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High Purity Water System Validation Guidelines

As one of the most commonly used raw materials in the industry, water is not only significant in manufacturing Active Pharmaceutical Ingredient (API) but also highly monitored and scrutinized. 

Thus, water system validation in the pharmaceutical industry is an integral part of understanding the dynamic operation of pharma. Whether it is WFI water system validation or monitoring the efficacy of distribution pipes, water system validation is an important strategy to ensure controlled and consistent quality.

Importance of Water System Validation

In order to understand the importance of water system validation processes in pharma, it is first important to understand what exactly it is. It can be defined as a process of pre-determined checks and verification strategies adopted by pharma manufacturing entities to ensure that their products and processes meet the stringent water system validation guidelines set forth by international regulatory bodies such as ICH and WHO. 

A proper Water System Validation ensures:

  • The water purification system is operating in accordance with the design parameters
  • The system designed for the purification process is capable of consistently producing the desired quality of water
  •  The system designed and the water produced is free of physical, chemical, and microbial contaminants, which meet the standards of different USP monographs and maintain the same quality throughout the process of generation, storage, and distribution.

An efficient Water System Validation strategy needs to prove the efficacy of 

  •   Engineering Designs
  •   Operating Procedures
  •   Successful operating conditions during designing, installing and running
  •   Variations in periodical usage patterns

Phases of Water System Validation

The validation process for high-purity water in pharma happens in three distinct phases.

Phase 1

This is also called the investigation phase and continues for 2-4 weeks. During this period, water needs to operate constantly, and the following parameters are analyzed:

  • Sampling and testing of feed water
  • Sampling and analyzing water at every step
  • Chemical & microbial testing
  • Cleaning, sanitizing, & maintenance processes and frequencies
  • Alert and action limits
  • Production volume
  • Test-failure procedure

Phase 2

After the successful completion of Phase 1, another 2-4 weeks of validation process ensues as a part of Phase 2. The sampling process remains the same as Phase 1, and the objective here is also to determine that when the system is operated under standardized operations, the results remain consistent.

Phase 3

Phase 3 usually runs for a year, and the water can be used for manufacturing during this phase. It is a long-term analysis of the produced water and involves:

  • Reduced frequency of sampling of water after the successful completion of phases 1 and 2.
  • Accounting for seasonal variation. Seasonal trending is also done during this phase.

After the validation, a report is prepared, which is used as the primary documentation in periodic inspections, and the SOP or the Standardized Operation Procedure is determined.

Documentations Required

A standard protocol of validation requires a few documents, which include:

Verification of design document with a description of the installation processes and specifics of the functions

  •       Operating parameters
  •       Maintenance Details
  •       Training records
  •       Environmental records
  •       Plant inspection details 

Commonly Overlooked Items

Water system validation in the pharmaceutical industry is a fairly dynamic process with many big and small factors to be accounted for. It is likely that certain factors get overlooked during the process. A few of such considerations to pay attention to are:

  • UV Lights – Ultra Violet (UV) lamps are an integral process of water purification, which is used to eliminate the microorganisms during the purification process. As a standard protocol, UV lamps must be changed every six months, and the ballast providing power to the lamps should be changed every 2-3 years.
  • Feedwater – The quality and seasonal variation of feedwater play a vital role in the success of the water system validation process in pharmaceuticals.  The feedwater should be tested for pH, hardness, flow, temperature, contaminants such as iron, chlorine, & conductivity.  Operational data must be recorded and checked for emerging trends, and an alert system should be formulated to alarm the user about any inconsistencies.
  • Biofilm – Biofilm is a slimy, hydrophobic layer that often forms on the inner surface of pipelines. They house bacteria, microbes & pathogens and are firmly attached to the surface, which not only degrades the quality of the water passing through the pipes but also leads to corrosion. Since getting rid of biofilms is expensive, an efficient strategy is to prevent it to the extent possible. Chemical cleaning and sanitizing with acidic agents are the best way to curb the problem of biofilm formation.
  • Air Contamination – Non-sterile air is also a possible contaminant that may hinder the process of purification of water. It is an often overlooked factor during the validation process. Proper valve sequencing is the best way to eliminate the possibility of air contamination.
  • Microbial Limits – While the generally accepted reference for microbial content in high purity water in pharma is USP 24, it is not absolute. It depends on specific scenarios, such final dosage form. It is essential to take this variation into account and determine corrective measures. 
  • Cost of Operation – This is perhaps the most practical of all considerations, yet it is easy to overlook. A superbly complicated system may prove impossible to maintain in the long run due to the operation cost in includes. Systems, where the water is at 65 degrees to 80 degrees Celsius are considered self-sanitizing and a great way to save some cost when taken into consideration.  Also, observing preventive measures is a great way to reduce costs, as corrective measures are usually more expensive in nature.

Validations for WFI

As one of the pharma products with the most sensitive use case, WFI water system validation warrants a closer look.  The WFI water system validation process is not categorically different from other validation protocols. It entails the same principle of checking the quality of the desired product in accordance with design, installation, and operation standardizations. An efficient WFI water system validation must check for the following:

  • Chemical tests prescribed for USP monographs on WFI
  • Bacteriological purity with less than 10cfu/100ml
  • Less than 0.25EU/ml of endotoxins
  • The temperature of hot Water for Injection greater than 80° Celsius
  • Particulate matter

International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use or ICH guidelines for water system validation and WHO guidelines for purified water system validation are two of the most commonly accepted strategies worldwide for determining standard validation protocols.

While there might be variations in the specifics, all regulatory bodies worldwide agree that validation is a critical process to ensure complete safety and the best way to optimize and execute the available resources for those in the business of manufacturing pharma products.

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