Water has one of the highest levels of raw material consumption in pharmacy. It is used for formulation preparation, cleaning equipment, laboratory testing and many other production purposes. Due to its widespread use, microbiological quality is critical in assuring the safety of all products from pharmacy and meeting regulatory standards.
Purified water systems are designed to produce water that meets all required specifications according to pharmacopeial standards (i.e., standards created by the United States, European and World Health Organization).
One of the major problems faced in maintaining purified water systems is biocontamination – or the presence and growth of living organisms (such as bacteria or fungi) and bio-films in the water system.
Therefore, controlling biocontamination effectively is an essential part of maintaining water quality and adhering to Good Manufacturing Practices (GMP).
Purified water systems generally consist of five individual components of water treatment:
1) Pre-treatment, including filtering and softening
2) Reverse osmosis (RO)
3) Deionization
4) Ultraviolet light (UV) disinfection
5) Reactively-used water distribution systems
After all contaminated/bio-volatilized water has gone through these treatment systems, it is then routed through the delivery loop to locations of final use for product creation.
Since water sources are known to support microbial development, all aspects of these purified water systems need to be designed to limit contamination, and consistently/maintain the purifying equipment so as to eliminate the chance of contamination occurring again.
Microbes generally will migrate from the entire contents of the water system and generate a microbial community called biofilm, with it attaching itself to various surface areas within a water systems' piping or holding tanks. Once biofilms are formed on surfaces within a water system(s) or building, they are extremely difficult to get rid of, as they generally are continuously releasing contaminants from their surfaces into the water supply.
Biocontamination can directly result in:
1) Product contamination
2) Batch rejections
3) Regulatory non-compliance
4) Patient safety hazards
Therefore, monitoring and control are essential.
RO Systems use semi-permeable membranes to remove:
3. Ultraviolet (UV) Disinfection
Ultraviolet disinfection systems are often used to control microbial growth in purified water systems.
The use of 254 nm UV light damages microbial DNA, preventing microbes from reproducing.
Benefits of using UV disinfection include:
Thermal sanitation will improve the following:
Examples of common sanitizing agents are:
One of the methods of microbiological testing will be through the following:
Routine testing will ensure that the water distribution system remains in compliance with microbiological limits.
- Establish and maintain high flow velocity in pipes
- Hygiene/sanitation of the water system through routine sanitization cycles
- Avoid stagnant water in the water system
- Use sanitary pipe materials for system
Biofilm development may require aggressive cleaning/sanitizing.
A validated system goes through three phases of validation:
Phase 1 – System Assessment
Investigation of the system performance and development of operational parameters.
Phase 2 – Operational Validation
Demonstration of consistent water quality under normal operating conditions.
Phase 3 – Long Term Monitoring
Confirmation of sustainable performance of the water system over time.
A validated system consistently provides water meeting pharmacopeial specifications.
To maintain GMP, and in accordance with the requirements of the FDA and other regulatory agencies, pharmaceutical companies must adhere to strict criteria with regard to their water systems.
The basic expectations associated with GMP include:
Purified water systems used in the manufacture of pharmaceuticals are highly susceptible to contamination by microorganisms and thus are identified as critical risk factors for quality assurance. Microbial contamination of products may result in a loss of product quality and regulatory compliance, as well as may adversely affect patient safety.
Effective methods for controlling biocontamination include good water system design, the use of various water filtration technologies, ultraviolet (UV) disinfection, thermal and chemical sanitization of water systems, and continuous monitoring for microbial contamination.
By implementing the above methods and strictly adhering to GMP requirements, pharmaceutical manufacturers can guarantee that their purified water systems are consistently providing drug manufacturers with products that comply with the compendia standards for water and that these purified water systems support the manufacture of drugs in a safe manner.
One of the major problems faced in maintaining purified water systems is biocontamination – or the presence and growth of living organisms (such as bacteria or fungi) and bio-films in the water system.
Therefore, controlling biocontamination effectively is an essential part of maintaining water quality and adhering to Good Manufacturing Practices (GMP).
Understanding Purified Water Systems
A purified water system is an engineered system to filter out impurities, foreign particles, and biological organisms from incoming water sources to be used in either the production of products or as a source of water for manufacturing processes to meet the expectations of being a pharmaceutical-compatible product.Purified water systems generally consist of five individual components of water treatment:
1) Pre-treatment, including filtering and softening
2) Reverse osmosis (RO)
3) Deionization
4) Ultraviolet light (UV) disinfection
5) Reactively-used water distribution systems
After all contaminated/bio-volatilized water has gone through these treatment systems, it is then routed through the delivery loop to locations of final use for product creation.
Since water sources are known to support microbial development, all aspects of these purified water systems need to be designed to limit contamination, and consistently/maintain the purifying equipment so as to eliminate the chance of contamination occurring again.
What is Biocontamination in a Purified Water System?
Microbial growth in water systems is referred to as "biocontamination." The organisms that cause biocontamination can include all forms of bacteria such as Pseudomonas aeruginosa, E. coli, and Burkholderia cepacia, among others.Microbes generally will migrate from the entire contents of the water system and generate a microbial community called biofilm, with it attaching itself to various surface areas within a water systems' piping or holding tanks. Once biofilms are formed on surfaces within a water system(s) or building, they are extremely difficult to get rid of, as they generally are continuously releasing contaminants from their surfaces into the water supply.
Biocontamination can directly result in:
1) Product contamination
2) Batch rejections
3) Regulatory non-compliance
4) Patient safety hazards
Therefore, monitoring and control are essential.
Sources of Biocontamination
Contamination sources are a key factor when trying to prevent microbials form developing in your purified water systems.1. Raw Water Source
Municipalities typically supply raw water with cities and towns containing microorganisms in their municipal water supply an inlet to the purification system.2. Poor Design of Systems
Dead legs, stagnant areas, and slopes that are not designed correctly in your pipes cause favorable conditions for microbials to survive by providing them with a safe environment to grow and multiply in.3. Inadequate Sanitation
Regular sanitation procedures, if not followed regularly, allow for microbials to colonize and establish themselves in either tank or pipe.4. Biofilm Development
If microbials are allowed to attach themselves to a surface, they can form a thick layer of biofilm over themselves which protects them from most disinfecting agents.5. Human Contact
Microbial contamination can also occur from improper handling or maintenance of the system by employees.Key Biocontamination Control Techniques
Successful control of biocontamination requires an integrated approach – using system design; monitoring; and sanitisation as a combination.1. System Design
A well-designed purified water system will minimize the opportunity for microbial growth. This includes:- Continuous circulation loops to prevent stagnant water.
- A smooth stainless steel piped distribution system that prevents microbial attachment.
- Very few dead legs in a distribution system.
- A proper slope for drainage.
- Use sanitary valves and fittings.
2. Reverse Osmosis and Filtration
Reverse osmosis (RO) has been proven to be one of the best methods to remove microorganisms and dissolved impurities from water.RO Systems use semi-permeable membranes to remove:
- Bacteria
- Viruses
- Dissolved salts
- Organic matter
3. Ultraviolet (UV) Disinfection
Ultraviolet disinfection systems are often used to control microbial growth in purified water systems.
The use of 254 nm UV light damages microbial DNA, preventing microbes from reproducing.
Benefits of using UV disinfection include:
- Non-chemical disinfection method
- Continuous control of microorganisms
- No negative effect on water chemistry
4. Thermal Sanitation
Hot water sanitation is an excellent way to minimize microbial pollution. The method consists of moving hot water through the distribution system (70-80 degrees Celsius) to kill the microorganisms.Thermal sanitation will improve the following:
- Killing bacterial and biofilms off
- Lowering the level of microbial load
- Helping to achieve the long-term hygiene of a system
5. Chemical Sanitation
Chemical disinfectants can also be used on a periodic basis to clean the water distribution systems.Examples of common sanitizing agents are:
- Ozone
- Hydrogen Peroxide
- Peracetic Acid
- Chlorine Based Disinfectants
6. Routine Microbiological Monitoring
Continuous monitoring allows for the detection of microbial contamination at an early stage.One of the methods of microbiological testing will be through the following:
- Total Microbial Counts
- Endotoxin Testing
- Detection of Biofilms
- Collecting samples from various points of use
Routine testing will ensure that the water distribution system remains in compliance with microbiological limits.
7. Preventing Biofilm from Forming
Strategies used to control biofilm formation are as follows:- Establish and maintain high flow velocity in pipes
- Hygiene/sanitation of the water system through routine sanitization cycles
- Avoid stagnant water in the water system
- Use sanitary pipe materials for system
Biofilm development may require aggressive cleaning/sanitizing.
8. Validating Water Systems
Prior to routine use, the validated water system must be verified before beginning routine use.A validated system goes through three phases of validation:
Phase 1 – System Assessment
Investigation of the system performance and development of operational parameters.
Phase 2 – Operational Validation
Demonstration of consistent water quality under normal operating conditions.
Phase 3 – Long Term Monitoring
Confirmation of sustainable performance of the water system over time.
A validated system consistently provides water meeting pharmacopeial specifications.
Importance of GMP Compliance
Ensuring water purity and its system's performance is simply stated as a requirement of GMP.To maintain GMP, and in accordance with the requirements of the FDA and other regulatory agencies, pharmaceutical companies must adhere to strict criteria with regard to their water systems.
The basic expectations associated with GMP include:
- Written maintenance procedures
- Routine water monitoring programs
- Calibration of instrumentation
- Personnel training and competency
Purified water systems used in the manufacture of pharmaceuticals are highly susceptible to contamination by microorganisms and thus are identified as critical risk factors for quality assurance. Microbial contamination of products may result in a loss of product quality and regulatory compliance, as well as may adversely affect patient safety.
Effective methods for controlling biocontamination include good water system design, the use of various water filtration technologies, ultraviolet (UV) disinfection, thermal and chemical sanitization of water systems, and continuous monitoring for microbial contamination.
By implementing the above methods and strictly adhering to GMP requirements, pharmaceutical manufacturers can guarantee that their purified water systems are consistently providing drug manufacturers with products that comply with the compendia standards for water and that these purified water systems support the manufacture of drugs in a safe manner.
No comments:
Post a Comment
Please don't spam. Comments having links would not be published.