Doppel perspective on Orphan drugs

According to the US Food and Drug Administration (FDA), an orphan drug is defined as one “intended for the treatment, prevention or diagnosis of a rare disease or condition, which is one that affects less than 200,000 people in the US” (which equates to approximately 6 cases per 10,000 of its population), “or meets cost recovery provisions of the act”.  In the European Union (EU), the European Medicines Agency (EMA) defines a drug as “orphan” if it is intended for the diagnosis, prevention, or treatment of a life-threatening or chronically and seriously debilitating condition affecting not more than 5 in 10,000 EU people. EMA also qualifies a drug as orphan if, without incentives, it would be unlikely that marketing the drug in the EU would generate sufficient benefit for the affected people and for the drug manufacturer to justify the investment.

In the short interview below, Rocco Paracchini, Chief Commercial Officer, and Salvatore Agostino Giammillari, R&D Director at Doppel Pharma CDMO, discuss Doppel’s perspective.


Rocco, can you comment on what Doppel’s perspective is and its commitment to orphan drugs?


R: Thanks to the advancements in medicine in the diagnostic fields, a growing number of people every day is newly diagnosed with a rare disease. At Doppel, although we are a B2B organization, we have decided to keep an eye where others don’t. In the last few years, our R&D worked with its partners on several development programs around Orphan Drugs to the point we have decided to dedicate an area of our Milan based facility (Rozzano) to the production of Orphan Drugs. The area has been inspected and approved by AIFA/EMA and FDA.

This decision marks a sign of Doppel’s commitment to our partners and customers worldwide, to ensure that every patient gets the attention and treatment options they deserve.


Salvatore, expanding on geographies: what markets can Doppel serve today?


S: In 2004, among the earliest in Italy, we were inspected and authorized by Italian Health Regulatory Agency (AIFA) for the production of small-scale batches for clinical use. Thanks to this authorization, Doppel can manage the entire process (formulation, production, control, packaging, stability studies, shipping, and completion of the necessary documentation) up to clinical trial supply, even in small series, for the whole European market.


In 2019 Doppel Pharma CDMO obtained an US FDA approval without form 483 for an orphan drug in capsule. The drug product was developed by R&D as a generic of a marketed specialty and transferred to commercial manufacturing for the market. The developed product shows a plus compared to reference in terms of stability and storage conditions because the specific formulation that we developed stabilizes the API and prevents the need to adopt cold chain logistics. This formulation is subject to Patent Application, seeing Doppel R&D team as inventors.


Salvatore, guide us through the formulation development of an orphan drug


S: R&D Doppel offers its knowledge and experience in orphan drug for:


  • Smart development with the best optimization between performing several formulation trials with a small amount of APIin a non GMP area
  • Technology to adapt the different dosage strengths to patient compliance and acceptance
  • Flexible equipment for small batch size.
  • Once ideal pharmaceutical formulation has been identified, moving the GMP area (reproducibility guaranteed, same equipment and same personnel).
  • Purchase of excipients from certified suppliers according to customers’ requirements.
  • Chemical and microbiological testing of raw materials according to current pharmacopoeias (EP, USP, etc.).
  • Development of the most appropriate analytical methods and their evaluation, according to the defined pharmaceutical formulation.
  • Pilot-scale production required for product development and stability testing.
  • Consolidated experience in NDA submission.
  • Stability studies, considering the customer’s market climatic conditions (Stability Zones).
  • Detailed production records for each batch available to customer upon request.
  • Competitive lead times and immediate response to extra orders.
  • Flexible and on time delivery.


Rocco, what future plans Doppel Pharma CDMO has in mind in the Orphan Drug fields?

R: In the last 5 years Doppel Pharma CDMO has improved its experience in orphan drug development and submission of NDA and IMPD. Nowadays, we are already manufacturing a generic drug product for Europe; this product has been recently approved by USFDA and has just been launched in the American market. Another drug, already commercialized in Europe, is in the process of being approved in certain South American countries. In parallel, we are working to support two other imminent submissions to USFDA, in 2023.

We anticipate that all these activities will continue in the upcoming months thanks to the acquisition of new projects, as we expect to receive increasingly more inquiries by established and new customers all around the world. I am not aware of many other CDMOs out there that can claim to have a fully dedicated “Orphan Area” in their facility, as Doppel does. So, it goes without saying, we will maintain the commitment towards enabling more and more orphan drugs to be developed and commercialized by our business partners, to ensure that no patient is left without a treatment option.