Assessing Particulate Containment Performance of Pharma Equipment

Summary

After a brief introduction to Pharmatronic by Vito Cerone, François Matthey drew the attention of the audience to a case study showing the value analysis for the replacement of two 30-year-old low and medium speed capsule filling machines (max. 140,000 capsules actual state, future state: 200,000 capsules @ 95% yield) based on a URS including product types and the evaluation of three suppliers for their offer and containment solutions (OEB3 according to ISPE guidelines) including specific personal protection measures such as glove boxes. To be on the safe side, the design target is set for the OEL (or bottom end of OEB, here 10 µg/m³) for the material of concern – usually the API.

As pointed by the Keynote Speaker Ramona Labatzke for every contained equipment not only the calculated OEL value (occupational exposure limit, µg/m³) should be addressed in the URS but also the CPT (containment performance target, µg/m³) should be defined for example for weighing and dispensing operations, so that the suppliers can match a safety level as CPL (containment performance limit, µg/m³) that should in case of initial and recurrent SMEPAC tests or newly APCPPE (Assessment of Particulate Containment Performance of Pharmaceutical Equipment) always be below the CPT.

There is also a need to harmonise testing (to EN 689) as compliance results need to be compared between sites or more stringent measurement strategies including test statistics if needed. From the external prevention we went to the client’s view and Jochen Niethammer pictured the CDMO view on extreme cumbersome measurements with both low CPT and LOQ (limit of quantitation) provided by products up to OEB5. In some cases, PPE was mandatory even though containment measures were built into the design. Then came Marco Bellentani’s contribution with the required CPT from the machine lifecycle supplier’s perspective depending on the interfaces or containment boundaries. It used to be that high potent APIs (OEB5) were mixed in a rather low percentage (<10%) with excipients where a dilution factor was considered for encapsulation (OEB4). As products become more potent, either due to higher API toxicity or API concentration, manufacturers can no longer rely on PPE and project execution will always require mock-up design, specific SMEPAC testing and the right containment strategy (provided by orthogonal solutions, for example) as the level of API emissions for a given energy input becomes more difficult to control. Last but not least Michael Maintok as OEB definitions may vary between guidelines (ISPE, etc.) and companies internal banding/standard, it is also a subjective interpretation of the calculated OEL.

Caveat: toxicologists may arrive at different OEL values because the calculation formula for the PDE leaves room for interpretation. It is therefore possible that the OEL values in different companies may differ, e.g. because the underlying studies were carried out with different animals or over different periods of time. In its publication of November 2020, the PIC/S stated that differences of up to a factor of 3 are generally acceptable. If the difference is less than a factor of 10, this difference should be justified, and if the OEL values differ by more than a factor of 10, the underlying studies should be reviewed in more detail.

The SMEPAC measurement that takes usually one to two days. It Measurement strategy has to be defined by an occupational hygienist with detailed knowledge.

«With the kind permission of the Aenova Group»

«With the kind permission of the Aenova Group»

Event „Performance Assessment of the Particulate Containment for Pharmaceutical Equipment- digital real time test methods“

Francois-Matthey-de-l’Endroit Group leader SGVC and Project Manager Pharmatronic AG Moderation and Experience feedback from a OEB3 filling line

Marco Bellentani Product Manager MG2

Capsule filling containment applications

Ramona Labatzke Occupational Hygienist Praevena and Jochen Niethammer Head of Technical Affairs Swiss Caps

Assessing the Particulate Containment Performance of Pharmaceutical Equipment

Michael Maintok Business Development Key Technologies Glatt GmbH

Containment Strategies in OSD Production

Glossar:

In some cases, the measured OEL is defined as a DEL (Design Exposure Limit), by analogy with the CPL.

The DEL (Design Exposure Limit) can be used at the macro level to direct the overall design of a facility/process, capturing matters such as layout, HVAC, people flows, material flows, etc. The CPT is used to define an engineering performance target (such as non-homogeneous particles in air) of an individual piece of equipment or process element.

As a working example, if the OEL of an API is 10 ug/m3, then one might design to a DEL of 10 µg/m3.

To weigh and dispense the 100% API, the CPT for the equipment used could be 10 µg/m3, but if the formulated API DP was to be produced as 50% API in excipient, then in principle the CPT for the equipment with the blended API could be 20 µg/m3.

This example is overly simplistic, but can illustrate the difference between DEL and CPT. In many cases the DEL and CPT will be the same. Also beware of trying to find subtle differences in DEL/CPT when a much bigger factor may be the actual level of containment/control achieved in reality.

While using such safety factors is common practise in a lot of engineering, it runs the risk of introducing very significant (and expensive) changes to the level of containment required to achieve the target

Designing to a specific OEL isn’t easy due to all the other factors that might affect emission levels such as dustiness, concentration, energy input, relative humidity etc.

Relying on experience of what works and understanding why, is perhaps the most important thing you can do.

It is important that the selection of the ‘Surrogate’ is appropriate for the CPT DEL. As a general rule, naproxen sodium (0.05 ng or 0.2 ng) is used for OEB 5 v/s Lactose/Mannitol (2 – 2.5 ng) or paracetamol (provided on courtesy by Weiss Technik).

Assessing Particulate Containment Performance of Pharma Equipment

Summary

Event „Performance Assessment of the Particulate Containment for Pharmaceutical Equipment- digital real time test methods“

Glossar:

Nicht nur Projekte … auch Verleih

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