Quality Risk Assessment

New Draft PIC/S Annex 1 – Part 4 of 8

In Part 4 of the blog series on the draft revision of Annex 1. We look at Annex 1 Chapter 7 (Utilities), which provides guidance unique to supporting process services, such as water, vacuum, steam and compressed gas systems. Almost half the clauses in this chapter relate to water systems.

Readers may also wish to view the Initial BlogPart 1, Part 2 and Part 3 of this series for context.

Chapter 7 – Utilities

Annex 1 chapter 7 on Utilities for sterile manufacture is largely brand new content (20 of the 24 clauses do not have an obvious related clause in 2007 Annex 1). Despite this, most of the requirements are consistent with current practices and are unlikely to cause major concern for most manufacturers.

Brand New Clauses in Chapter 7

Point of Contention: Clause 7.5 requires drawings to be “current” but states no explicit requirement for the drawings to be an accurate reflection of the installation. While this concern may appear pedantic, as consultants, we regularly sight drawings that contain important inaccuracies.

Secondly, it is curious that the draft requires drawings to be available for utilities, but does not explicitly require the same for processes, equipment or facilities. It is appropriate that global statement(s) be added to address this

Point of Contention: Several clauses in section 7 use the term “water system” (some refer specifically to Water For Injections (WFI), but no other grades are mentioned). While the intent appears to be that the term “water system” refers to  treatment of water for the distribution to and use directly in the process, the lack of definition could lead to confusion. For example, should a pre-treatment/feedwater plant be considered a “water system”?

Point of Contention: 7.13 states that for post-disinfection/regeneration water samples, “results should be approved before the start of use of the water system”.

For microbiological analysis, most organisations would re-commence system use at-risk, while waiting for results which may take several days. Allowance for this appears to be an oversight in the draft. However, if this action is no longer permissible, this requirement has significant impact

Point of Contention: Clause 7.15 includes the sentence “A sample from the worst case sample point, e.g. the end of the distribution loop return, should be included each time the water is used for manufacturing and manufacturing processes.”

If this statement were taken literally, some larger manufacturers would be required to take hundreds of samples each day. Tracking the need for a sample would be nearly impossible and it would likely take multiple additional staff to meet the requirement.

It is much more likely that the clause is supposed to read “… each day the water is used … “ or include another alternative word to “time” which keeps sampling requirements to a more sensible number.

Clauses with Negligible Change in Chapter 7

Clauses with Minor Change in Chapter 7

Clauses with Moderate Change in Chapter 7

The new draft Annex 1 Chapter 7 feels a little bit under-developed. In one sense, it appears to be a chapter on WFI, with some small acknowledgement of other utilities. Expectations around some critical utilities (e.g. pure steam or sterile compressed gas) are arguably insufficient, however, further expansion might lead the chapter into design guidance territory.

Its value as a stand-alone chapter will be debated. Alternative approaches (for example, as “utilities” and “process water systems” sub-sections under the Equipment chapter) should be considered.

Initial Blog

Draft Annex 1 – Part 1

Draft Annex 1 – Part 2

Draft Annex 1 – Part 3

Draft Annex 1 – Part 4 (this post)

Draft Annex 1 – Part 5

Draft Annex 1 – Part 6

Draft Annex 1 – Part 7

Draft Annex 1 – Part 8