Activities in pharmaceutical development – Finding the balance. What to do when?

Activities in pharmaceutical development – Finding the balance. What to do when?

Pharmaceutical development comprises the early-stage development on laboratory scale through late-stage development on commercial manufacturing scale, including the Process Performance Qualification (PPQ) batches as the final step before commercial manufacturing. Pharmaceutical development of a new product consists of extensive activities which requires many years and significant investments. Throughout the different stages of development decisions must be made, and there is no “one-size-fits-all” escape. The end goal, the requirements to file for market authorization, must be well-defined. Various milestones are linked to each development stage. Nevertheless, strategies for development can vary between products and companies depending on the type of product and experience with similar products or manufacturing processes. 

For most development activities it is known when they have to be completed (e.g. for IND/IMPD submission) which is often the best time to perform them. However, throughout the pharmaceutical development it might be beneficial to have process and product knowledge earlier then strictly required to support the decision-making process later on. It is vital to see the big picture, identify the risks and knowledge gaps and determine when to close them. ICH Guidelines Q8, Q9 and Q10 can help to create and properly document an overview.

Decisions made in the early stages of pharmaceutical development can have an impact on the execution, planning and risks of development and qualification studies later on. Increased product and process understanding by performing characterization and/or range finding studies at the early stage of process development can help in the decision process in consecutive steps, such as the final process design or choice of manufacturing equipment. Studies in early development are typically flexible to execute, and in case of an unexpected result, the impact on the program is low and there are possibilities to make adjustments. If an unexpected result is determined later on in the program, it is difficult to make changes and there is hardly time to implement the change, potentially leading to delays in the program (worst case: repeat of clinical studies). Another big advantage of performing studies early is that they can be leveraged into later stages when properly executed and reported. This will reduce the complexity and workload of, for example, PPQ batches.

However, there might be a future change, unknown at the time the study was performed, making the study less representative for the commercial process. This can result in the (partially) repeat of a study. On the other hand, an intensified product and process characterization at early stage could potentially lead to delays of (first in human) studies. In that case, a well-planned and well-managed parallel development and clinical program can ensure that timelines are met.

To summarize, it is important to continuously question how a study result can contribute to a robust and efficient pharmaceutical development, and at what cost and risk. Furthermore, it must be known when certain data is needed to support regulatory submissions. Those insights can be very beneficial for the overall pharmaceutical development planning, costs and risks in later stages.

 

 

Perform early

Perform late

Advantages

– Can provide valuable information for decision making.
– Can reduce workload, complexity and risk in later stages (e.g PPQ).

– Most likely to be 100% representative for the commercial manufacturing.

Disadvantages

– Investments earlier in the program.
– Risk for delay in clinical studies.

– Big impact if study fails or results are unexpected.

Risks

– Study may have to be repeated if the process changes.

 

Do you want to know how we can help you. Read about our expertise and services on the proces development page

43-Geert-van-Liempt-Progress-PME

Geert van Liempt

Senior Consultant
g.van.liempt@progress-pme.nl