/ By Panorama Consulting & Engineering Inc. / Pharmaceutical Industry • System design/ 0 Comments

Design of Purified water & WFI Systems

Water is the one of the major commodities used by the pharmaceutical industry. It is widely used as a raw material, ingredient, and solvent in the processing, formulation, and manufacture of pharmaceutical products, active pharmaceutical ingredients (APIs) and intermediates, and analytical reagents. It may present as an excipient, or used for reconstitution of products, during synthesis, during production of finished product, or as a cleaning agent for rinsing vessels, equipment and primary packing materials etc.

There are many different grades of water used for pharmaceutical purposes. Several are described in USP monographs that specify uses, acceptable methods of preparation, and quality attributes. These waters can be divided into two general types: bulk waters, which are typically produced on site where they are used; and packaged waters, which are produced, packaged, and sterilized to preserve microbial quality throughout their packaged shelf life.

There are several specialized types of packaged waters, differing in their designated applications, packaging limitations, and other quality attributes.

Different grades of water quality are required depending on the different pharmaceutical uses.

Types of Water used:

Water is the most common aqueous vehicle used in pharmaceuticals. There are several types of water are used in the preparation of drug product, such as:

  1. Non potable water: It is water that is not of drinking water quality, but which may still be used for many other purposes, depending on its quality. It is generally all raw water that is untreated, such as that from lakes, rivers, ground water, springs and ground wells.
    Purposes:

    • cleaning of outer surface of the factory
    • used in garden
    • washing vehicles etc.
  2. Potable water: It is not suitable for general pharmaceutical use because of the considerable amount of dissolved solids present. These consist chiefly of the chlorides, sulphates & bicarbonates of Na, K, Ca and Mg. A 100 ml portion of water contains not more than 100 mg of residue (0.1%) after evaporation to dryness on a steam bath.
    Purposes:

    • To use as drinking water
    • Washing & extraction of crude drugs
    • Preparation of products for external use
  3. Purified water: It is used in the preparation of all medication containing water except ampoules, injections, some official external preparations such as liniments. It must meet the requirements for ionic & organic chemical purity & must be protected from microbial contamination.
    Purposes:

    • For the Production of non-parenteral preparation/formulation
    • For the Cleaning of certain equipment used in non-parenteral product preparation
    • For Cleaning of non-parenteral product-contact components
    • For All types of tests
    • For the Preparation of some bulk chemicals
    • For the preparation of media in microbiology

Water for Injection (WFI):

Water for Injection is a solvent used in the production of parenteral and other preparations where product endotoxin content must be controlled, and in other pharmaceutical applications.(WFI) is sterile, non pyrogenic, distilled water for the preparation of products for parenteral use.

It contains no added substance and meets all the requirements of the tests for purified water. It must meet the requirements of the pyrogen test. The finished water must meet all of the chemical requirements for Purified Water as well as an additional bacterial endotoxin specification.

Since endotoxins are produced by the kinds of microorganisms that are prone to inhabit water, the equipment and procedures used by the system to purify, store, and distribute Water for Injection must be designed to minimize or prevent microbial contamination as well as remove incoming endotoxins from the starting water. Water for Injection systems must be validated to reliably and consistently produce and distribute this quality of water.

Purposes:

  • For the production of parenteral products/formulation
  • For cleaning of parenteral product-contact components

Preparation technique:

  • Distillation
  • Reverse osmosis
  • Membrane process

Storage condition:

It can be stored for periods up to a month in special tanks containing ultraviolet lamps. When this freshly prepared water is stored and sterilized in hermitically sealed containers, it will remain in good condition indefinitely.

If autoclave is not available, freshly distilled water may be sterilized by boiling the water for at least 60 minutes in a flask stoppered with a plug of purified non-absorbent cotton covered with gauze, tin-foil or stout non-absorbent paper; or the neck of the flask may be covered with cellophane and tightly fastened with cord.

WFI System validation process:

How to preform WFI system validation in Pharmaceuticals and Acceptance Criteria for Water for Injection.

Process:

  1. Perform Installation Qualification. Verify piping, fittings, proper dimensions drawings, wiring, PC software, calibration, and quality of materials.
  2. Check flow rates, low volume of water supply, excessive pressure drop, resistivity drops below set point, and temperature drop or increase beyond set level.
  3. Perform general operational controls verification testing.
  4. Operate system throughout the range of operating design specifications or range of intended use.
  5. System regulators must operate within ±2 psi of design level.
  6. Operate the system per SOP for operation and maintenance of purified water system. Perform sampling over a 1 month period per the sampling procedure and schedule.
    Test samples for conformance to current USP Water for Injection monograph, microbial content and endotoxin content. Identify all morphological distinct colony forming units (CFUs) to at least the genus level
  7. Measure the flow rate and calculate the velocity of the water, or measure the velocity directly at a point between the last use point and the storage tank.
  8. Record the range of all process or equipment parameters (set points, flow rates, timing sequences, concentrations, etc.) verified during Operational and Performance Qualification testing.

Acceptance Criteria

  1. The system is installed in accordance with design specifications, manufacturer recommendations, and cGMPs. Instruments are calibrated, identified, and entered into the calibration program.
  2. General controls and alarms operate in accordance with design specification.
  3. The system operates in accordance with design specifications throughout the operating range or range of intended use.
  4. The system flow rate must be in compliance with design specifications.
  5. All samples must meet the following criteria:
    1. Chemical Testing: Test samples must meet the acceptance criteria of the chemical tests as described in USP Monograph on Water for Injection.
    2. Bacteriological Purity: All samples must contain no more than 10 cfu/100 ml; no pseudomonas or coliform are detected.
    3. Endotoxins: All samples must contain no more than 0.25 EU/ml.
    4. Physical Properties: The temperature of the hot Water for Injection must be greater than 80°C.
    5. Particulate Matter: Small Volume Injection: The Small Volume Injection meets the requirements of the test if the average number of particles it contains is not more than 10,000 per container that are equal to or greater than 10 µm in effective spherical diameter and not more than 1000 per container equal to or greater than 25 µm in effective spherical diameter.

If you require technical assistance regarding purified water & WFI systems please feel free to contact on +91-22-66735960 or use our technical support form.

/ By Panorama Consulting & Engineering Inc. / Chemical Industry • HAZOP • International • Marketing • MEP • Pharmaceutical Industry • Safety • Thermal Mapping/ 0 Comments

Temperature Mapping for Pharmaceutical Industry

Temperature mapping is important for verifying the efficacy of temperature controlled storage systems such as cool rooms, fridges and warehouses. It is vital for businesses that work with temperature sensitive products such as pharmaceuticals or warehouses.

The process of mapping outlines the differences and changes in temperature that occur within a single temperature controlled system. This is due to influences like opening doors, proximity to cooling fans, personnel movement, and the quantity of products being stored at any given time. Temperature mapping locates the points of greatest temperature fluctuation and difference then analyses the causes of these. Conditions are created to verify that a system maintains the correct temperature in all situations when influenced by external factors such as weather and internal factors such as airflow restrictions and the operation of the Heating, Ventilation and Air Conditioning systems. The effects in difference of temperature are calculated to ensure the systems meet industry standards.

The temperature of different spaces within cooling rooms, industrial fridges and other controlled temperature environments can vary by up to 10°C. Generally, the central space within a chamber maintains constant temperature, however the corners and areas surrounding the fans will fluctuate. External seasonal weather must also be taken into account especially for warehouses.

Temperature mapping is important for businesses and organisations dealing with temperature sensitive products, like biochemical products such as medications and vaccines. Verifying that the refrigeration systems maintain an acceptable temperature level for each specific product at all times is what temperature mapping is all about, and this is supported using ongoing monitoring systems.

Once mapping has established where temperature variation points lie within the control system then monitoring can be installed. It is important to re check any back up systems to be sure that the chambers will work in other circumstances.

Different mapping equipment gives different results. It is important to ensure that the equipment being used has sufficient accuracy ratings to give reliable data. For example, better equipment will provide readings that are accurate within plus or minus 0.3°C, whereas budget equipment may only have accuracy ratings of within 2.0°C. For products that must be stored within a limited temperature range, this budget equipment cannot provide sufficiently specific temperature data.

Warehouses must have information regarding the building’s external conditions, as it is vital for effective mapping and monitoring. Warehouses are generally mapped for a full year to ensure all external conditions are accounted for in the data. This also helps to determine placement of monitoring systems due to influence of external conditions.

Temperature-controlled rooms such as fridges or cold rooms can be mapped once as their external environment is controlled. However, it is advisable to make sure that other external forces that could change their temperatures significantly do not heavily influence the HVAC systems of these buildings or environments. The mapping in warehouses should take into account the fluctuation in the warehouse temperatures and conduct the tests during its most extreme levels.

Load testing is important aspect of the temperature mapping process. It investigates how expected product levels interact with individual temperature controlled chambers. This testing takes into account whether the product will arrive in the required condition or if cooling is necessary. Testing should verify whether the chamber could cope with the maximum specified load arriving all at once to then be cooled. If it can operate properly in this situation, as well as operating effectively at full capacity, the chamber can be considered sufficiently load tested. It is also advisable to test the system’s performance by simulating failures, to ascertain whether the system could be used even while experiencing some equipment failures.

Once the mapping process has been completed, sensors should be installed to allow for continued surveillance of the areas that have been identified as being most influenced by temperature change. The stable areas should be monitored to help with any troubleshooting.

Monitoring systems should be planned and documented according to the scientific rationales shown by the temperature mapping procedure. This development strategy should then be reviewed and approved by the system owners as well as by an independent quality unit before being installed. Sensors should be placed around the products, around major potential temperature influences such as doors and cooling fans, and at different heights, especially in larger chambers.

Sensor equipment can be split into zones according to the area affected by similar influences. For example, in a square or rectangular chamber, the zones in corners away from doors will behave much the same as each other, as will the zones adjacent to doors or fans. If the monitoring devices are zoned, data can be compared to provide overall information on how the system usually functions.

To summarize, temperature mapping provides information on warmer and colder areas within temperature-controlled environments. They supply details on the overall operation of the systems. After temperature mapping a system, monitoring equipment can be installed to provide real-time feedback on system operations and its stability for product protection.