Microbes can damage your financial health

CIP/SIP (clean/sterilise in place) procedures, used to decontaminate equipment for the handling and manufacturing of biological solutions, have become increasingly important.

With the prospect of warnings from the UK based MHRA (Medicines and Healthcare products Regulatory Agency) and the possibility of patent applications being stopped and products removed from the shelf in the US by the FDA, ever more stringent controls are required to assure cGMP compliance. CIP cleaning is usually implemented through chemical action, based on a cycle of flushing, washing (sometimes steaming) and rinsing under a controlled recipe of time, temperature and chemical concentration. Bürkert, which has strengthened its presence in the ultra-hygiene sector through the development of a team of process specialists dubbed 'HandS' (Hygienic and Steam), has expertise applicable to processes designed to handle fluid or semi-fluid products, which must be produced in a very clean or sterile conditions. Considering the five P's of cGMP (People, Plant, Procedures, Products, Paperwork) the most effective and repeatable CIP operations are achieved by the application of considerable automation. For simple systems Bürkert's AirLINE can act as the brain of the system. Its decentralised intelligence has some real advantages: input from valves with feedback or process sensors and pneumatic outputs to actuate diaphragm valves. For larger systems AirLINE can be used as a modular entity in one simple but connected CIP skid, as users shift from centralised to dedicated CIP systems to reduce the risk of cross contamination. Piping, valves and sensors designed for CIP processes should never use threaded and flanged connections, as contaminants can accumulate in the threads or the space between flanges and gaskets. Ideally, the system would be completely welded, but tri-clamps and other "sanitary" connections are common. Process piping and vessels are normally constructed from stainless steel or equally corrosion-resistant material and must employ FDA approved materials for all wetted parts. Diaphragm valves are widely used in pharmaceutical processes and CIP applications to ensure drainability and cleanability, and through special block and welded designs guarantee a minimum of un-cleanable dead legs and pockets. The internal design is a simple weir over which closes an elastomeric or Teflon diaphragm. The actuation of the system can be manual or automatic through compressed air and the system can be delivered with feedback or can be made into a fully functional sterile control valve with onboard intelligence. Designing a system with diaphragm valves reduces the use of cleaning chemicals and shortens the cleaning cycle. They are used in the CIP delivery lines, the process lines and in the PW (Purified Water), WHP (Water Highly Purified) and WFI (water for injections) loops.

Required velocity Caustic and/or acid solutions and rinse water in the CIP piping systems in which diaphragm valves are found move at velocities greater than 1.5m/s (in the largest diameter piping to be cleaned). This minimum velocity changes within different facets of hygienic processing from dairy to pharmaceutical to beverages production but is defined as the velocity necessary to assure continuous movement of entrainments and purging of dead legs. Concentration of the CIP detergent is monitored by conductivity at two points; in the CIP make-up loop and on the CIP return line. The transmitter on the CIP return line, controls the CIP diaphragm divert valve (reuse or drain) and looks for the cleaning end-point. The wash solution volume is also measured by flow meters using methods from turbine to coriolis. The pressure is controlled by either variable speed drives or diaphragm control valves, and temperature is kept within tight tolerances through correctly sized heat exchanger equipment. Bürkert's latest developments in flow, conductivity, pressure and temperature measurement and control have added to its process valve expertise to position the company at the forefront of such CIP systems and applications. In pharmaceutical tanks, low-pressure spray balls deluge, cascade and soak the internal surfaces. Cleaning is achieved by chemical action and not a mechanical impingement action, but the pressure and flow should be controlled by a diaphragm control valve to eliminate variances. During the Factory Acceptance Test the effective-ness of spray balls is tested through a riboflavin coverage test to ensure that the internal surfaces of any vessels are thoroughly wetted. This does not ensure that the vessels will be thoroughly cleaned by the eventual CIP system but at least confirms chemical contact.

Concurrent engineering Nowadays the CIP system is inseparable from the process system and is usually engineered concurrently. A properly designed biopharmaceutical CIP system will use the minimum amount of water, chemicals and utilities, and produce the minimum amount of effluent. It will be safe, need minimum maintenance and should remove human error as far as possible. It will provide concrete documentation and ensure reproducibility while maintaining product quality and reducing turnround time between batches. Prudent pharmaceutical manufacturers constantly strive to ensure that their systems meet GMP standards through employing well-designed CIP. More commonly they demand complete solutions from engineering consultants and equipment suppliers to ensure hygiene and biological integrity . Manufacturing plants that ignore cGMP standards could seriously damage the health of their bottom line.