A new version of GMP ultimate interpretation (2)


When producing non-sterile API, we can set the drinking water pipe in the D clean zone? For instance, in the D clean workshop (non sterile apis with baking bag), the water used in restroom, sanitary ware wash room, laundry room (including clean clothes cleaning) , first-used water for containers, all of there having the drinking water pipe. The water is used for hand-washing, wall and floor cleaning, shoes and clothes washing. All the equipment and container adopt the purified water and purified clean water pipe. Is this setting in line with the 2010 pharmaceutical GMP requirements or is it necessary to dismantle the setting before applying for the version of the drug GMP certification in 2010?

Explanation: attention, no sterile drugs are adopting CNC set in the world , usually, the uniform of this zone does not use anti-static cloth but a cloth of same material while different color as the outer packing zone. This kind of zone uniform pays attention to the cleaning of the particles in the water, whose hazard is acceptable. So as long as the setting is in line with the GMP, it’s unnecessary to dismantle the drinking water pipe. the water can be used for hand-washing in dressing room, container washing, wall and floor cleaning, shoes and clothes washing.

Does the installed hepa filter need a leaking detection on a regular basis after leakage acceptance?

Explanation: Internationally, A, B, C, D is for aseptic drug. SPE HVAC 2009 calls the sterile drugs CNY(page 11, table 1.1 , level standard comparison table shows the CNC = Controlled Not Classified). In another word, don't take the D level of sterile drugs simply apply to non sterile drug production for the sake of hazard consideration. In the design of HVAC, ISPE HVAC 2009 refers that the level of production of clean areas of non sterile should be static level 100000. And Static class of 100000 air conditioning system design is usually the HEPA filter (HEPA) installed inside a modular air conditioning units. Installing the hepa filter on the exhaust side of the unit and the high efficiency filter in terminal is also acceptable for the reason to meet the requirement of level and prevent pollution, which is quite different from the traditional way of domestic enterprises. If there is a basis of risk assessment, not using a heap filter is reasonable but if use the filter level should not lower than F-8(filtration efficiency not less than 95%).

High efficiency particulate air (HEPA) filter is normally installed in the modular air conditioning units. Meanwhile, for the sake of risk assessment, some key parts need terminal HEPA filter individually.

According to above data, we can comprehend the requirements of the 2010 version of GMP (Good Manufacturing Practice):

The non-sterile drug Grade D is just acknowledged for reference. For instance, when HEPA filter is used in design, at the end of the installation project, it is usually used for leak detection, but not of periodical.

Without the HEPA filter, the project could be operated as well; but in this case, there would be no leak detection at all.

The production of oral liquid employs the principle of "control the indefinite-grade areas ", which can better reflect the idea of risk management.

In addition, as you go through the tutorial in International Society for Pharmaceutical Engineering (ISPE), in section 3.7 (Page 54) Oral Solid Dosage (Non-Potent Compounds) and section 3.8 (Page 57) Oral Solid Dosage (Potent Compounds), it makes further explanations on the design requirements with figure and words. The non-sterile drugs ought to be produced according to these requirements.

Can drinking water pipe be installed in the Grade D clear band where the non-sterile drugs are produced? For example, in one Grade D clear band workshop, drinking water pipes are everywhere, including water for hand washing, sanitary, clothes and other cleaning tools. The drinking water is mainly used for washing hands, cleaning walls and floors, shoes and tools. All these things ask for purified water in cleaning, so that in equipment spots only drinking water pipe can be installed.

Here comes the question: Is this setting compliance with rules (the 2010 version of GMP)? Otherwise, before applying for certificate, must we remove all the pipes?

Explanation: Attention please, the CNC setting is put to use in the non-sterile drugs all over the world (see also Question 606), thus in this area the labor suits do not use anti-static cloth, but using the same material as those in the outer packing area, only color differs. This kind of working suits would care more about the particle in the cleaning water, yet the risk could be avoided usually. So the problem below can be explained, that as long as the purified water don’t violate GMP, there’s no need to remove the water pipes. The water can be used in washing hands, cleaning tools, sanitary fittings, walls and floors, shoes and clothes.