Fire in a pharmaceutical plant

An explosion and a fire occurred in one of the units of a plant producing ingredients for the pharmaceutical industry. The unit affected was reducing an imide to an amine in presence catalysts. The reactor was nitrogen purged, because hydrogen was one of the reaction products.

On the day of the incident, the operation started 30 min before shift end. 15 minutes later the maximum was reached, and the operators started to cool the reactor to maintain a target temperature target temperature of approximately 65°C.
Despite the action, the reaction ran away: the temperature and the pressure rose in the vessel.
The operator nearest to the reactor smelled an unpleasant odour. Through the sight glass he saw a glow preceding the explosion.

Employees at 15 m distance perceive a blow. A flame projected through the workshop, other flames shot out from a joint and other reactor connections. Employees outside the building perceived a blow just before the explosion. A flame several metres high was visible for some seconds at the exit of a chimney connected with the reactor rupture disc (calibrated at 0.5 bar) that burst, allowing the decompression of the reactor.

The INITIATING CAUSE was the production of significant quantities of hydrogen formed by the runaway reaction and not absorbed by the reaction medium. The ignition of the gas may have been caused by static electricity in the reactor, a hot spot or the presence of diborane and water traces.

The equipment was essentially operated manually and required physical presence, in absence of remote control of the process. Part of the production process was not controlled by written instructions but let to the experience of the operators, among which there was a newcomer. In addition, the unit lacked the diagnostics required to monitor and control the reaction (flow metres, pressure gauges) and therefore also the automatic safety measures to prevent escalation and mitigate consequences.

The ROOT CAUSE was absence of a safety design and risk assessment , combined with failure to guarantee the correct operators knowledge.

chemical reactor.
burst disk

The synthesis operation had already been performed several times over 2 years.

DESCRIPTION OF THE PROCESS
The chemical reaction involved is the reduction of an imide compound to an amine compound in anhydrous medium in presence of (AlCl3) activated sodium tetrahydroborate.
The reaction is performed in an ether solution and the reactor is nitrogen purged.
The imide compound is introduced in the reactor via a flexible pipe connected with a mobile pneumatic dosing pump.
The operating procedure specifies that the reaction must be performed for at least 8 hours and that the temperature of the reaction medium must not exceed 65°C.

The following technical improvements have been made in the workshop: - measures on the parameters directly influencing he synthesis (substitution, automatic memorisation of the data, automatons with precise calibration) - check of all rupture discs - computerisation of the process control system (particularly of the alarm system) - installation of mobile dosing pumps with calibrated flows for specific use - control of the stirring speed - back-fitting of the electrical system - identification of the substances by means of colour codes - updating of the operating procedures and instructions - validating the equipment for every specific synthesis process. - upgrading of personnel training ( realisation of individual files, permanent training programme)

The were considerable hazards related to the reactions at the core of this production process. The incident revealed the absence of proper risk assessment and safe design. The consequences of failing of considering hazards in the design phase resulted in a unit which was operated manually, was not equipped with the measurements required to understand the process diagnostics, did not allowed remote-operation and lacked detailed written procedures. Under these circumstances, the knowledge and the experience of the personnel becomes critical. Also in this area, the management failed to address minimal safety requirements. Not all the personnel operating the reactor was well-trained and part of the process was not covered by written instructions.

(1) Specifically, the process instructions did not consider the flow regulations to be performed during transfer operations. These flow regulations were left to the know-how of the operators.
(2) The workers who were working at the reactor when the accident occurred were experienced except for the worker who performed the imide compound transfer for the first time. The unit worked discontinuously and was essentially operated manually.
(3) Two pumps with different flow capacity could be used for transfer operation, but no flow control meter was provided.
(4) There were no safety or devices to alert the operators in case of a drift of the operating parameters (high flow, high pressure in the reactor,)
(5) the unit was not equipped with remote control valves allowing the reactors to be isolated rapidly. The reactors could not be discharged rapidly, a "neutralisation of the reacting medium was impossible.
(6) the installation was not resilient, due to presence glass components.

The following technical improvements have been made in the workshop:
(1) measures on the parameters directly influencing he synthesis (substitution, automatic memorisation of the data, automatons with precise calibration)
(2) check of all rupture discs
(3) computerisation of the process control system (particularly of the alarm system)
(4) installation of mobile dosing pumps with calibrated flows for specific use
(5) control of the stirring speed - back-fitting of the electrical system
(6) identification of the substances by means of colour codes
(7) updating of the operating procedures and instructions
(8) validating the equipment for every specific synthesis process.
(9) upgrading of personnel training ( realisation of individual files, permanent training programme)