NEWSLETTER July 2011
Safe handling of potent and highly potent active pharmaceutical ingredients Potent and highly potent Active Pharmaceutical Ingredients (API) have the potential to cause serious health effects in workers at very low airborne concentrations. The use of containment equipment as part of a systematic approach to potent compound safety is advised to control worker exposure. Based on toxicological evaluations, APIs can be placed into control bands depending on their potency. In general, API’s are classified using occupational exposure limit (OEL) as a classification scale.
Definition of OEL OEL is the airborne concentration of a compound to which nearly all workers can be repeatedly be exposed 8 hours a day, 40 hours a week, without adverse effects.
NOEL * G OEL = F *V OEL — Occupational Exposure Limit mg /m3 OEB — Occupational Exposure Band mg/m3 DEL — Design Exposure Limit mg/m3 NOEL — No Observation Effect Level mg/kg*day G — Body mass 50 kg (female)/75kg (male) V — Breathing air volume in 8 hours m3/day ADI — Acceptable Daily Intake (=NOEL*G/F) mg/day F — Assessment factor © Lonza Ltd., Basel, 2007
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Newsletter - July 2011
OEB at Lonza Lonza
Classification followed by a containment strategy is the first step in a systematic approach to ensure worker safety when handling potent and highly potent APIs
Containment Strategy Using a simplified selection criteria working through the following stages (see picture below)
Containment ContainmentStrategy Strategy11 Control General Ventilation
Containment Containment Strategy Strategy 22 Airflow Booth Technology
ContainmentStrategy Strategy33 Containment Barrier Isolation Technology
ContainmentStrategy Strategy44 Containment
ContainmentStrategy Strategy55 Containment
Direct/Closed Connection within Barrier Isolation
Fully Automated system - No operator input
It is important to focus primarily on facility design, isolation and containment. As a second layer of protection personal protective equipment and personnel controls must be designed and implemented as well. 2
Newsletter - July 2011
CONTAINMENT DEVICE SELECTION Selection of containment equipment generally has to include at least the following elements: • Step by step analysis of the entire process to produce a detailed list of all tasks involved • Setting of a containment performance target (CPT CPT). CPT • Specifying and selecting containment equipment based on the task list and CPT. CPT • Verifying containment performance at the factory acceptance test (FAT FAT) SAT) FAT and the site acceptance test (SAT SAT • Assessing occupational exposure to workers during actual operations involving the API The step by step analysis must be sufficiently detailed to identify all aspects of the process that may be encountered operationally. Examples of important issues that are often missed during this analysis are contained transfer of waste, decontamination of materials and equipment prior to transferring out of containment.
CONTAINMENT DEVICES A wide range of devices are available which allow contained operations to be carried out during chemical production of potent and highly potent APIs and during the formulation of pharmaceutical products containing these APIs.
Butterfly split valve
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Butterfly split valve
Butterfly split valve
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Charging Bags
Liner system with O ring canister
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Continuous liner system
High containment system
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Glove box isolator
Flexible isolator
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Discharge Big Bag into the dryer
View into the isolator working room with balance
© Lonza Ltd., Basel, 2010
© Lonza Ltd., Basel, 2007
Charge big bag
Charge big bag
© Lonza Ltd., Basel, 2007
© Lonza Ltd., Basel, 2007
Sampling of spherical dryer
Discharging big bag into dryer
© Lonza Ltd., Basel, 2007
© Lonza Ltd., Basel, 2007
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Lonza Engineering Ltd Lonza Engineering is a subsidiary of Lonza Group Ltd and provides customer oriented services with a professional, experienced and highly motivated engineering team. We have more than 15 years of successful project management experience in China which makes us a perfect partner for the chemical, pharmaceutical and biopharmaceutical industry. A broad range of services with a project reference list underlining our capabilities is available upon request. © Lonza Ltd., Basel, 2007
Operation in glove box
Lonza Engineering has successfully managed multiple and complex projects such as continuous operating plants for the production of food and feed additives as well as active pharmaceutical ingredient plants including waste gas and liquid waste treatment facilities. The management team of the new company consists of current Lonza employees from Switzerland and China.
Contacts
© Lonza Ltd., Basel, 2007
Filtration
Lonza Engineering Ltd Muenchensteinerstrasse 38, CH-4002 Basel, Switzerland Tel: +41 61 316 8606 Fax: +41 61 316 9606 Email:
[email protected] [email protected]
In this context, Lonza Engineering’s service could include:
Design service and consultancy Risk analysis Process simulation Support procurement process Project management
Pls. discuss your requirements with our experts, we would be very happy to offer our support.
Website: http://www.lonza.com/engineering
Lonza Guangzhou Engineering & Consulting Co. Ltd 68, Huanggedadao Bei, Nansha district, Guangzhou, 511455, Guangdong Province, China Tel: +86 20 3497 1118 +86 20 3497 3888 ext.2366 Fax: +86 20 3497 2288 Email:
[email protected] [email protected] Website: http://www.lonza.com/engineering
An extensive service list is available on our website: http://www.lonza.com/engineering
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