Regulatory norms for pharmaceutical water systems

Kishor Datar

From the earlier chapters we know that,

• water contains contaminants.
• Contaminants depends on source of water
• Level of contamination also depends on physical properties of water like pH, temperature etc.
• It is an important compound used by all industries as well as is important for life.

With above synopsis it is clear that if the water is to be used in industry or for drinking purposes, there has to be some guideline for control over the contaminants.

Moreover in pharmaceutical manufacturing units, water is used as,

• Raw material
• Cleaning agent

Is it OK to accept available water specially when used as raw material or cleaning agent in the pharma industry?

Let us take few examples,

Example 1:
Source water available is used to prepare a batch of liquid injectables. The source water is available from nearest river/ dam.

Consequences:
As we learned, surface water will have a high degree of bacterial / organic contamination. Since the injectable is administered via blood and is used when the human is ill, if this water is used, along with the medicine, contaminants in water will also get injected into the human body.

Example 2:
For the cleaning of above manufacturing tank, source water is used available from bore well.

Consequences:
As we learned, bore well water will have a high degree of contamination with dissolved solids. Higher contamination of dissolved solids may result in residue left behind on surface of manufacturing tank and the same will get dissolved when the next batch is manufactured.

These contaminants will become a part of the solution prepared and some of the contaminants can pose a risk to patients.

The above examples make it clear that, it is essential to have some guidelines for the quality or parameters of water to be used for various purposes in the pharma industry.

To overcome this issue, almost all regulatory agencies have addressed this issue in the form of types of water and respective quality attributes.

USFDA defines 8 grades of water:

1. Non-potable
2. Potable (drinkable) water
3. USP purified water
4. USP water for injection (WFI)
   There are no monographs in the USP on potable water and non-potable water.
5. USP sterile water for injection
6. USP sterile water for inhalation
7. USP bacteriostatic water for injection
8. USP sterile water for irrigation

The last four types of water are “finished” products that are packaged and labeled as such. Hence they are considered as “Finished Products” and not as Raw Material/ Cleaning Agents.

The USP purified water and the USP WFI are components or “Raw / Ingredient materials” as they are termed by the USP, intended to be used in the production of drug products.

In the pharma industry, “Clean Steam” is also used in injectable facilities and same is not referred by any regulatory agencies.

However, cGMP for LVP (1976) indicates that “feed water for boilers supplying steam that contacts components, drug products and drug product contact surfaces shall not contain volatile additives such as amines or hydrazine”.

Normally to produce “Clean Steam”, Purified Water is used as feed water and converted to steam in a special boiler.

EU specifies following types of water,

• Purified water
• Highly purified Wwater
• Water for injection

Further to this EU specifies the water quality required based on the intended use of water.

Reference to US FDA / EU guidelines it is clear that regulatory agencies have specified the type of water and quality of type of water to be used in pharma manufacturing.

Parameters furnished by regulatory agencies for these types of water is in the accompanying tables.

Conductivity PUW/WFI- 1.2µS/cm at 25° C

From the last two articles and this article it is clear that being a universal solvent and also a sustainer of life, source water, irrespective of the source, will carry some contaminants with it.

These contaminants will vary with the sources of water/ geological location, personal hygiene being followed etc.

However it is clear that irrespective of above fact, the regulatory guidelines expect to have consistency of water quality when used as a raw material or as a cleaning agent in a pharma manufacturing unit.

Thus it is evident that with respect to regulatory and safety aspects source water requires to be treated before it can be used in pharma manufacturing units.

We will see major such treatments being used, few since many decades, few in past few years, in next few articles to come, hence keep reading these articles regularly.

(The author can be contact at [email protected])