Risk Analysis and Containment Solutions for High Potent APIs (HPAPIs) Manufacturing

The development of technical solutions for this new approach to containment must necessarily start from embracing the same approach to the topic used by the pharmaceutical companies, and adopt the very same risk analysis principles used in the industry to ascertain the hazards for each and every product, from OEB 1 to OEB 5-6 degree toxicity.

Once the risk analysis has taken into consideration the widest possible range of scenarios, the equipment manufacturer is in a position to develop new technological solutions to effectively satisfy the full range of containment needs, from low through moderate to high.

Case study

Taking into consideration the entire process from loading to unloading, in particular for the tableting and capsule-filling manufacturing phases, IMA ran a comprehensive FMECA Analysis (Failure Mode, Effects and Criticality Analysis) to establish a complete picture of potential risks in countless environments, process types and software failure situations.

This represents the standard method recommended by ICHQ9 “Quality Risk Management” as well as being in line with GAMP5 – A Risk Based Approach to Compliant GxP Computerized System.

Each single function and sub-function in the process was assessed for risks, carefully identifying potential failures and potential effects.

Once identified, each potential failure was evaluated according to the following criteria: severity, occurrence and detectability.

At each of these three criteria, a value of high, medium or low has been assigned. Direct correlation between risk severity values and risk occurrence values enables to obtain the Risk Class of each potential failure, which can be high, medium and low.

Once the risk class has been established, the third criteria, detectability, is introduced and is placed in relation to risk class to produce what is called risk priority.

This too can be classified as high, medium or low. Consequently according to the risk priority for each potential failure, we are able to establish the corresponding corrective action needed to reduce the risk to an acceptable degree.

Targeted containment strategies

The containmentnstrategy has been based on the risk analysis referring to the entire process.
This includes, For solid forms, product transfer at machine inlet and outlet, tableting and filling stages, as well as end-of-batch management and cleaning procedures, undoubtedly a critical phase.

Below a 3tier proposal by IMA:

  • The first category of containment systems is called Dust Tight. It ensures effective containment up to and including OEB 3 level toxic API’s during normal production conditions.
  • Dry Containment solutions are suitable for OEB 4 level and
  • THC (Total High Containment) category equipment will handle OEB 5 toxic products throughout the process.

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Resource Person: BARBARA PIROLA

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