmaceutical composition that has been developed with the aim of the delivering drug substances into the gastrointestinal tract by combining both pH-dependent and pH-independent polymers applied on multiparticulate and/or multilayer solid dosage forms. We are proud to note that the first drug candidate has been successfully submitted to a phase I clinical trial, and we expect to conduct more phase I/II clinical trials in 2020 with other molecules from this pipeline.

For our customers, using our established formulation platforms reduces the effort and time required to develop novel formulations, saving them money and accelerating their development programs. They also enable customers to meet increasing expectations from regulatory authorities for patient-centric formulations, achieve product differentiation and establish a competitive advantage. For existing drugs, they also provide a means to extend patent life and create opportunities to address new indications and new patient populations. Patients benefit from greater convenience and ease of use, which often leads to increased medication compliance and better outcomes.

Backed by Private Equity with a Clear Vision for Growth

Since 2015, Doppel has been part of the private equity firm Trilantic Europe, which holds 100% of the shares. Trilantic Europe is focused on control and co-control investments in Western Europe, using flexible transaction structures, partnering with family-owned businesses and providing growth capital to outstanding management teams.

We are grateful that Trilantic Europe has more than just financial objectives for their investment in Doppel and has established a clear vision for our growth. Indeed, Doppel is viewed as a strong base in the CDMO industry that can be built upon through organic growth, investment in greenfield facilities and the acquisition of other CDMO businesses.

Most importantly, Trilantic Europe has been willing to invest significantly in Doppel to enhance and expand our capabilities. In fact, we have substantial investment plans and strategies for growth in terms of size and presence across diverse geographic regions. In particular, we intend to strengthen our research and development, achieve strategic growth through the acquisition of niche capabilities and increase Doppel’s presence in international markets, such as the United States and the Far East.

Investing for the Future

Over the last four years, nearly $45 million has been invested in facilities, equipment and capabilities at Doppel’s two manufacturing sites. Major investments have included the installation of an innovative sterile gel production plant, increasing our capacity to produce hormonal and other highly potent drugs and expansion of our soft-gel capsule manufacturing capacity.

Investments have also been directed at upgrading or replacing older equipment to increase efficiency and productivity.

Doppel has also adopted an aggressive plan to improve the sustainability of our manufacturing operations. We are currently in the midst of an ongoing process to harmonize both production sites and put into place various systems designed to decrease our energy consumption and reduce the CO2 emissions from our facilities. We intend to educate the company in this way in order to attain a high greenfield facility level, with state-of-the-art equipment and technologies.

Doppel is a CDMO that emphasizes development.

Going forward, Doppel is focused on expanding our capability for the production of sterile injectables, including vial fill. The percentage of biologic drugs in the pharmaceutical pipeline continues to increase, and we feel Doppel cannot exclude establishing a foothold in this technology to stay current and relevant in the future.

With respect to external investments, Doppel is evaluating potential acquisition targets that will fit with our existing business and vision for growth. Appropriate targets are being considered in all locations with well-developed and capable manufacturing industries, including but not limited to other European countries, the United Kingdom, the United States and Canada.

Increasing International Presence

When Doppel was founded in the early 1990s, our focus was on serving smaller generic producers within the domestic Italian pharmaceutical industry. Over the last five to six years, we have focused on expanding our customer base to include small and large OTC, generic and branded pharmaceutical manufacturers with operations around the globe. Today we supply more than 100 customers all over the world, including many international big pharma companies.

Our international reach is now expanding to the United States as well. In April 2019, the Doppel Rozzano Plant was inspected by the U.S. FDA, with a 0 (zero) 483 form being issued for dispensing, bulk preparation (mixing), bulk finishing (encapsulation), primary packaging (bottles) and secondary packaging in cardboard boxes for oral solid dosage forms (capsules), including serialization capabilities. We plan to follow up on the approval for this area with expansion to the remaining areas of the Rozzano Plant and Doppel Cortemaggiore.

At the same time, Doppel has an initiative in place to reduce internal complexity and improve the efficiency of our manufacturing lines by significantly selecting the critical mass of customers. By the first quarter of 2020, we will have created a proactive loop targeted at reducing our internal costs. The gains we achieve will be shared with our partners, thereby enabling us to be more competitive.