USP 精製水の循環管路の殺菌温度;65~80度に改訂

USP  Chapter <1231>WATER FOR PHARMACEUTICAL PURPOSESがup-dateされ、従来の循環殺菌用の温水の温度は、80度から65~80度に変更された。

 

5.3.1 THERMAL SANITIZATION

Thermal approaches to system sanitization include periodic or continuously circulating hot water and the use of steam. Temperatures of 65°–80° are most commonly used for thermal sanitization. Continuously recirculating water of at least 65° at the coldest location in the distribution system has also been used effectively in stainless steel distribution systems when attention is paid to uniformity and distribution of such self-sanitizing temperatures. These techniques are limited to systems that are compatible with the higher temperatures needed to achieve sanitization. Frequent use of thermal sanitization at appropriate temperatures should eliminate the need for other sanitization methods. The use of thermal methods at temperatures above 80° is contraindicated because it does not add to microbial control of the system or reduction of biofilm. Some methods (e.g., steam sanitizing, hot water circulation at temperatures ³100°) can be less effective or even destructive because of the need to eliminate condensate or manipulate system components, stress materials of construction, deform filters, and its adverse impact on instrumentation. Although thermal methods control biofilm development by either continuously inhibiting its growth or, in intermittent applications, by killing the microorganisms within developing biofilms, they are not effective in removing established biofilms. Killed but intact biofilms can become a nutrient source for rapid biofilm regrowth after the sanitizing conditions are removed or halted. In cases of infrequent thermal sanitizations that allow biofilm development between treatments, a combination of routine thermal treatment and periodic supplementation with chemical sanitization may be more effective. The more frequent the thermal sanitization, the more likely it is that biofilm re-development can be eliminated.

 

 

 

この変更に関するUSPのQ&Aで次のように解説している。

FAQs: Water for Pharmaceutical and Analytical Purposes

http://www.usp.org/frequently-asked-questions/water-pharmaceutical-and-analytical-purposes

19. In the new USP 1231 the recommended temperature in hot sanitizing has changed. The previous recommendation of at least 80°C has been lowered to 65-80°C. Now temperatures far in excess of 80°C are explicitly deemed inadvisable. Is this correct?

Yes. A temperature of 80˚C is very “forgiving” of cooler locations which can still be sanitized even with a 10-15˚C temperature loss as it penetrates throughout the system by convection and conduction, so it is very effective. Cooler temperatures (down to 65˚C) can also be used but is “unforgiving” of yet cooler locations such as outlet valves off of the main loop.  So such cooler locations must be flushed with this slightly cooler hot water in order to assure that all surfaces reach sanitizing temperatures greater than 60˚C. Unless systems are specifically designed for this, temperatures hotter than 80˚C can impact the longevity of system materials (e.g. gaskets and diaphragms). A temperature of 80˚C is well hot enough to kill the most heat resistant biofilm organisms that will colonize a water system (D value of about 5 milliseconds).

19.新しいUSP 1231では、熱殺菌の推奨温水温度が変わりました。以前の推奨は80°C以上であったが、改訂では65〜80°Cに引き下げられました。今では80℃を超える温水は推奨できない。これは正しいです?

はい。 80℃という温水温度は、対流と伝導によってシステム全体に到達するまで10〜15℃の温度損失があっても、温度が低い場所でのより低い温度の場所をも「許容」しているため、効果的な温度です。より低い温水温度(最低65℃)を用いて殺菌はできますが、メインループから外れたアウトレットバルブなどの温度が低い場所では「許容範囲外」です。したがって、すべての管路表面が60℃を超える殺菌温度に達することを保証するために、そのような冷却された箇所はこのやや低い温水温度で洗浄(循環)されなければなりません。システムがこの目的のために特別に設計されていない限り、80℃を超える温水温度は管路材料(ガスケットやダイヤフラムなど)の寿命に影響を与える可能性があります。 80℃の温水温度は、水系にコロニーを形成する最も耐熱性の高いバイオフィルム生物を死滅させるのに十分な温度です(D値約5ミリ秒)。

 

注;80℃を超える温水温度での循環殺菌することで。管路への負担が増加して、経済的にも負担であるが、管路の部材;特にOリング・ガスケットやダイヤフラムなどの寿命を短くするなど、保守への影響がみられるため、より精製水の維持を容易にするために今回の改定になった。

参考:

EPでは、温度の数値は、>75度とされている;

Q&A on production of water for injections by non-distillation methods – reverse osmosis and biofilms and control strategies

  1. What specific agents can be used as part of a control strategy?

Examples include sodium hypochlorite, hydrogen peroxide/peracetic acid solutions, sodium hydroxide. Appropriate contact times need to be established.

Additionally, preferred passivation chemistry methods can also be considered in the control strategy.

Ozonation should be also considered for loop and distribution systems for WFI water. The destruction of ozone can be done by UV irradiation/treatment.

Use of thermal sanitisation where possible should also be considered. Generally temperatures above 75°C should be utilised.

An approach that utilises a minimum of a double-edged approach should be considered, e.g. thermal sanitisation in conjunction with a chemical sanitisation at a set frequency based on robust risk assessment.

 

WHO GMP: WATER FOR PHARMACEUTICAL USEでは 70~80

6.3 System sanitization and bioburden control

Water treatment equipment, storage and distribution systems used for PW, HPW and WFI should be provided with features to control the proliferation of microbiological organisms during normal use, as well as techniques for sanitizing or sterilizing the system after intervention for maintenance or modification. The techniques employed should be considered during the design of the system and will be affected by the choice of materials. their performance proven during the commissioning and qualification activities.

Systems that operate and are maintained at elevated temperatures, in the range of 70–80 °C, are generally less susceptible to microbiological contamination than systems that are maintained at lower temperatures

 

局方;特に温度数値はない

○「無菌操作法による無菌医薬品の製造に関する指針」の改訂について (平成23年4月20日)