Sustainability: exploring its significance at Angelini Pharma

WHY TO PURSUE IT

Sustainability has been a frequently mentioned concept over the last few years across many manufacturing platforms but more recently has become a popular topic within the pharmaceutical industry.

One main reason for this are the advances and impact that analytical science has had in identifying pharmaceuticals as environmental contaminants that is due to their wide use.

That is, pharmaceuticals and their residues/metabolites may enter surface waters via wastewater treatment plants (WWTPs) after human use (domestic and hospitals) or enter soils if sewage sludge produced during wastewater treatment is applied to agricultural land and of course emissions from API production processes may include active pharmaceutical ingredients, but also potentially harmful solvents, or byproducts of the production process.

WHAT ANGELINI PHARMA IS DOING

As a follow up to our publication in this same journal last fall focusing on “green chemistry” and its impact on production costs, here we will focus on the topic of sustainability and specifically its impact on effluent reduction and what Angelini Pharma is doing in this regard.

academia whose set of objectives was to develop alternate production options that would focus on new processes for existing products that would ultimately substantially reduce the negative environmental impact while at the same time providing an acceptable ROI.

The “mantra” of our consortium termed “ETERNAL” is “to bring together academia and technology institutes, the private sector, civil society participation and pathways to policy, in an effective multi-stakeholder approach, whereby each stakeholder is complimentary and mutually responsive to each other in addressing the complex development challenges and catalyzing an enduring Green Pharmaceuticals movement that will have a high impact on the environment. Key to ensuring the success and endurance of a multi-stakeholder approach is the ability to obtain a collective-impact approach, where each party has its return of investment aligned with a shared mission.” Within Angelini Pharma this exercise includes the participation of 2 our small molecule API manufacturing plant in Aprilia and our R&D lab in Ancona dedicated to formulation development, both sites in Italy.

HOW WE PURSUE THIS TARGET

Specifically, the Ancona case study involves the potential feasibility of producing a solid dosage form of one of our blockbuster medicinal products through an emerging machinery suitable for continuous In September of 2022 Angelini Pharma became part of a consortium consisting of 15 other EU companies and manufacturing. Examples of the main benefits of this “new“ technology would be (but not limited to):

• shorter processing times
• smaller facilities
• reduction/elimination of water
• simplified formulation recipe (less raw
• materials)
• improvement of fundamental properties
• of drug and finished medicinal product
• real-time monitoring using PAT tools

At Aprilia we are investigating a more efficient use of solvents (increased quantity and quality of recycled solvents) in the manufacturing process to produce one of our major API (several hundred MT annually). Specifically, our goals are to:

• Increase the amount of isobutyl alcohol recycled and reused in the production process (from 50% to 85%, which corresponds to a total amount of recycled solvent of about 1.000 tons/y tons)
• Increase the amount of acetone, recycled & reused in the production process (from 80% to 95% which correspond of a total amount of recycled solvent of about 1.800 tons/y).
• Future replacement of 100% of current actual solvents (acetone and Isobutyl alcohol) by greener (e.g. Ethylene lactate, methyl acetate et) options or biobased solvents.
• Capture impurities and unreacted formulation components during production and in waste products.

FUTURE OF THE PROJECT

Ultimately the goal for Angelini Pharma as well as our external partners is to provide scalable, validated, ‘safe-by-design’, ‘green-by-design’ and ‘compliant-by design’ innovative processes for green pharmaceutical manufacture (and that are also less environmentally harmful during use and disposal). For Angelini Pharma, the objectives are the potential implementation of a continuous manufacturing technology; Discontinuous Synthesis (batch reaction) using recycled Isobutyl and acetone and/ or substitution by greener or biobased alternatives.

Of course, changes in already validated pharmaceutical production processes always have a regulatory impact that needs to be navigated and all the “stakeholders” are sensitive to this issue, but ultimately the goal is that the manufacturer and regulatory organizations will be aligned.

Our group has been 18 months into the exercise (of a 4-year plan) and the results so far are very encouraging. The stakeholders will have a meeting at the Angelini Pharma Headquarters in Rome in March to review our progress and update our “plans”.

So, for Angelini Pharma “SUSTAINABILITY” is not just a “theoretical concept” but a culture being developed across many of our internal platforms.

This project has received funding from the European Union’s Horizon Europe Framework Programme (HORIZON) under grant agreement No 101057668.

Link: eternalproject.eu/