Quality Risk Assessment

PIC/S – New Draft Annex 1 – Part 7 of 8

This chapter contains information which was previously covered under the headings “Clean Room and Clean Air Device Monitoring”, and also clauses 66-69 on Aseptic Process Simulation (APS) which was under the old heading “Processing”. In addition to the 21 clauses from 2007 that have been revised and reallocated to 22 new clauses, there are 27 new requirements that have previously not been stated explicitly. Readers may also wish to view the Initial BlogPart 1Part 2Part 3Part 4, Part 5 and Part 6 of this series for context.

There is some logic in presenting APS alongside the environmental monitoring (EM) requirements in this new chapter, however, the terminology used should be questioned, as per the point of contention below:

Point of Contention: Chapter 9 uses the term “non-viable” when referring to airborne particulate monitoring. Presumably this term was chosen to highlight the contrast and difference between particulate monitoring and viable microbiological monitoring, but this is arguably insufficient reason to use a term which is imprecise at best and erroneous at worst.

Standard light scattering airborne particle counters (LSAPC) are incapable of distinguishing between viable and non-viable particles and, therefore, will include viable particles in any total count provided. The contention may seem semantic, given that the percentage of viable particles in an LSAPC sample will likely be extremely low, but equally there seems no reasonable justification for the inaccuracy given that accurate common use terms (airborne particle monitoring or total particle monitoring) already exist.

To minimise confusion, from this point forward this blog uses the term “non-viable” when describing total airborne particles in accordance with the draft revision.

Brand New Clauses in Chapter 9

Point of Contention: Clause 9.46 provides clear and unambiguous instruction for managing production and release post APS event. However, it appears that this clause only considered those manufacturers whose products can tolerate the hold-release period required to obtain microbiological results of the APS.

Several sterile products cannot be held for such lengths of time (e.g. some pharmacy compounding or radiopharmaceuticals) due to patient requirements or product degradation. Those manufacturers would either need to stop manufacturing while awaiting APS results (usually not a viable option) or will be non-compliant with the requirement as written.

Clauses with Negligible Change in Chapter 9

Point of Contention: Clause 9.27 appears to be providing information on non-viable monitoring requirements, but is located in the viable monitoring section. This leads to 2 possibilities:

a) This clause was intended for the non-viable section, but the mis-location was not identified in editing. If so, this clause should be compared with the updated clauses 9.14, 9.15 and 9.16. 9.27 appears redundant when making the comparison.

b) This clause was intended to establish “continuous” monitoring requirements for viable monitoring, but the clause was not appropriately updated to consider viable monitoring limitations. This seems less likely than a), but either way, the clause needs to be revisited and removed or significantly modified.

Clauses with Minor Change in Chapter 9

Clauses with Moderate Change in Chapter 9

Clauses with Significant Change in Chapter 9

Like many of the chapters before it, chapter 9 is a mixture of improved clarity, explicit confirmation of expectations which have previously been implied, and the occasional hiccup in expression which may cause added confusion.

The separation of the EM and APS topics in a single chapter is probably more logical, but it is also clear that there remains some challenges, particularly for manufacturers of products that are not produced by “traditional” sterile manufacturing techniques.

Initial Blog

Draft Annex 1 – Part 1

Draft Annex 1 – Part 2

Draft Annex 1 – Part 3

Draft Annex 1 – Part 4

Draft Annex 1 – Part 5

Draft Annex 1 – Part 6

Draft Annex 1 – Part 7 (this post)

Draft Annex 1 – Part 8