Harmonization in process development science
In this blog, Bernd Schümmelfeder, Director-Team Leader PPD Business Development at Pfizer, explores how process development — just like creating beautiful music — relies on collaboration between all involved. With a harmonized approach, steps can be taken to shorten timelines for getting treatments to patients without jeopardizing quality and safety.
Harmonizing to meet a shared goal
In a musical masterpiece, there are many factors that intertwine to make it truly beautiful; the rhythm, the instruments, the melody and the lyrics combine perfectly because of the artists involved working together. Like making music, producing effective therapeutics relies on the collaboration of those involved to deliver something showstopping: a breakthrough treatment for patients.
Achieving the shared goal of delivering efficacious, safe and high-quality therapeutics to patients at pace requires all involved to be on the same page early on.
Formulation fundamentals
Like sound to music, formulation is fundamental in drug production. Bringing together active pharmaceutical ingredients (APIs) and excipients to form a final medicinal product relies on the harmonization of manufacturing methods and formulation, with dosage form in mind.
Throughout formulation development, constant considerations and decisions must be made, necessitating a thorough understanding of various elements, including the chosen formulation type, manufacturing processes, technology requirements and packaging materials. Of utmost importance is an understanding of API characteristics, which determines many of the decisions made throughout formulation development.
Although advancements in drug discovery techniques — including computational drug design and artificial intelligence (AI) — have expanded potential therapeutic APIs, they have also brought difficulties, particularly for oral solid drug formulation. APIs with complex structures, high molecular weights, poor water solubility and high lipophilicity are now common, leading to processability issues like sticking and poor flowability.
Overcoming these difficulties relies on a development strategy that envisages large-scale production early to identify future challenges. Even before the manufacturing process begins, collaboration from all teams is therefore needed.
Playing as an ensemble to meet purity needs
Like in an orchestra, achieving drug development and processing success relies on all involved working together as an ensemble. Without collaborative discussion between key players, manufacturers should expect issues arising from complex APIs as well as those stemming from miscommunication.
In mid-2018, the need for a collaborative approach to drug production was put in the spotlight after EU regulators became aware of nitrosamine impurities in medicines. The resulting regulatory changes necessitated pharma drug developers and manufacturers to conduct risk assessments of their commercial portfolios to determine the risk of nitrosamines forming in their medicines. By working together, development and manufacturing teams acted quickly to understand the requirements, perform the necessary risk assessments and outline mitigation strategies.
These regulatory changes highlighted an important message: developers and manufacturers must adopt a collaborative and agile approach. This approach must be capable of withstanding alterations to ensure the continued delivery of critical medicines to patients in the future.
A strategic, risk-based and collaborative approach
Drug developers and manufacturers should adopt a risk-based development approach, focusing on the factors critical to ensuring quality, safety and efficacy. This will ensure a common goal is established and difficulties are overcome proactively.
Attaining a strategic approach that is both risk-based and reliant on collaboration, like that adopted by Pfizer CentreOne, relies on three key steps.
1. Know your instrument
As with playing music, a fundamental understanding of your instrument — the API — is critical. As well as the drug load and the target product profile, the characteristics of the API will inevitably feed into the technology requirements and manufacturing process decisions for successful formulation.
Effective formulation, therefore, relies on an understanding of the API’s physicochemical properties, including the chemical core structure, stability, solubility, particle size and morphology.
2. Play as an ensemble
Co-development relies on communication and collaboration, with joint responsibility, risk management and common goals, which include:
- Maximizing speed
- Minimizing cost
- Maximizing overall value
- Delivering quality for patients
Achieving these goals requires the proactive identification of risks that could cause issues. This will rely on involving key players early, enabling strategies for mitigating attrition risks and ensuring difficulties can be overcome quickly.
3. Use the music sheet
A structured and standardized development process can guarantee all involved are working together harmoniously. It should take the form of:
- Standardized decision trees based on the established common goals — and aim to manage potential risk
- Inflection points
- Communication workflows
Decision and inflection points will take common goals into account, identifying cost management areas and prioritizing projects with a higher probability of success.
Key lessons
Through a strategic, risk-based and collaborative approach, it is possible to take calculated risks without jeopardizing quality and safety. When systems and procedures mesh with a commitment from all parties to face challenges and find solutions together, drug producers will have everything they need to make beautiful music and deliver safe, high-quality therapies to patients at pace.
To learn more about Pfizer’s approach to process development, watch Bernd Schümmelfeder’s “The Music of Process Development Science” CPHI NA presentation here.