High-potent drugs
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High-potent drugs
The increased likelihood of rapid growth of the market for high-potent drugs, including anticancer drugs, has heightened public expectations for advanced technology applicable to manufacturing equipment suitable for handling highly active materials and to the containment of those materials.
Daito has the Seventh and Eighth Formulation Buildings, which are dedicated to manufacturing high-potent drugs, and the High-potent Drug R&D Center, which develops and analyzes high-potent drugs and manufactures investigational medicinal products (IMPs) and other products in small amounts. The Company is capable of manufacturing products in a wide range of scales, from a small scale (1 to 10 kg per lot) to a large scale (50 to 100 kg per lot).
In December 2020, the second line in the Eighth Formulation Building was completed, enabling us to meet demand for manufacturing products in a larger amount.
Management of Highly Active Materials
Measures to prevent excessive occupational exposure
Unlike ordinary formulation products, high-potent drugs are manufactured at special manufacturing facilities. The most important requirement in all stages is to contain highly active materials in order to prevent excessive occupational exposure to them and environmental contamination.
To fulfill this requirement, Daito has devised and implemented measures to contain highly active materials in line with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines and the latest American and European guidelines. These measures are based on a combination of physical elements (manufacturing equipment and air-control equipment) and behavioral elements (such as changing clothes appropriately and working in a correct way). For example, containment in the manufacturing area is achieved by making the air pressure in the manufacturing chambers lower than all their surroundings or keeping the air pressure in these chambers negative and that in their surroundings positive.
In a weighing chamber, where exposure risks are high, substances are weighed and compounded in an isolator, and the compounds are put into a special airtight container to prevent them from being scattered.
Staff working in development, analysis and other areas wear safety equipment and operate correctly so that their bodies will not be affected by hazardous substances. In addition, when testing can be carried out with a trace of substances at basic-research and other stages, advanced instruments are used to analyze ingredients or products. Each facility is zoned into multiple areas according to the level of exposure risks assessed based on the amount of high-potent substances handled there and the likelihood of them being scattered. A high level of containment is achieved by creating barrier zones around zones with high exposure risks.
Before entering the manufacturing area, everyone is required to change into dust-free garments in the locker room, wash their hands, wear gloves, a mask and special shoes, and remove dust from the entire body using a sticky roller. Furthermore, before entering an area that needs a higher level of containment, everyone must wear a protective gown over the dust-free garments and then get equipped with a self-contained breathing apparatus. The manufacturing area is protected by two airlocks, one for entry and the other for exit.
There are various rules and manuals on entry and exit, formulated to prevent cross-contamination. Once staff enter a facility dedicated to handling highly active materials, they are not allowed to enter facilities for ordinary drugs on the same day. The interior environment of each facility is optimally maintained in terms of pressure and temperature so that the Company will be able to research, develop and manufacture safe, high-quality high-potent drugs.
Measures against environmental pollution
In manufacturing and R&D facilities, containment is ensured by keeping the air pressure in high-risk zones negative and achieving primary containment with manufacturing equipment and secondary containment with air-control equipment.
After use, the isolator is washed inside with purified water, which is then drained through a drain line dedicated to hazardous wastewater leading to a dedicated tank. After being stored in the tank, the wastewater is finally burned and made harmless.
To assess the effectiveness of the containment of highly active materials, we conduct swab tests* on vents, as well as floors, doorknobs and other things that staff often touch directly or indirectly, in line with applicable in-house rules.
- Tests conducted to quantitatively measure the level of residues swabbed up directly from the surfaces of instruments
What are highly active materials?
Materials that can have strong medicinal effects on human bodies even in a small amount, such as some kinds of steroids and anticancer drugs, and toxic and other harmful materials
Source: Website of the Japan Society of Pharmaceutical Machinery and Engineering
- Highly pharmacologically active substances (biologically active at approximately 15 μg or less per kg of body weight/therapeutic dose 1 mg or less)
- Substances with an occupational exposure limit (OEL) of less than 10 μg per cubic meter of air
- Carcinogens, teratogens, reproductive and developmental toxicants, substances that are organ toxic even in a small amount, genotoxicants, etc.
- Occupational exposure limit (OEL): Upper limit on the acceptable concentration of a hazardous substance in workplace air, which is defined to restrict workers’ level of exposure from the perspective of the protection of their health
