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Containment Engineering – A systematic approach to handle highly potent active ingredients and pathogens

Author Vishal Bundelee
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The need for the contained handling and processing of pharmaceutical materials and pathogens is on the rise due to the increased focus on health and safety and the growing interest in the development of High Potency Active Pharmaceutical Ingredients (HPAPIs). A wide range of containment equipment is available on the market to meet the processing and operational needs of development and manufacturing. Selecting suitable equipment, however, requires an in-depth understanding of containment aspects in order to avoid operational hazards and large capital investments resulting from an ‘oversizing’ approach.

In containment equipment selection the focus is on preventing the personnel from being exposed to hazardous substances. The equipment cannot, however, fully prevent exposure. It is thus important to ensure that exposure through containment equipment over the operational course of time is less than the product/pharmaceutical material exposure limit. The selection of suitable containment equipment requires a thorough understanding of product and equipment related exposure limits.

Product exposure limit

The product exposure limit is defined in terms of the occupational exposure limit (OEL), which is calculated based on the No Observable Effect Level (NOEL). The NOEL value is obtained by testing the pharmaceutical material on the species with daily dosage increases until the observable effect or reaction can be seen. The OEL can thus be calculated with the following formula:

occupational exposure limit

Figure 1. Containment is the isolation of a product or pharmaceutical materials from personnel and the environment or vice versa with the use of a physical barrier

Figure 1. Containment is the isolation of a product or pharmaceutical materials from personnel and the environment or vice versa with the use of a physical barrier

Figure 2. The appropriate containment system for each process is based on the quantity of materials, the occupation health hazard posed, the duration of the task and the physical form the handled materials.

Figure 2. The appropriate containment system for each process is based on the quantity of materials, the occupation health hazard posed, the duration of the task and the physical form the handled materials.

Equipment exposure limit

The exposure limit of the equipment can only be determined through air sampling procedures and then analysing the collected airborne particle samples. This amount is then divided by the volume of air sampled and the sampling time to give the Time Weighted Average (TWA) values of the exposure limit.

The TWA for evaluating pharmaceutical material is defined for 15 min as the Short Term Time Weighted Average (STTWA) and for 8 hours as the Long Term Time Weighted Average (LTTWA).

Correlation between OEL and TWA

Containment equipment needs be designed or selected in order to achieve LTTWA < OEL. The LTTWA can also be obtained from the STTWA considering the actual exposure time in the operational shifts. For example, the general industrial shift duration is 8 hours and the STTWA values for an exposure time of 15 min are available, then LTTWA based on STTWA can be calculated as follows.

LTTWA

Table 1: Isolation methods

Table 1: Isolation methods

A factor of 32 is used as there are four cycles of 15 minutes in an hour and the dilution factors is available data for STTWA for a 100% concentration of pharmaceutical material.

The containment equipment should as such be selected so that LTTWA is lower than the product-specific OEL.

Equipment evaluation

The selected equipment can be evaluated by considering a worst case scenario where LTTWA = OEL and then calculating the STTWArequired from the aforementioned formula as follows:

the STTWArequired

Methods of isolation and selection

As indicated earlier the OEL of pharmaceutical materials is the basis for the selection of the containment level required for processing the material. Thus, as the OEL limit shows a tendency towards lower values a more sophisticated level of isolation is required to carry out the safe processing of the pharmaceutical material.

The different types of isolation methods available are provided in Table 1. The appropriate isolation method is selected based on the criticality of the material handled or processed. In essence it is based on the OEL, the physical characteristics of the materials, the quantity handled and the duration of pharmaceutical material processing. See Figure 2.

Proper selection and meeting owner’s requirements

HPAPI is currently one of the fastest growing segments in the pharmaceutical industry, with a growth rate of 8 to 10 per cent. This high growth rate is attributed to their application in the formulation of high potent drugs used to combat some of the severest diseases. The market opportunities and treatment capabilities have resulted in the increased interest shown by pharmaceutical companies in investing in the development and manufacturing of HPAPI.

Handling these materials, however, requires sophisticated isolation methods, which demands an understanding of the basic concepts of containment engineering. This understanding assists in the proper selection of the suitable isolation method thereby meeting the operational and financial requirements of the owner.

The selection of suitable containment equipment requires a thorough understanding of product and equipment related exposure limits.

 

The original text was published in our 1/2014 Top Engineer magazine

 

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Vishal Bundelee

B.Sc. , Chemical Engineering - Vishal Bundele works as Executive Engineer, Process at Elomatic Pharmalab Consulting & Engineering Pvt Ltd in Mumbai, India. He has strong know-how in pharmaceutical project phases such as installation, commissioning, qualification and validation. At Elomatic he has, among others, been involved in the re-validation of the oncology product manufacturing (small volume parentals) facility at Mylan Laboratories Ltd. in Vishakhapatnam.

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