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It is also intended to help ensure that APIs meet the quality and purity characteristics that they purport, or are represented, to possess. The term manufacturing is defined to include all operations of receipt of materials, production, packaging, repackaging, labeling, relabeling, quality control, release, storage and distribution of APIs and the related controls. The terms current good manufacturing practices and good manufacturing practices are equivalent. The company should designate and document the rationale for the point at which production of the API begins. For synthetic processes, this is known as the point at which API starting materials are entered into the process. For other processes (e.g., fermentation, extraction, purification), this rationale should be established on a case-by-case basis. From this point on, appropriate GMP guidance should be applied to these intermediate and/or API manufacturing steps. This would include the validation of critical process steps determined to impact the quality of the API.

Construction materials

Construction materials for equipment coming in contact with food (including associated adhesives) must be food grade (FDA-approved or national equivalent). Selection of construction material depends upon the dry materials, method of cleaning and cleaning agents to be used.


Hygienic dry materials handling is best conducted with product contact surfaces of stainless steel. Suitable grades are SS 304, 304L (EN 1.4301/1.4306) and SS 316, 316L (EN 1.4401/1.4404). Aluminum and aluminum alloys (coated and non-coated) might also be used as dry material contact surfaces where only dry cleaning is applied.


Plastics (e.g Polycarbonate, PEEK, PVDF, PA and PTFE) and elastomers (e.g. NBR, Viton, Silicon, FEPsilicon) may be used, but contact should be limited where the dry material is abrasive. These materials must retain their original surface condition when exposed to the processing and cleaning conditions. Fabrics and non-metallic filter materials used in connection with the cleaning of air involved in dry materials handling systems must be non-toxic, cleanable, and not impart contaminating smell to the dry material. Nonmetallic surfaces can create electrostatic charges on the material, which can be problematic.


Hygienic design of valves

Every process plant is equipped with valves. Depending on system size, hundreds, even thousands of valves can be found in piping matrices in liquid-processing plants. Valves fulfill numerous functions in process plants: shut-off and opening of product routes, changeover, flow and pressure control, protection against excessive or insufficient pressure, and protection against the intermixing of incompatible media at intersection points in pipes.
The quality of the valve may have a considerable influence on the quality of the production process and, hence, the product itself. Hygienic deficiencies resulting from valve design may result in microbiological hazards in the production of food products. The risk for the product increases with each valve installed in the process plant. Therefore, it must be ensured that valves for food-processing use comply strictly with hygienic requirements.

Surface roughness has a significant influence on cleanability. The greater the surface roughness, the llonger the required cleaning time. In principle, any treatment of product-contact surfaces should result in a surface roughness value of Ra <= 0,8 μm. A rougher surface may be acceptable, but the deviating surface roughness must be dearly specified. (In the beverage industry. a roughness of Ra = 1,6 μm is usually acceptable.)


Hygienic design criteria

Dry materials handling must take into account the possibility for material lump formation, creation of dust explosion conditions, high moisture deposit formation in the presence of hot air, and material remaining in the equipment after plant shutdown (even if a degree of selfemptying is achieved).

Product contact surfaces

Product contact surfaces should be smooth and resistant against dry material contact and also against liquid chemicals used in wet cleaning. Product contact surfaces therefore should be free of crevices, pitting, pinholes and any hairline cracking that can cause material penetration and cleaning difficulties. A roughness standard of Ra<0.8 mm is recommended where there is a risk of microbial growth associated with high moisture content in the dry material or wet cleaning. In order to carry out a dry cleaning operation, contact surfaces should be fully accessible for safe manual cleaning and inspection. For a hygienic wet cleaning operation, contact surfaces should not be horizontal, but have a slight slope to facilitate drainage of cleaning solutions. The possibility for product contact on sharp internal corners (r<6 mm) and recesses, etc., where dry material can accumulate, should be avoided. Windows and inspection ports mounted in product contact surfaces should be flush with the surrounding surfaces to minimise dry material build-up. When using nonmetallic materials as contact surfaces, the porosity of the materials should be investigated with regard to ease of cleanability.


Welds must be accomplished in a way that avoids susceptibility to accumulation of dry material and localised corrosion. It is important to ensure that the metallurgical properties of the weld material are as close as possible to the parent metal. General criteria for welding are described in the EHEDG Doc 9 (EHEDG, 1993b) ‘‘Welding stainless steel to meet hygienic requirements’’. Intermittent (spot) welding of dry product contact surfaces is in principle not acceptable. Normally, the surface roughness of welds does not meet the recommended figure of Ra 0.8 mm. The cleanability of these parts in relation to the actual dry material being handled should be validated.

Static seals (gaskets)for duct and flange connections

Static seals should be of an elastic material, have a non-porous surface and be cleanable. Static seals should be clean before assembly and the possibility for penetration of dry material into the gasket or seal during equipment operation should be avoided. PTFE can be used as a static seal in combination with an elastomer (food grade, FDA-approved or national equivalent). The PTFE should be of high-density resilient quality. Metal-to-metal contact duct assemblies and paper-type gaskets between flanges can be applied where a plant operates at atmospheric pressure and requires no wet cleaning. Inflatable seals, e.g. for valves (Fig. 1) or around access doors and operable inspection ports should be used to prevent dry material build-up around the mounting frames.


Welding stainless steel to meet hygienic requirements

Inadequate welding can compromise product safety in an otherwise hygienically designed food-processing plant. This paper summarizes guidelines prepared by the Design Principles subgroup of the European Hygienic Equipment Design Group (EHEDG) to increase awareness of the importance of and techniques required to ensure the production of hygienically acceptable welds. This isthetenth in a series of articles featuring the EHEDG to be published in Trends in Food Science & Technology. The EHEDG is an independent consortium formed todevelop guidelines and test methods for the safe and hygienic processing of food. The group includes representatives from research institutes, the food industry, equipment manufacturers and government organizations in Europe.

Incorrect penetration of the weld can be caused by poor welding technique (e.g. poor control of the welding
current) or incorrect parameters. Ideally, the weld metal should exactly fill the joint and remain flush with the surface. Underpenetration leaves a crevice at the joint, which is a hygienic problem both in vessels and pipework; excessive overpenetration can also hold up product in pipework, although the excess can be removed in vessels by grinding. Surface porosity, or excessive inclusions that may become detached thereby creating surface porosity, can trap product and be difficult to clean. Lack of full fusion of the weld metal in the joint to the parent metal results in crevice formation at the interface between weld and plate [associated mainly with MIG (metal inert gas) welding].

Inadequate inert gas shielding (generally nitrogen or argon based) of the reverse surface, when welds are completed from one side only (e.g. pipework welds), results in a roughened weld and heat-affected zone; this promotes the adhesion of soiling and is difficult to clean. 

Many welding processes are in common use, but only a few can deliver welds of hygienic quality free from the types of defects outlined above. The most appropriate welding process is the gas tungsten arc welding (GTAW) process, commonly referred to as TIG (tungsten inert gas) welding. In this process, an arc is struck between a tungsten electrode shrouded with an inert gas and the workpiece. There is often an external feed of filler wire to the joint. although thin sections «3 mm) can be joined without filler wire ('autogenous' welds). The filler wire is usually of the same composition as the parent plate, and special consideration is required if mixed metals are involved. In some cases it may be desirable to use a higher-alloy filler wire.
The TIG process can be used for pipework and for thin sheet up to -4 mm thick; a manual metal arc process, followed by post-weld grinding, would more likely be used for thick sections. For many hygienic applications, thin-walled vessels and pipes are commonly used.


About us

Over the years Separeco has created a supply technology chain that allowed to fully develop the technology applied to supercritical fluids starting from scientific knowledge to industrial plant construction, in particular through the use of supercritical CO2 in the pharmaceutical, cosmetic, nutraceutical, food, healthy food. The name is “Super Critical Fluid Network”, (SCFN).

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