Market demands, trends impacting APIs and excipients: MilliporeSigma

As the drug market and associated demands evolve, so do the active pharmaceutical ingredients (APIs) used to make them, as well as the excipients. To learn more about these ever-changing factors and how to plan ahead, Outsourcing-Pharma connected with Thomas Briel, strategic marketing manager of excipients liquid application for MilliporeSigma, the US and Canada life science business of Merck KGaA, Darmstadt, Germany.

OSP: Can you share what sorts of formulation challenges and other issues you’ve encountered with customers?​

TB: The most efficacious APIs are not always the simplest candidates to formulate in terms of solubility, bioavailability, and stability. Therefore, these are key focus areas for our customers.

Development of new active pharmaceutical ingredients (APIs) is lengthy and cost-intensive, thus avoiding any potential risk that may limit the product’s success is of utmost importance. Today, many APIs are not being commercialized as they are poorly water soluble, exhibit less stability, or become too viscous at higher concentrations.

Rather than going back and redesigning the API itself, all those challenges can be addressed by a tailored and advanced formulation, paired with high-quality excipients. Our comprehensive portfolio includes stabilizing excipients to help avoid aggregation and chemical degradation of proteins, as well as a variety of excipients to increase solubility and bioavailability of both large and small molecule APIs.

OSP: Based on the conversations and market conditions coming out in recent months, what should the industry expect in terms of API trends?​

TB: As APIs become more complex, as a result, they will also become less soluble, less stable, and more sensitive to temperatures and/or physical stress. Therefore, there will be an increasing need to find tailored solutions to overcome these challenges.

We also expect to see a continuous focus on patient convenience and quality of life, with treatments that require less frequent dosing and have minimal side effects. Additionally, we expect to see a continued trend towards more personalized medicine through innovations like 3D printing.

OSP: How can CDMOs and customers work to better anticipate the future?​

TB: Customers should be aware of the strengths and weaknesses of their newly developed APIs from the beginning, especially to address the latter as early as possible. This will not only improve the probability of success of an API candidate but can ultimately even enhance the API´s properties and thus patient benefit.

An ideal CDMO should elaborate on potential weaknesses early on and consult their customers on potential measures to avoid respective risks during development and manufacturing. One very important but often neglected element is formulation development.

Each drug product has a formulation, of course, but what makes the difference is to not just go with a simple buffer, but to develop an advanced formulation tailored to the specific needs of the API. Taking advantage of the right and especially high-quality excipients is key and contribute to many factors such as stability, purity, and safety of the final drug product.

OSP: Similarly, where is the future of excipients headed—what trends are you seeing and how might they impact what’s down the road?​

TB: Excipients can exhibit various functions within a pharmaceutical formulation and are of high importance to adjust and improve the final drug’s characteristics. With recent trends towards more complex and demanding APIs, the role of excipients will certainly increase and significantly impact the probability of successfully bringing a drug to the market. The requirements for excipients themselves will certainly increase as well, as regulatory requirements are becoming more and more demanding.

A trend toward more controlled and documented production processes, as well as additional parameters like endotoxin and bioburden testing, is becoming more common. Another trend we expect to see in the future is additional quality attributes relevant for specific applications, such as minimizing impurities that impact API stability. With many of our products, we are even ahead of the constantly increasing regulatory and quality requirements.

OSP: Can you please talk about the innovations and trends speeding up API manufacturing? How can we achieve a balance between speeding up API manufacturing and satisfying the needs of CDMOs and customers, without sacrificing quality?​

TB: Raw material handling is a critical factor in influencing manufacturing speed. CDMOs typically require the handling of multi-ton quantities of raw materials in a short time to assure quick change over between batches. Many excipients used for buffer preparation however tend to stick, cake, or even solidify over time. Handling such chemicals can cause severe delays when it comes to emptying the primary packaging, weighing, and processing the material.

At MilliporeSigma, we offer a portfolio of granulated excipients that are specifically developed and optimized to reduce caking, improve handling, and speed up manufacturing processes.

OSP: What about regulatory challenges — how can manufacturers meet these marks, manage risk, and develop new/novel ingredients?​

TB: Ensuring the compliance of pharma and biopharma products involves the compilation of a vast amount of data, which can be time- and resource intensive. In order to facilitate and accelerate this process, we developed our Emprove Program. It includes hundreds of pharma raw and starting materials and a selection of filtration and single-use products. Each product in the portfolio is complemented with three different types of dossiers supporting our customers throughout the different stages of operations: qualification, risk assessment, and process optimization – all designed to help our customers speed up their way through the regulatory maze.

OSP: How can companies like yours contribute to innovation in products and practices in this area?​

TB: Given the critical role that excipients play in bringing new treatments to market, it’s imperative that we continue to innovate in this area. One way to do this is through active research in developing fit-for-purpose excipients, including novel excipients.

Novel excipients can provide many benefits and elevate the API´s characteristics, e.g. stabilizing even the most demanding APIs and enabling concentrations which were not achievable before.