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PharmTech.com Trends in Formulation eBook September 2024 Pharmaceutical Technology ® 37 Industry trends in order to ensure that adherence to the treatment is being managed appropriately." Gary Watts, senior manager in Analytics at Abzena rec- ommends early discussions regarding the target product profile and the end user to ensure appropriate strategies are used. "Obvious strategies include avoiding the use of sugar-type excipients if the end-user group are those prone to conditions such as diabetes," says Watts, "and avoiding the use of sodium chloride for those with on low-salt diets for hypernatremia or hypertension, for example." Quality formulations Novel excipients and new delivery systems present chal- lenges for quality control and compliance with regulations and require a thorough understanding of modes of action and degradation pathways, according to Levet. "It is also essential to conduct thorough development programs cov- ering stability, compatibility, systematic risk assessments, as well as to establish robust analytical methods to assess the quality of these innovative formulations," says Levet. Ensuring quality is just as much a part of formulation as it is in manufacturing when it comes to medicines. Testing and validation processes to ensure stability, efficacy, and safety of new formulations must be rigorous, according to Biswas. "As an example, mRNA and lipid nanoparticle (LNP) technologies are becoming increasingly import- ant in vaccine development. These advancements have extended beyond infectious diseases and into oncology, where mRNA formulations are being explored for cancer research. Formulating mRNA into LNPs involves creating new lipid libraries and establishing precise quality profiles and analytical tools," says Biswas. "Advanced formula- tions like these necessitate robust analytical methods to monitor and control quality throughout the development and manufacturing processes. As such, the pharmaceu- tical industry must continuously evolve its quality assur- ance and control measures to address the specific require- ments and challenges posed by innovative formulation technologies." Phil Challis, SVP Manufacturing at etherna, agrees. "In the RNA-LNP field, we mainly see a concern regard- ing the translatability of process changes or deviations toward clinical impact. Not all players in the field master all methods or have the know-how and knowledge to be able to make this call." "The pharmaceutical industry is highly regulated and patient safety is at the forefront of regulation," says David Ferrizzi, director of New Product Development, at Col- orcon. "Every region is unique, but there are a few chal- lenges that are universal in the industry. One example is the industry's focus on controlling the nitrite level in pharmaceuticals. Excipient providers … must understand the role we play and how the excipient impacts the API. Additionally, the industry continues to focus on impuri- ties and how to handle them within the drug formulation, and topics like reducing TiO 2 ." Patil stresses that combination products have specific human factors that should be considered with ensuring quality, as opposed to traditional products. "In those cases, the user tasks, potential errors and harms, and overall risk must be assessed and addressed as part of the devel- opment," says Patil. "In addition, there would also need to be validation activities performed for any computer hardware and software introduced as part of the dosage process." Hanns-Christian Mahler, CEO and board member of ten23 health, stresses that quality should be a priority. "A formulation that cannot be reliability and reproducibly manufactured with adequate quality is not going to be a product," says Mahler. "There are various examples of where formulation technologies enabled specific chal- lenges to be addressed and provided improvements, yet their manufacturing was not acceptable, either from a quality or from a cost standpoint. For the whole range of sterile products, one example is the need to ensure an 'aseptic process' and guarantee sufficient sterility assur- ance, which again is essential for patient safety." Future of formulation Sustainability appears to be gaining greater focus in the industry, and Patil points to this as interesting in how it may impact formulation. "It's already being implemented in drug substance manufacturing by reduction of solvents or substitution of more environmentally friendly mate- rials," says Patil. "I think a natural extension of that will eventually apply to drug product manufacturing. It's rea- sonable to expect that we'll be asked to select biodegrad- able and sustainably sourced excipients, when possible, in order to minimize the environmental impact." Mahler says to look at subcutaneous administration and drug/device combination products as two trends to look for in sterile dosage form formulation. He further adds that, "in the field of CGT [cell and gene therapies], specifically viral vector and cell therapy, I think there must be more focus on the actual product formulation and aiming to develop refrigerated (2–8 °C) products, moving away from frozen products using 'traditional' off-the-shelf formulations." Gadgil sees biologics creating promising formulation trends that will have a significant impact. "One major area of interest is the development of biologic formulations that are stable at ambient temperatures. This advance- ment would simplify distribution logistics, reduce costs, and improve access to therapies, particularly in regions with limited cold storage infrastructure," says Gadgil. "Another exciting trend is the pursuit of non-invasive de- livery methods for biologic molecules. Innovations in oral, nasal, pulmonary, or transdermal delivery systems offer the potential for more convenient and patient-friendly therapies. Successful development in these areas could greatly enhance patient compliance and reshape the way biologics are administered." ■