(MINI WEBINAR) Elevating your approach to high potency APIs

In this mini webinar, Senior Technical Manager at our Germantown site, Matt Miklas, will be discussing the growing demand for high potency APIs, some of the keys to HPAPI success, and the capabilities we have to offer here at Sterling.

In recent years, high potency APIs have seen a rapid uptick in growth. In fact, it’s estimated that more than 25% of drugs on the market today are highly potent. HPAPIs are appealing because of their ability to enhance therapeutic efficacy by delivering highly targeted treatments.

As you see here, the global HPAPI market is expected to reach a value of $40 billion in the next several years, and the contract manufacturing market for HPAPIs is expected to grow by 9.0% through 2030—more than doubling its value from 2022. This represents one of the fastest growing areas in the pharmaceutical industry, and it’s clear that HPAPIs are here to stay.

So, what specifically is driving the growth in HPAPIs and the rising demand for outsourced services in this area?

As I mentioned, high potency APIs have the ability to provide highly targeted treatments using lower doses than other therapeutics can. As a result, HPAPIs have shown promise in treating serious and chronic conditions like asthma, diabetes, cardiovascular diseases and more. But there’s one area in particular I’d like to call out—oncology.

Cancer treatments have been one of the most significant drivers of HPAPI growth,

. In addition, highly potent payloads are utilised in antibody-drug conjugates, another growing area for targeted cancer treatment. 60% of oncology drugs in development today involve highly potent intermediates, and given that nearly 1 in 3 new drug approvals over the past several years have been for cancer, it is clear why HPAPIs have become a key focus. Today, over 90 small molecule targeted cancer treatments are on the market, with many more in the pipeline.

Another key area I’d like to call out is the evaluation and classification of HPAPIs. API potency is based on occupational exposure level, or OEL. Then, the level of containment is determined using occupational exposure bands, with levels 4 and 5 requiring the highest levels of containment. Any API with an 8-hour average OEL under 10 µg/m3 is generally considered to be potent.

But organisations should not consider OEL alone when determining containment strategy. It is also important to factor in active ingredient percentage, physical composure of the API, like whether it’s a powder, steps of the process, and the level of employee exposure when working with the material. With all of these factors at play, organisations often tend to err on the side of caution when shaping a containment strategy.

In addition, advances in toxicological assessments such as high-throughput screening and computational biology have enabled more efficient and effective classification. As assessments have improved, more and more APIs are considered highly potent.

Outsourced HPAPI services are also on the rise because of challenges implementing these capabilities internally. Because HPAPI development and manufacturing requires multiple levels of containment, specialised expertise and extensive training on proper handling and containment measures, the cost and time commitment involved in bringing these capabilities in-house is quite high. In turn, many organisations turn to contract manufacturers, with 50% of industry professionals expressing plans to outsource HPAPI services in the near future.

Outsourcing HPAPI development and manufacturing has become even more prevalent since the onset of the COVID-19 pandemic, given the pressure to produce affordable drugs quickly amid supply chain delays early on.

Another reason for the growth of HPAPIs, and of HPAPI outsourcing, is the rise we’re seeing in ultra-potent APIs. Some therapeutics, including ADC toxin linkers and certain psychedelics used, can have extremely high levels of potency, requiring especially high levels of containment and, in the case of psychedelics, often the infrastructure, systems, and licensing necessary to handle controlled substances.

Containment for these ultra-potent APIs can go down to the single-digit nanogram levels, much lower than those of typical mid-range HPAPIs. Outsourcing is even more prevalent for these materials, as even organisations that are equipped to handle typical HPAPIs may not have the high levels of containment required to support these compounds.

Now, given these realities, what is really needed to maximise success in HPAPI development and manufacturing?

The first is purpose-built facilities. As I discussed, HPAPIs have a range of highly specialised requirements. With the spike in demand for HPAPIs, we’re also seeing instances of retrofitting non-specialised facilities to be suitable for high potency. However, this can present hazards and a range of other challenges.

It’s really critical to have specialised facilities and equipment specifically designed for high potency projects—with controls like multiple layers of containment, asset flexibility to handle a range of process requirements, and a facility-wide awareness of safety measures. For example, if controls within glove box isolators themselves fail, it’s important to have these isolators contained in downflow booths to prevent highly potent materials from entering the GMP suite that houses them. On top of that, airlocks within the containment suites themselves should be in place to prevent potent materials from making their way into the wider facility. A multi-layered approach ensures that HPAPI operations are as safe and controlled as possible.

In addition, it’s important that a facility has the ability to support a range of potencies and levels of containment. For example, additional studies may be run on potent material that determine it is less potent than originally anticipated, requiring lower levels of containment. On the other hand, material may turn out to be more potent than expected, necessitating additional containment. The ability to support the full range of potency and containment in the event that any new information alters the containment strategy is crucial.

Even with the appropriate controls in place within the facility, it is important to note that there is no one-size-fits-all approach to containment. The containment strategy should be tailored based on the project’s specific requirements. Failing to use sufficient levels of containment creates significant risk for the team members working with highly potent materials, as well as the facility at large. On the other hand, using high levels of containment when it is not necessary based on the material’s potency can create added costs and project delays.

On top of tailoring the containment approach based on a given project, asset flexibility is also key to supporting a variety of process considerations. HPAPI projects can come with a range of other requirements, like cryogenics, milling, high pressure, chromatography, lyophilization, and much more. A facility should have the ability to handle HPAPIs safely in conjunction with these other key requirements, as well as to continually support a project as it scales.

Ongoing testing and monitoring are also critical for HPAPI success to ensure that target containment levels can be achieved and maintained throughout the process. Containment verification testing of the suite should be carried out before any HPAPI work begins, using a safe substance. The goal of these studies is to affirm that the suite can properly contain the high potency API, and that the operators are properly trained for safety.

Product-specific performance qualification and hygiene monitoring should then continue as the project progresses, including surface and air monitoring. This helps to ensure that the equipment and processes perform as anticipated over the course of the entire project, and that any changes can be addressed proactively.

Finally, we’ve touched on this a bit already, but specialised teams and processes are really integral to the success of any HPAPI project. Equipment is only as effective as the people operating it. Team members working with HPAPIs should have extensive training in containment, controls and cleaning. They should also know how to respond in the event of any issue or emergency that may arise.

Team members must also wear the proper PPE at all times, and the facility should have measures in place like designated gowning and de-gowning areas and misting showers to prevent operators working with high potency intermediates from bringing any lingering material into the larger facility.

Training is important not only for those directly handling HPAPIs, but also for team members throughout the entire facility. In the event of an emergency, everyone must know how to properly respond to keep everyone safe.

Now that we’ve covered some of the key things necessary to set an HPAPI programme up for success, I’d like to go over some of what we have to offer here at Sterling. You’ll see a number of our differentiators here.

We combine more than 50 years of expertise in complex and hazardous chemistry with over 15 years of experience in HPAPIs. We have the ability to support projects from discovery through to commercialisation here at Sterling, which means that we can support HPAPIs in conjunction with a variety of other process considerations and across the entire lifecycle. Our isolated cGMP containment suites can support batch sizes up to 10 kilograms, and our containment verification always includes multiple iterations to support ongoing safety.

Another thing I’d like to call out is our ability to offer toxin-linker synthesis for antibody-drug conjugates. This is done in collaboration with our Deeside, Wales site, which specialises in ADC discovery, development and manufacturing.

Finally, we ensure that all of our team members, whether working directly with HPAPIs or in proximity, receive the proper training to handle these materials safely and effectively respond in case of an emergency. The safety of our team is of the utmost importance when working with highly potent materials.

All of this is backed by our commitment to true scientific partnership, as we collaborate closely and regularly with our customers to address their project requirements, tailor our approach, and ensure their ongoing success.

If you’d like to learn more about our HPAPI services, I invite you to visit the Knowledge Hub on our website, sterlingpharmasolutions.com, for other insightful resources. You can also contact one of our expert team members here.