Purified water (PW) is used in the pharmaceutical industry as a raw material in production or to clean equipment. It is, therefore,
important that the water meets the set standards and constantly provides the specified quality and quantity to ensure there
is no contamination of the product or equipment. Depending on quality, raw water can be difficult to purify, and can require
various processing stages to obtain PW quality. Raw water quality can also change with the seasons so conducting regular inspections,
tests and samples is imperative to ensure that the installation complies with regulations and the user's requirements on a
continuing basis.
Requirements for PW installations
A PW installation must meet the following requirements regarding water quality:
- Pharmacopoeias (e.g., US Pharmacopeia,1 European Pharmacopoeia,2 or Japanese Pharmacopeia3 ).
- cGMP, 21 Code of Federal Regulations.4
- National laws and regulations.
There are also other requirements that do not stem from the product quality, but concern operator safety, including European
directives 98/37/EC (Machinery);5 89/336/EC (Electromagnetic compatibility);6 73/23/EC (Low voltage);7 PED 97/23/EC (Pressure equipment);8 Underwriters Laboratories (UL) standards9 and American Society of Mechanical Engineers (ASME) codes and standards.10,11User requirement specification
The prospective owner of the system creates a user requirement specification (URS). From a practical perspective, and to obtain
good traceability, it is important that requirements are clear, well-structured, numbered and testable. A requirement such
as 'heat exchangers must be of a high quality' becomes difficult to handle in validation because it is not a tangible statement.
The requirements must also be at the right level regarding acceptance criteria (e.g., what temperature or hardness has to
be reached or what materials are required?). It is also essential to avoid setting requirements unnecessarily high during
start-up, testing or operation that, on closer inspection, do not need to be met. In fast-track projects where time is an
important factor, changes and updates take time and it is preferable to assess the installation carefully at the start in
the requirements specification. A risk analysis regarding the end product (e.g., water quality) should be performed before
compiling the URS. The requirements relating to the safety of plant operators must be part of the risk analysis that occurs
for CE marking of the installation, according to the machinery directive.
It is an advantage to divide the requirement specification into 'C' and 'Q' requirements with the help of the risk analysis
performed. This is described in the ISPE Baseline Guide Volume 5, Commissioning & Qualification.12 C stands for commissioning and the requirement will then be tested under a factory acceptance test (FAT) or a site acceptance
test (SAT). Q stands for qualification and the requirement is tested under an installation qualification (IQ) or an operation
qualification (OQ). To find and select the typical Q requirements for the system, the ISPE's Baseline Guide Volume 4, Water & Steam Systems13 and FDA's Guide to Inspection of High-Purity Water Systems14 can provide assistance.
The easiest way to create traceability in the project is to write the requirement specification in table format, with the
requirements divided into C and Q requirements, which can then be given to the supplier as a Word document for further processing
and completion of the references to design documents and tests. The supplier can then create a traceability matrix from the
file, or copy the requirements to an Excel table. This avoids having to write the requirements in the matrix again, thus eliminating
a possible source of errors and saving time.
