Industry Insights with… Stephen Byard

 

Welcome to our Industry Insights series, where we provide a platform for our scientists to share their extensive knowledge of subjects within pharmaceutical development. In the first blog of this series, we are taking a look at the advantages of adaptive capsule manufacturing.

As the quest for shorter development timelines continues, an innovative approach to the manufacture of clinical products is required. Our Head of Molecule Development & Scientific Direction, Dr Stephen Byard, examines how capsule manufacturing can be employed to reduce the time to clinic.

 

What are the main differences between capsule and tablet manufacturing?

The main difference between capsule and tablet manufacturing is that capsules can be manufactured using an adaptive process which is suitable for early phase human trials. Tablet manufacturing on the other hand, tends to require more up-front development and is geared towards Phase III clinical trials and commercial products. 

What is the key advantage of choosing capsules for Phase I - why is this a good route for early clinical trials?

A key advantage of capsule manufacturing for early trials is that you can introduce the drug substance without blending with excipients, circumventing the need for extended stability studies. The manufacture of drug substance-in-capsule can therefore be conducted without any in-depth compatibility studies. This significantly accelerates initiation of clinical trials, providing economic advantages with no compromise in quality and a reduced time to market. Frequently, the adopted approach can also be seamlessly continued for Phase II trials, in parallel with more in-depth formulation development work to prepare for subsequent clinical studies or in readiness for commercialisation.

How is capsule manufacturing transforming the pharmaceutical industry?

There are different approaches to capsule manufacturing that can be taken during drug development. A conventional approach is to blend drug substance with excipients and subsequently fill capsules with the blended product. At Arcinova, we are engaging with clinics to supply capsules containing drug substance alone. This allows us to manufacture a relatively high number of capsules in a short period of time, with reduced lead time to the clinic circumventing the need for stability studies that are required when a drug substance is blended with excipients. Adaptive capsule manufacturing is a tried and tested approach that is being adopted by an increasing number of clients.

How will this impact the future of the industry/healthcare?

Adaptive capsule manufacturing is particularly transforming clinical trial work prior to commercialisation, including Phase I, Phase II, and human absorption, metabolism and excretion (AME) studies. The main impact of a drug substance-in-capsule approach is that it helps progress drugs to market more quickly. Patients benefit from this accelerated route to market.

Are there any new capsule manufacturing technologies that are having an impact on the industry?

The application of semi-automated equipment for capsule manufacturing is having a significant impact on the industry. One of the advantages of this instrumentation is that it measures the mass of each individual unit produced. You can therefore be 100% confident that what goes to the clinic really is within specification. Efficiency is increased through the use of semi-automated capsule manufacturing equipment because it removes the need for combining capsule content and any follow up with further analysis. Arcinova currently has two different types of instrumentation that are used for capsule manufacturing. We have also significantly invested in technology to increase throughput and implement some degree of additional containment to protect operators during capsule filling.

What factors should be considered in the decision-making process when choosing capsules over tablets?

It is important to ensure the drug substance is suitable for this adaptive capsule manufacture approach by analysing how the drug substance disperses in biorelevant media. This involves employing state-of-the-art physical and molecular characterisation equipment to gain a full understanding of drug substance properties and to determine what will happen when applying a powder-in-capsule approach.

At Arcinova, we carefully consider the physical and chemical properties of the drug substance, in conjunction with its behaviour in biorelevant media, to ensure a capsule manufacturing approach is valid for the intended purpose.

 

If you would like to find out more about capsule manufacturing and the work of our Formulation Development team, please get in touch here