Pharmaceutical manufacturing relies heavily on pure steam, particularly in sterile pharmaceutical manufacturing. Pure steam is largely used to sterilize apparel, pipelines and all components, as well as directly and indirectly contacting product contact surfaces; therefore, it must meet exacting standards.
The establishment of a validation program that is strong enough to provide that the pure steam system will produce and deliver steam of acceptable quality for ALL operating conditions is necessary to assure that pure steam consistently meets the specified standards. Regulatory agencies emphasize this under their Good Manufacturing Practice requirements and it is one of the major areas of focus during an inspection.
Unlike regular plant steam, Pure Steam has a wide range of applications including where high levels of purity are required, such as:
- Poor or ineffective sterilization
- Cold spots within the sterilizing unit
- Inefficient or incomplete sterilization
- Water build-up within the sterilizing unit
1. Water supply (PW or WFI)
2. Steam generator
3. Piping to distribute steam
4. Collection method for condensate from the pure steam system
It is essential that all components are designed and maintained correctly in order to uphold the integrity of the overall system.
- Evaluation of system design
- Evaluation of materials selection
- Verification of compliance with hygienic design principles
- Verification of the installation of equipment
- Verification of the piping and instrumentation
- Review of the associated documentation
- Functional testing of control systems
- Verification of alarm functions
- Verification of operating parameters
- Samples will be collected from various locations within the system
- Tested for non-condensable gases, dryness and superheat
- Tested via chemical and microbiological methods
Open the cap of the bottle and fill the bottle with steam condensate by holding the bottle in the holder. Gloves should wear into the hands while sampling the pure steam. Tighten the cap of the bottle and mark with the sampling information. If the sample is not analyzed within 2 hours of sampling, store the sample at 2-8 °C.
1. Non-condensable Gases: Non-condensable gases are air and carbon dioxide those do not condense with the steam. These are generated due to their presence in the purified water that continuously circulates in the water distribution system. Non-condensable gases should not be more than 3.5%.
2. Steam Dryness Value: Dry steam has more energy than the wet steam. Wet steam has water with it and does not have heat energy as dry steam. Dryness of steam is determined by the latent heat. Dryness of the pure steam should not be less than 90%. High moisture content can cause the loss in energy of steam and that may cause the longer sterilization time.
3. pH: Steam condensate is analyzed for pH value at 25 ° C. It should be between 5-7.
4. Conductivity: Conductivity should be tested with calibrated conductivity meter at 20 °C. Conductivity should not be more than 1.3 µS/cm.
5. Microorganisms: Steam condensate is tested for microbial contamination using pour plate method. There should not any microbial contamination in the steam condensate.
6. Endotoxin Test: Determine the endotoxin in the pure steam condensate and it should not be more than 0.25 EU/ml as in water for injection.
Pure steam is necessary in making drugs and other products that need to be approved by the FDA. When making sterile products, their final quality depends on how well the product sterilizes and if it is safe to use.
To be sure that pure steam systems create consistent steam that meets specifications, companies must use a lifecycle approach, complete a thorough testing program and have a clear documentation process to verify compliance and reliability.
As the industry is heavily regulated, validated pure steam systems serve a dual purpose: they meet the regulatory requirement of the FDA, while being essential components within a company’s quality and safety assurance systems.
What is Pure Steam?
Pure Steam is actually steam produced using a dedicated steam generator by using either Purified Water or Water for Injection (WFI). This means that the steam in question has been produced from the purified water and that the steam does not have any contaminants such as chemical substances, particles or microorganisms within it.Unlike regular plant steam, Pure Steam has a wide range of applications including where high levels of purity are required, such as:
- Sterilization of Equipment (SIP)
- Sterilization of tanks and pipelines
- Humidifying Clean Rooms
- Operating Autoclaves (and many other applications seen in the Pharma, Biotechnology and Medical Device industries).
Why is Validation of Pure Steam Important?
Validation of Pure Steam systems ensures that the pure steam generated is consistent in quality and executed according to established specifications of the characteristics associated with “pure” steam. Validation is important for several reasons:- Providing sterile assurance
- Preventing contamination of sterilized items
- Assuring compliance with applicable regulations
- Assuring reliable sterilization processes
Key Quality Attributes of Pure Steam
Pure steam has to conform to certain quality criteria before being declared usable for the manufacture of pharmaceuticals.1. Non-Condensable Gas (NCG)
NCGs affect the heat transfer mechanism used to sterilize equipment. High levels of NCGs can lead to:- Poor or ineffective sterilization
- Cold spots within the sterilizing unit
2. Dryness Fraction
The term "dryness fraction" is used to define the percentage of steam which is actually in a vapour state. Wet steam is capable of causing:- Inefficient or incomplete sterilization
- Water build-up within the sterilizing unit
3. Superheating
Superheated steam does not perform as effectively as saturated or wet steam when it is used for the purpose of sterilization due to its lack of moisture in comparison to saturated or wet steam; therefore, it is similar to dry air with regard to its ability to transfer heat.4. Chemical Purity
Condensate produced from pure steam should conform to specifications for the water for injection (WFI) standard and must be chemically pure.5. Microbial Quality
Pure Steam must be free of any type of contamination from microbes or from endotoxins.Components of a Pure Steam System
Pure steam systems generally consist of four components:1. Water supply (PW or WFI)
2. Steam generator
3. Piping to distribute steam
4. Collection method for condensate from the pure steam system
It is essential that all components are designed and maintained correctly in order to uphold the integrity of the overall system.
Validation Lifecycle Approach
Validation of these pure steam components will follow a similar lifecycle approach (see previous section) to that of other pharmaceutical systems.1. Design Qualification (DQ)
A DQ is an assurance that the pure steam system is designed according to the requirements of the user and will meet regulatory needs with respect to the system's design. As part of a DQ the following will occur:- Evaluation of system design
- Evaluation of materials selection
- Verification of compliance with hygienic design principles
2. Installation Qualification (IQ)
An IQ verifies that a pure steam system has been installed according to design specifications. Actions completed as part of an IQ include:- Verification of the installation of equipment
- Verification of the piping and instrumentation
- Review of the associated documentation
3. Operational Qualification (OQ)
An OQ assures that the functional capabilities of a pure steam system perform as intended under defined operating conditions. Activities to accomplish an OQ will include:- Functional testing of control systems
- Verification of alarm functions
- Verification of operating parameters
4. Performance Qualification (PQ)
A PQ is the final stage of the validation process for a pure steam system that demonstrates that the pure steam system consistently produces a pure steam product that complies with the specified quality attributes. In order to demonstrate this:- Samples will be collected from various locations within the system
- Tested for non-condensable gases, dryness and superheat
- Tested via chemical and microbiological methods
The sampling of Pure Steam
Sampling for Bacterial Endotoxin Test and chemical tests should be done separately. Depyrogenated tubes or bottles should be used for taking the sample for bacterial endotoxin test. Allow the steam to drain for minimum one minute.Open the cap of the bottle and fill the bottle with steam condensate by holding the bottle in the holder. Gloves should wear into the hands while sampling the pure steam. Tighten the cap of the bottle and mark with the sampling information. If the sample is not analyzed within 2 hours of sampling, store the sample at 2-8 °C.
Analysis of Pure Steam
Pure steam should be analyzed for following tests.1. Non-condensable Gases: Non-condensable gases are air and carbon dioxide those do not condense with the steam. These are generated due to their presence in the purified water that continuously circulates in the water distribution system. Non-condensable gases should not be more than 3.5%.
2. Steam Dryness Value: Dry steam has more energy than the wet steam. Wet steam has water with it and does not have heat energy as dry steam. Dryness of steam is determined by the latent heat. Dryness of the pure steam should not be less than 90%. High moisture content can cause the loss in energy of steam and that may cause the longer sterilization time.
3. pH: Steam condensate is analyzed for pH value at 25 ° C. It should be between 5-7.
4. Conductivity: Conductivity should be tested with calibrated conductivity meter at 20 °C. Conductivity should not be more than 1.3 µS/cm.
5. Microorganisms: Steam condensate is tested for microbial contamination using pour plate method. There should not any microbial contamination in the steam condensate.
6. Endotoxin Test: Determine the endotoxin in the pure steam condensate and it should not be more than 0.25 EU/ml as in water for injection.
Common Challenges in Pure Steam Validation
Validation generally presents many practical problems for most organizations. Common problems include:- The presence of non-condensable gases
- The insufficient dryness fraction of the steam
- Contamination resulting from a poorly designed system
- Insulation failure due to heat loss.
Role of System Design in Pure Steam Validation
A properly designed system minimizes the difficulties of performing a validation. Factors to consider when designing a system for validation are:- The use of sanitary materials such as stainless steel
- Slope to ensure proper drainage of condensate from the system
- The elimination of dead legs within the system
- Insulation of all piping
Routine Monitoring and Maintenance
Validation does not happen by accident but through constant evaluation. Routine tasks that are performed on a regular basis include:- Periodic Quality assessments of the steam being produced
- Inspection and testing of all system parts
- Maintaining all instruments by calibration
- Preventive maintenance
Documentation Requirements
Without proper documentation, no company can prove compliance with applicable regulations. The following documents are key for providing evidence of a validated and controlled system under GMP:- Guidelines and Reports (Validation protocols)
- Test Results
- Calibration records
- Maintenance logs
Regulatory Expectations
Regulatory agencies will expect that when performing inspections on pharmaceutical companies and their pure steam systems, the systems have been:- Designed and installed correctly
- Validated with all intended uses
- Regularly monitored
- Maintained in a validated state
Best Practices for Pure Steam Validation
The validation process will be successful if following a formalized structured approach. Best practices include:- Using high quality feedwater
- Designing systems to minimize the potential for contamination
- Conducting comprehensive testing
- Maintaining proper documentation
- Training personnel in system operation
Pure steam is necessary in making drugs and other products that need to be approved by the FDA. When making sterile products, their final quality depends on how well the product sterilizes and if it is safe to use.
To be sure that pure steam systems create consistent steam that meets specifications, companies must use a lifecycle approach, complete a thorough testing program and have a clear documentation process to verify compliance and reliability.
As the industry is heavily regulated, validated pure steam systems serve a dual purpose: they meet the regulatory requirement of the FDA, while being essential components within a company’s quality and safety assurance systems.
Frequently Asked Questions on Validation of Pure Steam
Q1. What is pure steam?
Answer: Pure Steam means steam generated from purified water or WFI (water for injection) for the purpose of use in the manufacture of pharmaceuticals.Q2. Why is pure steam validation important?
Answer: The importance of pure steam validation is that it ensures the quality of the steam and therefore, the effectiveness of sterilization.Q3. What are key quality attributes?
Answer: The key quality attributes of pure steam are NCG (non-condensable gas), dryness fraction, superheat and purity.Q4. What is NCG in steam?
Answer: Non-condensable gases (NCG) are found within steam and their presence affects the efficiency of the transfer of heat.Q5. What is dryness fraction?
Answer: The dryness fraction is the "dryness" of the material which is produced from the conversion of the water in the vapour state to that of the vapour (steam).Q6. How is pure steam tested?
Answer: Pure steam is verified and validated through the analysis of NCG, dryness, superheat and condensate.Q7. What is PQ in validation?
Answer: The Performance Qualification (PQ) of a validation consists of ensuring the continual operational performance of a system.Q8. What happens if steam is not pure?
Answer: If the steam is not pure, the sterilization process and the quality of the products are compromised.
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