FOCUS: Formulation Development
What type of formulation work is increasingly outsourced?
Historically, new active ingredients were targeted to oral tablets or vialed small volume parenterals. Additional delivery routes were typically investigated for life-cycle management. This approach was well-suited to development of active ingredients selected by rapid animal model screening for efficacy against a range of diseases.
As knowledge of biochemical pathways has increased, active ingredient development has evolved into beginning with a hypothesis of a new therapeutic biochemical pathway. Using rapid throughput screening, molecules are selected to target that specific pathway. The most important step is demonstrating the viability of the therapeutic rationale and less important is having a molecule with optimized stability, solubility, bioavailability or activity. A more robust molecule can be later designed incorporating knowledge learned from the first active ingredient.
Formulation development for novel dosage forms or delivery routes has become a first-line option for commercialization. The core competency for these novel approaches frequently resides in contract formulation developers.
Discuss how outsourcing formulation development ultimately accelerates overall drug development.
From personal experience, working at an innovator company, the number of molecules a given scientist might work with averages from 1 to 2 per year. A scientist working in a contract development environment might average three or more times that number.
In an innovator company, molecules arrive and are progressed in order through a series of development steps. The importance of the decisions made in each step may not become clear until reaching the next step. In a contract environment, however, formulation scientists are often involved with active ingredients, many at a different stage within a short period of time. This provides a greater source of recent and relevant experiences to draw from in problem solving. The impact of something as simple as observing the result of an exotherm during mixing at large scale on one given day becomes an experience that scientists may integrate in formulation screening on the next day.
Formulation development training is accelerated in a contract environment because teaching and learning experiences are not separated by large amounts of time. Training leads to fewer mistakes, avoiding the need for reformulation, project delays, and cost overruns.
Small and large pharma decide to outsource formulation development for different reasons. Discuss some of these contrasting key drivers.
Typically companies of a smaller size can only afford to pursue 1-3 molecules for 3-4 indications. After successfully developing the formulation, the burden shifts from the development group more to Operations, Engineering, and QA. Maintaining a formulation group with enough people for critical mass becomes a substantial overhead expense. The alternative approach, to rely on one or two people for formulation development, greatly limits the range of experiences available to solve challenging formulation development issues.
Therefore, it becomes a more cost effective approach for small pharma to outsource the formulation development, gaining the experience of a large number of formulators and eliminating the need to reduce formulation staff in the future.
For large pharma, enough molecules are typically in development to continuously derive value from a formulation development group of critical mass. Large pharma might choose to outsource formulation development to evaluate a unique dosage form, dosage size, or delivery route or for potent compound containment. In this case, the benefits include: obtaining a second-look at formulation development of a challenging molecule and the ability to temporarily access a deep niche experience set that would take too long to cultivate internally.
How do contract companies differentiate themselves in this competitive market?
The greatest factor in differentiation is institutional knowledge. Experience creates scaled benefits around all aspects of formulation development:
Businesses are comprised of materials, equipment and people who have used them both to meet a previous goal. Institutional knowledge is paramount in understanding the next right step to keep a project moving forward.
Discuss the importance of communication in formulation development partnerships.
A basic training module for implementing ICH guidelines Q8, Q9, and Q10 states the main message of the new quality paradigm: “Science is no longer isolated; it is living across the lifecycle of the product/process within a Quality Management System.” This philosophy is manifest in the Product Development report that comprises section 3.2.P.2 of the COMMON Technical Document. This report can reach as far back as initial formulation development to justify control strategies.
The science behind the drug product development is now open to full scrutiny.
The best time to evaluate work is before it is done. The Quality-by-Design process includes formulating hypotheses, anticipating responses to a range of outcomes, and then performing experiments. The time for customer/contractor communication is not only at the point of sending results but during the planning stages.
Taking the time to define a plan incorporates all the learned experiences on the team. Planning allows full incorporation of the customer’s knowledge base behind API sourcing, manufacture, and synthesis. Additionally, taking time to communicate a plan facilitates more timely review of original project scope, reducing cost overruns, and preventing erosion of confidence between customer and contractor.
Any closing thoughts?
Combined populations of China and India represent over one-third of the people on the planet. Due to a societal change, consumerism is increasing. China is projected to have greater than 15% pharmaceutical market size growth through 2020. Due to differences in factors as simple as climate, one might expect that even common diseases differ from those found in Europe and North America.
New pharmaceutical products are presumably developed to meet local needs and preferences. As capacity is built to create products for their local markets, performing formulation development for international markets presents a business opportunity for both customers and contractors.