Sparkling clean and easy to swallow

Pierre Fabre Médicament Production is the second largest independent pharmaceutical laboratory in France. The company produces a wide variety of medical products in its Gien (Loiret) factory, including tablets, sugar-coated pills, capsules, sachets, solutions and drinkable ampoules, creams and ointments. The liquid dosage production unit has a variety of tanks, mixers, pumps and transfer valves. This equipment is cleaned with a cleaning-in-place (CIP) station that has a fresh purified water tank, a return purified water tank, an acid solution tank and a sodium solution tank. Two cleaning lines contain disinfectant.

In 2008, the plant faced a challenge. The control system was getting old. The plant needed a reliable, expandable control system to control the CIP and manufacturing processes and ensure that data processing conformed to US Food and Drug Administration (FDA) requirements (21 CFR Part 11). Hakim Bennouna, instrumentation, automation and process maintenance manager at Pierre Fabre Médicament Production, says he opted for a Simatic-based solution because of the availability, robustness and stability of Siemens’ automated systems.

The new control solution handles both the CIP and manufacturing processes. The CIP station has seven recipes and the manufacturing process has 65. These recipes are stored within the operator station and sent to the programmable logic controller (PLC) as needed. Operation begins with a rinse using return water. Several cleaning stages follow, with acid for stripping, sodium to neutralise the acid, disinfectant and a final rinse with fresh water. Simatic S7-300 controllers open the fluid valves (hot and cold purified water, alcohol) and a Simatic S7-1200 controller powers pumps supplying the sodium and acid.

The Siemens architecture includes a Simatic PCS 7 box; a Profinet network for inter-controller communication; a Simatic S7-1212C controller, which controls acid, sodium and disinfectant; a Simatic S7-300 controller with a 315-2 PN/DP CPU for the cold purified water loop; and a Simatic S7-300 controller with a 317-2 PN/DP CPU for the hot purified water loop, which supplies the freshwater tank and the premix and mixing tanks. The system is completed with a Simatic S7-300 controller with a 315-2 PN/DP CPU for drawing alcohol. This architecture is complemented by a communication system that ensures correct management of all processes, from CIP to drug production.

Batch processes used to be managed manually via a non-automated system in Fortran. Today, Simatic Batch within the Simatic PCS 7 Box controls production and CIP and automates recipe use. Operators have experienced a genuine revolution in their working routines.

“The real challenge was not only to ensure that operators adhered to the automated system, but also to familiarise them with operating an automated facility,” says Bennouna. “A further challenge was commissioning. We had four months to develop the system and only two weeks to put it into service!”

Operators adapted very quickly, following a four-hour training session. “Soon, certain operators will even be able to change manufacturing or cleaning recipe parameters themselves,” says Gil Soustre, who is in charge of liquid-dosage-form production. The automated system makes it easier for operators to become multidisciplinary. An operator in charge of manufacturing might also oversee automatic cleaning processes. In addition, the plant’s hardware configuration enables operators to use any mixer or send product through any piping system. Productivity has increased.

“The time for routine cleaning used to be 80 minutes. It is now only 60 minutes,” says Soustre. “The gain in productivity adds up to four hours per day.”

Traceability is also improved, thanks to the multiple recordings made of lead times, conductivity and temperature. Cleaning quality is better than before. After passing through the cleaned equipment, rinse water has a conductivity of 0.3 to 2.80 µS, which corresponds to chemically pure water. This proves all the stripping, detergent and disinfectant agents have been eliminated.