Meeting the Challenges of High-Potency API (HPAPI) Production

The global High Potency Active Pharmaceutical Ingredients (HPAPI) market is estimated to grow to USD 41,831.63 million by 2028 at a CAGR of 9.27% according to a report published by Mordor intelligence. The growing burden of cancer across the world is expected to increase demand for HPAPIs that will be helpful in the production of effective medications. HPAPIs are primarily used in production of formulations for high potent drugs. It is because of their capability to target precise disease cells including cancer cells. However, the primary challenge for CDMOs and biotech organizations is to classify any given API along with all necessary data requirements for Occupational Exposure Limit (OEL), Occupational Exposure Band (OEB) potency, and finally toxicity.

“The lower the OEL limit, the higher the potency, which demands rigorous containment and controls. For the NCEs with no established OEL, the risk assessment process and strategy should be worked out by reviewing preclinical study results, third-party assessment by toxicology and environment, health and safety (EHS), literature searches, and AMES/genotoxic assessments. Biotechs working with early-stage NCEs must adopt a conservative approach to prioritise safety for their HPAPIs in discussions with contract development and manufacturing organisations (CDMOs) and other scientific partners”, mentioned Dr. Kishore Hotha, Global Head of Analytical Research & Development, Veranova.

HPAPI manufacturing and development are surrounded by some industry challenges. Apart from proper classification of APIs, these are the aspects that make organizations think over the problems that may arise from negligence of these.  

Containment Challenges

The latest mandates on HPAPI manufacturing and development has increased the emphasis on the containment challenges. The guidelines are utterly essential in ensuring regulatory compliances, environmental and personal safety within the manufacturing premises. The Occupational Exposure Limits (OEL) for HPAPIs being extremely low which implies to the fact that even the exposure to the slightest of volumes can result in severe health hazards for the workers. The risks associated with cross contamination of products inside a factory cannot be overlooked as well.

Isolated manufacturing zones that are specially designed for the production of high-potency products is primary requirement for handling of HPAPIs. In these specifically designated zones, the contamination of hazardous particles must be prevented and design must be meticulously engineered. In this regard factors like robust deign facility, rigorous controls and specialized equipment is necessary to maintain proper engineering for containment zones. The usage of HEPA filters, dedicated air handling units, closed manufacturing systems and most importantly stringent decontamination protocols are also imperative in this aspect. HPAPI manufacturing organizations must delineate all clearly refines zones, restrict human movements and deploy modern containment technologies in order to ensure safe handling of high potency compounds.

In this regard, ILC Dover supplies and manufactures a range of HPAPI containment solutions, including drum transfer systems and automated air controls. These provide an added layer of safety when dealing with highly potent or dangerous materials.

Scalability Challenges

Early discovery of molecules require interventions so that they can be transformed into commercially feasible products. In this case, scalability becomes a challenge. Organizations needs to either have advanced infrastructure and equipment to scale the molecules up or require excellent connections for outsourcing.  Compared to traditional APIs, HPAPIs have different batch volumes and scales which is why in order to meet the demand in the market, HPAPIs require production in lesser volumes for the minimization of financial risks.

To give an example, BASF provides custom synthesis and manufacturing services for pharmaceutical compounds, including HPAPIs and have experience in developing more scalable processes for HPAPI production.

Challenges related to Outsourcing

For an organization to have an in-house HPAPI manufacturing unit, various aspects must be taken care of. The facility must have the specialized engineering and equipment along with the commitment to abide by the dynamically changing guidelines of the industry and maintaining all regulatory standards. In this case, outsourcing the manufacturing from Contract Manufacturing Organizations (CMOs) and Contract Development and Manufacturing Organizations (CDMOs) of the HPAPIs can be of great help in reducing the infrastructure related constraints for an organization and free it from all kinds of burdens related to manufacturing. Two instances can be mentioned in this regard. First is, an organization can facilitate the conduction of R&D in-house and get the manufacturing done by a CMO and on the other hand, a CDMO can initiate the research for a company and enable them to start off with an in-house manufacturing unit.

AMRI (Albany Molecular Research Inc.) is a global contract research and manufacturing organization (CRMO) that provides services in drug discovery, development, and manufacturing and have expertise in handling high potency compounds, including HPAPIs.

“Safety and quality protocols from the handling perspective, expert review from toxicologists and EHS teams, and developing a containment strategy with a measure of exposure are the key factors that need to be worked on between CDMOs and customers. Robust, sensitive analytical methods are critical for CDMOs for the detection and cleaning strategy”, said Dr. Hotha.

The most anticipated ascend in the HPAPI market has presented enormous opportunities for the pharmaceutical industry. This growth is laying solid foundations influenced by escalating demand for targeted therapies and personalised medications. HPAPIs are playing a vital role owing to their potency in therapeutic efficacy. This is one of the biggest commercial opportunities that is being driven by the potential to command premium pricing owing to the specialised nature of HPAPIs. Furthermore, the growing problemsin chronic diseases is further catalysing the demand and creating an enhanced revenue stream for all HPAPI manufacturers.