Humidity control for GMP compliant production
通过湿度控制实现GMP合规生产
Martin Ginty, 蒙特全球制药行业总监
Martin Ginty, Pharmaceutical industry director of Munters
郑丽丽,蒙特中国制药行业应用工程师
Lili Zheng,Pharmaceutical industry application engineer of Munters
摘要/ Abstract:
GMP compliance in pharmaceutical manufacturing requires that any process, person, environment or equipment with direct impact on the quality and safety of the product being produced must operate within specified limits. Humidity can be a problem, and can result in non-compliant production,resulting in a series of problems. According to the temperature and humidity requirements of each production area, we can use different psychrometrics and humidity control methods to control the temperature and humidity in each production area within a reasonable range, so as to ensure that each production link can meet the requirements of GMP operating environment. With over 60 years of experience in pharmaceutical and other areas of manufacturing, Munters can provide desiccant dehumidification solutions as well as expertise and support to ensure your production remains GMP compliant.
药品生产质量管理规范(GMP)要求对于药品的质量和安全性有直接影响的工艺、人员、环境或设备必须在指定范围内进行操作。如果湿度不满足生产工艺的要求,进而会造成生产不合规的情况,产生一系列的问题。我们可以根据各个生产区的温湿度要求,采用不同的焓湿和湿度控制方法,将各生产区的温湿度控制在合理的范围之内,从而保证各个生产环节能够满足GMP的操作环境要求。凭借60多年的制药行业和其他领域生产经验,蒙特可以提供干燥除湿解决方案以及相关专业知识和支持,确保您的生产符合GMP规定。
关键字/Key Words:
GMP 生产工艺 温湿度要求 焓湿和湿度控制 蒙特 干燥除湿解决方案
GMP production process Temperature and humidity requirements Psychrometrics and humidity control Munters desiccant dehumidification solutions
GMP compliance in pharmaceutical manufacturing requires that any process, person, environment or equipment with direct impact on the quality and safety of the product being produced must operate within specified limits. These limits are controlled by the manufacturing team, with countermeasures available in the event of a problem occurring. Any other indirect production or storage processes must also be assessed for possible risk impact.
Humidity can be a problem, and can result in non-compliant production. Uncontrolled humidity levels can affect production processes and lead to producing out of specification products.
Some common issues that can arise from poor humidity control are:
The relationship between relative humidity (RH%) and air temperature is important, variations in temperature will also affect RH%. For example, temperature drops or cold surfaces can result in condensation.
Humidity in manufacturing areas
Look at the following typical conditions found in areas related to solid dosage production:
When RH% levels are correctly maintained for the designated process areas then humidity related issues are unlikely to occur, either to the product or the production equipment itself. The required RH% values for any given process are depend on:
{C}o {C}The materials being used (APIs, excipients).
{C}o {C}The manufacturing space, location, climate, etc.
{C}o {C}Standard Operating Procedures.
{C}o {C}GMP specified values which may be influenced by other factors.
Therefore, in all areas of production, humidity levels should always be carefully considered for optimal product quality.
Ask yourself:
{C}o {C}Do the RH% levels within my facility exceed GMP specified values at any time?
{C}o {C}If they do, for how long? What is the recovery time to return to the specified value?
{C}o {C}What is the impact of this and do I need to react to this?
{C}o {C}Is recovery time fixed or variable?
… and maybe you experiencing moisture related production or quality problems:
{C}o {C}The flow of API and excipients is not as expected.
{C}o {C}Variations when weighing of batches of raw materials or finished product that could be caused by fluctuations in water content.
{C}o {C}Signs of clogging, caking or other obstructions in silos, bins, pneumatic transport pipework and process equipment?
{C}o {C}Consideration should be given to moisture-permeable containers for packaging.
{C}o {C}APIs and excipients that are prone to hydrolytic degradation.
Even when all of these factors are taken into account, perhaps you need to go right back to the start and ask, “How was the RH% level for production and storage processes determined in the R&D phase?”
Storage and Warehousing
Deviations from the claimed temperature and humidity conditions must be minimised, controlled and documented. Unfortunately, temperature and humidity excursions are almost inevitable, but automated control of HVAC and humidity control systems will improve response and recovery, and can also provide historical and trend data to track these excursions.
The effects temperature or humidity deviations on every item held in storage need to be considered. This can be a daunting task for warehouses to containing hundreds or maybe even thousands of different inventory items, with more new items coming in future. The impact assessment therefore has the potential to become an enormous task.
It is easier to ensure temperature and humidity are controlled within defined limits, supported by automatically generated logs.
Psychrometrics and humidity control
There are different ways to try to control humidity.
Using outdoor air for ventilation - Ventilation air must have a lower moisture content than the air within the building to be effective and is therefore at the mercy of changing weather and seasonal conditions. So, let’s ignore using untreated outdoor air because of its variability and look at other ways to treat the air either entering or already within the building.
Heating – This lowers the relative humidity but not the absolute humidity, there is still the same mass of water vapour and the dewpoint is unchanged. This might be a reasonable approach if you need to heat the area for comfort, but it can be relatively expensive.
Cooling– Using cooling coils to reduce the air temperature below its dewpoint will lower the RH% after cold air is re-heated, and it will also reduce absolute humidity. However, efficiency falls significantly at air temperatures below 10°C. In addition to this, condensation on the cooling coils can lead to corrosion and the wet conditions are a good breeding ground for bacteria and mould.
Desiccant dehumidification – This reduces both relative and absolute humidity, and also reduces dew-point without being temperature sensitive (operating range is between +40°C to -40°C), while the lower airflows result in energy savings. Multiple energy sources are possible e.g. gas, steam, LPHW, etc. so available utilities and waste heat can be used. The system runs dry which reduces the possibility of microbial growth and maintenance arising from wet conditions, which can also translate to longer equipment life. Furthermore, this form of humidity control can dry down to a -70°C dewpoint which may be required for sensitive APIs.
In closing
With over 60 years of experience in pharmaceutical and other areas of manufacturing, Munters can provide desiccant dehumidification solutions as well as expertise and support to ensure your production remains GMP compliant. We are able to provide scalable systems that can be deployed in R&D, pilot plant and full scale manufacturing areas, ensuring that your investments of time and effort can be leveraged as you move from limited production for testing and trials through to full production.