Current Edition

High Potent Manufacture

The global market for drug products containing highly potent active pharmaceutical ingredients (HPAPIs) is currently on a growth fast track. Data indicates a Compound Annual Growth Rate (CAGR) of 8.7% to 2032, with oncology a major driver, capturing a market share of 76% in 2022.1 Additionally, even though biologic dosage forms are experiencing significant growth, the shift from intravenous (IV) dosing towards solid oral dosing is likely to gain momentum; the main driver for this is patient experience, as taking solid oral dosage forms is far less stressful than spending days or weeks in hospital receiving chemotherapy infusions.

Therefore, the role of CDMOs that are able to develop, manufacture and package drug products containing HPAPIs is more vital than ever. There should be a robust approach to all stages of the process, including containment strategies, formulation development, scalable manufacture and potent packaging operations.

Containment Strategies

Throughout the pharmaceutical industry, there is a lack of consistency regarding the assignment of Occupational Exposure Limits (OELs) to specific bands. It is therefore critical to have a unified understanding of all relevant definitions, as described below.

• PDE (Permitted Daily Exposure), also known as ADE (Acceptable Daily Exposure), represents a substancespecific dose that is unlikely to cause an adverse effect if an individual is exposed at or below this dose every day for a lifetime.

NOEL (No Observed Effect Level) is the highest tested dose at which no “critical” effect is observed. If the critical effect is observed in several animal studies, the associated NOEL should be used to calculate the PDE value.

OEL (Occupational Exposure Limit) is the average concentration load of an airborne active pharmaceutical ingredient (API) in ?g/m3 that’s acceptable during an 8-hour timeweighted average with no negative impact on workers/environment.

• OEB (Occupational Exposure Band) is the banding of OEL into ranges for which appropriate measures to protect workers and facilities/equipment can be defined in common for APIs with different OELs within this band.

• COSHH (Control of Substances Hazardous to Health) assessment.

Table 1 below illustrates the difference in banding applied by two pharmaceutical companies, demonstrating that there is a significant lack of common terminology, and therefore true understanding, of potent classification.

When developing and manufacturing highly potent drug products, there should always be an OEL monitoring program at each stage of the process. Strict cross-contamination controls are essential, with a risk assessment performed in accordance with four principle modes:

• Airborne;

• Mechanical;

• Personnel transfer;

• Retention of product on contact surfaces.