HPAPIs - Smart monitoring and verification for containment strategies
Michael Avraam, global product manager at ChargePoint Technology discusses the evolution of containment strategies, specifically within the role of containment verification and monitoring technology.
Fuelled by growth in the biopharma sector and the oncological and immune-suppressant fields, the pharmaceutical manufacturing industry is seeing a surge in demand for high potency active pharmaceutical ingredients (HPAPIs). This is leading many manufacturers to consider increasingly innovative containment strategies to meet these high potency handling requirements.
Industry landscape
The biopharma market is growing significantly, not least due to an increase in the oncology sector, and the containment solution market is expected to grow rapidly in line with this over the coming years. There is a notable increase in conventional drug manufacturing using HPAPIs; a market that is expected to be worth $25.11bn by 2023, up from $2.64 bn in 2014.
The requirements in high potency manufacturing environments are complicated as every containment solution needs to overcome issues relating to productivity and operability. Market diversification has opened the door for more technological innovations to safeguard drug products as well as the operator within this process.
Considerations within containment testing
Effective verification of containment performance is becoming increasingly important thanks to the proliferation of innovative technologies such as SBVs and investment surge in high potency facilities and equipment to manage the risks associated with HPAPI handling. As a result, this is driving innovation in containment strategies.
The SMEPAC (Standardised Measurement of Equipment Particulate Airborne Concentration) assessment outlined by the International Society for Pharmaceutical Engineering (ISPE) primarily focuses on how a containment device will perform within laboratory conditions, not in the real-world manufacturing environment the device is destined to be used in. Experts now feel that the random nature of this process is hindering progress to achieve a specific measure of containment for equipment or devices.
Verification within SMEPAC: laboratory versus reality
The SMEPAC guidelines permit a certain amount of flexibility in testing protocols and analysis of data so it is therefore critical to understand these variations and the challenges posed by potential differences in the interpretation of results.
The SMEPAC guide suggests a range of surrogates with varying particle sizes and levels of detection when using placebos during validation testing, including lactose, paracetamol, mannitol and naproxen. However, it’s important for those running the tests to ensure the placebo used is not only reflective of the real-life API eventually to be used but also to ensure that each supplier has tested the solution with the same or similar placebo to ensure best comparable results.
Deviations in sampling and monitoring equipment can also lead to variations in results, even if the test has been carried out with the same equipment and a common placebo, under identical test conditions.
It’s true that the testing protocols detailed by SMEPAC allow for inconsistency, for example in transfer quantity but the very nature of providing a ‘suggested’ weight range means that variations in volume will likely result in inconsistent results when testing a device within the laboratory to that of its final manufacturing environment.
Results from laboratory validation tests are ultimately used to qualify the selection of the required containment technology for a manufacturer’s process. However, there is a disconnect between the laboratory and manufacturing setting and test data could prove to misrepresent reality. Consequently, it is risky to presume that performance will be the same, and it’s important to consider the variables when interpreting data and to use this information as a guideline only.
As human intervention is present throughout pharmaceutical manufacturing processes, solutions must be considered to manage potential operator or airborne contamination risks and validation testing needs to reflect this operator intervention while not hindering productivity and operability.
The containment solution should also be validated at each step where potential exposure is present in a real-world environment. This would need to include a full risk assessment for the entire process.
Real-world monitoring for improved containment risk control
In a manufacturing environment, frequent monitoring and preventative maintenance helps to safeguard the reliability of the containment solution and there are several approaches available to manufacturers for the monitoring of containment system performance.
More traditional approaches have predominantly involved manual checking; however wireless monitoring is an economic approach that provides continuous reporting and data monitoring, allowing users to assess containment technologies simply and safely in hazardous environments. This feedback allows for proactive management of equipment maintenance which prevents failure and reduces downtime.
With a full audit trail, maintenance, health and safety and compliance teams can use this information to proactively manage their respective programmes. This also minimises the likelihood of staff exposure to potentially hazardous materials like HPAPIs by highlighting potential containment issues before they arise.
Final thought
Drug manufacturers will continue to deploy increasingly innovative containment strategies to meet the growing demand for high potency handling, creating a need for new approaches to verification and performance monitoring. While widely adopted and welcomed, it’s important for manufacturers to understand the clear differences between laboratory and manufacturing environments and the limitations of the SMEPAC guidelines. Whilst at present traditional containment performance testing may remain as the most robust method of validating engineering control performance, developments like wireless monitoring will certainly bring a more efficient and quicker method for obtaining operational data. [MGA1] [RA2]
[MGA1]Not sure I would wish to refer to this as ‘confirming equipment performance in situ’ Whilst the wireless monitoring does offer realtime operational data, this does not represent the equivalent in performance capability. I would like to see this re worded. Perhaps a message regarding – whilst realtime performance monitoring remains out of reach and the traditional containment performance testing remains the most robust method of validating engineering control performance, developments within this field will certainly bring a more efficient and quicker method in obtaining this data. (Feel free to re-word)