Quality Risk Assessment

PIC/S – New Draft Annex 1 – Part 3 of 8

In Part 3 of the blog series on the draft revision of Annex 1, we look at chapters 5 and 6, on the subjects of Premises and Equipment respectively.

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

Draft Annex 1 – Chapter 5 – Premises

The new Premises chapter is significantly expanded. It contains 34 clauses, compared with 10 in the 2007 version. 10 clauses are brand new, meaning a significant number (14) have been relocated from other sections in the previous version.

Point of Contention: Clause 5.14 is written almost as design guideline rather than a regulatory requirement. If it is suggested practice, it is arguable that Annex 1 is not the appropriate place for it. If it is intended as an enforceable GMP, it raises several questions: is the clause adequately described? What are the consequences for legacy facilities? Which areas require observation without entry – all clean areas, or just A/B or some subset of areas? Is it the practice of observation without entry or just the ability to do so?

Clauses with Negligible Change in Chapter 5

Point of Contention: Clause 5.34 singles out vapourised hydrogen peroxide (VHP) as a useful fumigant. While VHP is currently the most widely used method of vapour disinfection, it is hard to understand why it has been singled out, when several other methods have been shown to be comparably effective (e.g. NO2, Cl2, O3 and ionized hydrogen peroxide, which is distinct from VHP). The singling out of VHP is unnecessary and risks creating industry bias toward that technology. In time, it may also appear outdated if other technologies surpass VHP.

Clauses with Minor Change in Chapter 5

Clauses with Moderate Change in Chapter 5

Point to Consider
: Do you currently justify execution (or absence) of air flow visualization studies in non uni-directional flow zones on QRM principles?

Clauses with Significant Change in Chapter 5

Point of Contention
: Clause 5.3 states that “only grade C cleanrooms should interface with the grade B aseptic processing area”. This could be interpreted as:1) rooms with a direct air passage to Grade B, where material or personnel may enter Grade B (e.g. via a door) shall be Grade C; or 2) rooms from which Grade B is accessed in any way (including, for example, via an actively ventilated pass-through) shall be Grade C). If interpretation 2 is correct, it may result in significant physical and/or operational modifications for some facilities. Not only where Grade B and Grade D may interface via an adtive pass-through, but also where Grade A or B areas interface with Grade D or lower classified areas in an”exit only” manner (e.g. where a high pressure differential through a wall opening and a conveyor system allows the transfer of fully integral containers for inspection and/or labelling operations)

Draft Annex 1 – Chapter 6 – Equipment

The new Equipment chapter features 10 clauses, up from 5 in the 2007 version. There are 5 brand new clauses. This section is arguably the least impactful new section with few clauses of notable impact.

Brand New Clauses in Chapter 6

Clauses with Negligible Change in Chapter 6

Clauses with Minor Change in Chapter 6

The new draft Annex 1 Chapter 5 brings some long-awaited clarity around certain issues for premises, and spells out some requirements that have only been implicit historically.

The new draft Annex 1 Chapter 6 poses minimal change or cause for concern, but in both chapters, there is still room for improvement when it comes to limiting interpretation.

Initial Blog

Draft Annex 1 – Part 1

Draft Annex 1 – Part 2

Draft Annex 1 – Part 3 (this post)

Draft Annex 1 – Part 4

Draft Annex 1 – Part 5

Draft Annex 1 – Part 6

Draft Annex 1 – Part 7

Draft Annex 1 – Part 8