The development and manufacture of drug products containing highly potent active pharmaceutical ingredients (HPAPIs) is in demand. Recent data suggest that between 2023 and 2030, the small molecule drug discovery market will register a compound annual growth rate (CAGR) of around 8%. This is particularly relevant in the field of oncology, which accounts for around 35% percent of small molecule drug candidates, around half of which contain HPAPIs.
The High Potent Market and the Role of a Specialist CDMO by Dr. Rebecca Coutts | As seen in The PharmaNetwork | October 2023.
The Highly Potent Market
The development of targeted therapies and precision medicines has revolutionized cancer treatment, resulting in more effective and potentially less toxic therapeutic options for patients. Furthermore, regulatory agencies including the FDA have implemented accelerated approval pathways, fostering innovation and promoting faster commercialization of novel oncology drugs. In this dynamic landscape, the role of formulation development becomes even more critical, as it ensures the successful translation of these breakthrough discoveries into safe, effective, and accessible drug products for patients, whilst ensuring a greater speed to market for sponsor organizations.
In recent years, drug development organizations have increasingly turned to outsourcing as a way to optimize resources, leverage expertise, de-risk investment, and accelerate drug development timelines. This trend has been particularly prominent in the field of oncology, where the need for novel therapies and personalized medicine has led to a surge in research and development activities meaning the importance of partnering with the right contract development and manufacturing organization (CDMO) can hardly be understated.
Safe handling of highly potent molecules is complex, and the associated regulatory requirements are growing. As a result, pharmaceutical companies recognize the importance of selecting the right partner for the development, manufacturing, packaging, and commercialization of products containing HPAPIs. Some companies work with one CDMO throughout the entire lifecycle, while others partner with multiple vendors. To ensure success, teams must conduct due diligence to identify CDMOs that meet their safety, regulatory, technology, process, expertise, economic, and schedule requirements.
Essential Attributes for success from development to launch
- Formulation Development
Successful formulation development requires the engagement of highly experienced teams across a variety of disciplines, such as analytical, manufacturing, quality assurance and control and, of course, formulation and process development. These cross-functional teams should possess a comprehensive knowledge and understanding of their equipment and processes, and a strong awareness of alternative development and manufacturing methods. This enables them to determine how various formulation attributes can impact the final drug product, both positively and negatively, and advise their sponsors accordingly throughout the process.
In terms of technology and manufacturing equipment, it is beneficial to work with a CDMO with facilities designed for small-scale operations while also offering in-house scalability for large-scale clinical and commercial manufacturing. This flexibility enables a CDMO to accommodate a wide array of product requirements and adapt to different formulation and process challenges. Access to an extensive range of equipment and processes ensures that challenges can be addressed, and the most suitable solution for each unique project can be found.
- Scalability for lifecycle management
Often, companies outsource the early-stage development and clinical manufacture of their highly potent oncology drug product due to many “unknowns.” The intent may be that once formulations and manufacturing processes have been established and optimized, they will transfer activities back in-house. However, owing to the many processing complexities and, perhaps, required internal capital investment of this strategy, it is often deemed beneficial to continue the outsourcing relationship. Comparing a CDMO’s ability to support product needs from development through to commercialization will be imperative and could prevent the need to change vendors — thereby reducing risk, time and the associated costs of the development programme. In addition, HPAPI-related outsourcing decisions should not be limited to the initial commercial launch of a product; it can take many years beyond commercial approval for an oncology therapy to reach peak demand. The approved process validation scale may not meet peak demand, meaning that a secondary supplier may be required. The sponsor company should futureproof their decision and assess the maximum commercial manufacturing and packaging outputs an outsourcing partner may offer and their ability to scale-up and meet such anticipated peak demands.
- Containment strategies and risk assessment
Vendor assessment should be based on the CDMO’s ability to handle and process HPAPIs in a way that keeps operators and the environment safe and complies with regulatory requirements. Organizations may use different terms when classifying HPAPIs: occupational exposure bands, occupational health categorizations, control bands and some larger companies may use their own in-house classifications. Irrespective of the terminology used by the sponsor company, the chosen partner should have an established and robust risk assessment framework to make an accurate assessment of the safety and health parameters of the compound.
Occupational exposure limit (OEL) is universal terminology understood by all. Companies need documented OELs as well as industrial hygiene experts who can interpret OEL data and evaluate the workplace requirements. The importance of making an accurate OEL assessment should not be underestimated as, when it comes to highly potent compound safety, facilities must develop containment strategies that strike the right balance to ensure the appropriate solution for the product. A risk assessment framework is required in order to determine the probability of exposure based on a combination of occupational hygiene and containment procedures in place remembering that a risk assessment is not a one-off exercise, but something that needs to be monitored and repeated as additional data becomes available. Therefore, selecting an outsourcing partner based on their risk assessment framework and approach to contained engineering solutions should form part of the primary selection criteria.
So how should you select a potential outsourcing partner?
The importance of selecting the right partner for managing the development to commercialization lifecycle of products containing HPAPIs is critical. As well as ensuring the safe handling of products, identifying and assessing a partner with the specialist capabilities to take a product through to commercial launch with a successful regulatory history is of equal importance. Some companies may work with multiple vendors during the clinical development to commercial cycle, whereas others choose to identify and work with one partner able to manage all the different stages of the process. Whichever path is taken, conducting full due diligence as part of the vendor selection process to ensure that a partner is able to meet all required criteria will be key to a successful project.
- Working with one or multiple vendors
It would appear that working with one specialist CDMO from early-stage drug development through to commercial launch is the ideal scenario. This approach reduces the number of handoffs, technical transfers, and, perhaps, risk to the project. Through this approach, all data and experience of the product remain in one place, reducing the likelihood of gaps in scientific knowledge and product expertise.
Although working with one partner might be the ideal scenario, it is worth mentioning that decisions are often based on time and money, perhaps driven by the phase that the product is in within the lifecycle. It should also be noted that not every CDMO is able to handle the full lifecycle, some CDMOs may be more suited to smaller-scale early development whereas others may have capabilities more suited to large-scale commercial manufacturing. It may, therefore, be prudent to assess a potential CDMO partner based on their full service offering even if the planned strategy is to use multiple vendors.
Investing in this approach provides the flexibility to remain with one partner should intentions change as the project evolves. Regardless of how many CDMO partners a company may or may not use, the sponsor pharmaceutical company itself should always maintain full knowledge and ownership of the project and data. This is crucial both as the proprietary owner of the product, but also in the event of needing to transfer knowledge to an alternative CDMO vendor.
- The potential benefit of streamlining supply chains
With valuable life-saving oncology drug products, streamlining the product supply chain may be beneficial. Reviewing a vendor’s full-service offering, whether it be provision of in-house analytical support, dedicated highly potent packaging solutions or global distribution to support clinical trials and/or product launch, will prove beneficial if the scope of outsourcing requirements were to change. Leveraging end-to-end expert solutions may minimize overall supply chain complexity and risk.
PCI Pharma Services (PCI) response to market need and partnership with clients
PCI Pharma Services (PCI) is a global, integrated CDMO providing end-to-end development to commercialization services to the pharmaceutical industry including, development and manufacturing, clinical trial services, commercial packaging and launch services. With over 35 years of experience in the processing of highly potent drug products, PCI has built on this heritage to become an industry-leader, providing state-of-the-art processing of products containing highly potent actives on behalf of a global customer base.
Harnessing significant experience gained over many years prior, in 2013 PCI opened its first multi-product contained manufacturing facility (CMF) for the development and manufacturing of highly potent drug products. Using a clear design for manufacture philosophy and the very latest in fully contained engineered technology, the small to largescale equipment trains deliver geometric scale-up as products progress, guaranteeing reproducibility from development to commercial scale to support customers throughout the product lifecycle.
Since the launch of this new facility, the demand for the processing of highly potent drug products has continued, largely driven by ongoing research in the oncology market as well as the successful progression of products during this time through to later stage clinical phases and subsequent commercial launch. In response, PCI further invested in a second large-scale contained manufacturing facility delivering increased capacity for commercial-scale high potent manufacturing. At the same time, additional investment was made in a co-located, specialist high potent packaging facility (HPPF) able to deliver small-scale clinical to commercial-scale packaging of drug products manufactured within the contained manufacturing facilities. With both becoming operational in the summer of 2022, PCI ensured that customer demand for specialist expertise would be secured long-term.
PCI’s development, manufacturing and packaging capabilities are further complemented with full in-house analytical services also located at the same site, becoming a true single vendor solution for our global customers. The investments made over the last decade or so were based on market and customer demand for the outsourcing of services to a truly specialist CDMO and the requirement to reduce both supply chain complexity and overall risk. Being a “specialist one stop shop” for the processing of highly potent drug products protects the knowledge and experience gained throughout the lifecycle of the project, meaning that PCI is not just an extension of the sponsor companies with which we work, but a fully immersed and invested partner in the aim of delivering life-changing therapies to patients.
- What makes PCI different?
The entire premise of PCI’s contained manufacturing and packaging facilities was based on the objective to utilize the very latest in containment technology, removing the need for traditional personal protective equipment (PPE) to ensure the highest levels of safety for both operators and the environment. This combined with the design for manufacture, delivers a true end-to-end solution from development to launch.
Building on 35 years in potent processing and with an unrivalled regulatory track record, PCI offers two purpose-built manufacturing facilities in addition to a stateof-the-art packaging suite all utilizing the very latest in containment technology, enabling the safe development, clinical, and commercial scale manufacture of products with an Occupational Exposure Limit (OEL) as low as 0.01µg/m3. The facilities include multiple levels of containment built into the design. Dispensing of API is undertaken within isolators and subsequent processes within appropriately contained equipment ensure operator safety and preventing cross-contamination. Our fully integrated facilities utilize common equipment trains from development to commercial scale, with geometric scale-up delivering reproducibility and ultimately speed-to-market.
Through these facilities, PCI offers high potent drug product manufacturing and packaging at all stages of the product lifecycle for a variety of dosage forms including, tablets, capsules, powders, gels, creams oral liquids, solutions, suspensions, emulsions, suppositories, pessaries, granules for reconstitution and drug in capsule/vials via micro dosing technology.
The growth in oncology research is predicted to continue and with a high proportion of therapies being small molecules containing highly potent actives, the trend in outsourcing to a specialist CDMO partner for drug product manufacture becomes even more critical.
Advances in the molecular understanding of cancer with the increased focus on developing targeted therapies, coupled to regulatory support to get novel treatments to market quickly, has changed the outsourcing paradigm for highly potent oncology drug products. Biopharmaceutical companies recognize the importance of selecting the right partner for the development, manufacture, packaging and commercialization of their oncology products containing highly potent active pharmaceutical ingredients. With the growing complexities of the safe handling of such molecules and the associated regulatory focus, companies looking to outsource must conduct due diligence to identify truly specialist CDMOs that offer the following: safe, regulatory compliant, scalable and flexible processes; additional in-house services; and end- to-end solutions that can be tailored to meet changing needs throughout the development lifecycle to global commercial supply.