Quality Risk Assessment

PIC/S – New Draft Annex 1 – Part 6 of 8

As noted in Part 5 of the blog series on the draft revision of Annex 1, Parts 5 & 6 look at Chapter 8 (Production & Specific Technologies).
Part 5 focussed on terminal sterilisation of products and related sterilising processes. “PIC/S – New Draft Annex 1 – Part 6 of 8” looks at the remainder of Chapter 8, and discusses aseptic processing, finishing of products and specific production technologies.
Readers may also wish to view the Initial BlogPart 1Part 2Part 3Part 4 and Part 5 of this series for context.

Chapter 8, Part B – Aseptic Processing, Finishing Sterile Products and Specific Technologies (Clauses 6-29 & 78-123)

In this second look at Chapter 8, we explore not only 4 topics carried over from the 2007 version, but also all 4 new production related topics. Part 6 covers mostly information new to the Annex – of the 70 clauses looked at this this part, 46 are brand new (including 22 from the new sections).

The sub-headings from the draft revision covered in Part 6 are:

  • Aseptic processing (clauses 6-16)
  • Finishing of sterile products (17-29)
  • Filtration of medicinal products which cannot be sterilized in their final container (78-89)
  • Form-Fill-Seal (90-92)
  • Blow-Fill-Seal (93-104)
  • Lyophilisation (105-111)
  • Closed systems (112-116)
  • Single use systems (117-123)

Brand New Clauses in Chapter 8

Clauses with Negligible Change in Chapter 8

Clauses with Minor Change in Chapter 8

Point of Contention: Clause 8.84 relates to the highly debated topic of mandatory Pre-Use, Post-Sterilisation Integrity Testing (PUPSIT). In recent years, there has been a strong regulatory push to mandate the requirement in Europe (but not in the USA). There has been similarly strong resistance from both manufacturers and filter vendors, who see PUPSIT primarily as a business risk decision, not a quality enhancement.

The draft revision makes it clear that the authors see the requirement as mandatory, however, the justification provided for PUPSIT:

“ … in case of damage and loss of integrity caused by processing …”

is both confusing and highly questionable. The precise purpose of the post-use test is to assess the filter for damage and loss of integrity caused by processing, and therefore, if this were the true purpose of PUPSIT, then PUPSIT would be redundant. The purpose (and validity) of PUPSIT has been long debated, but the inclusion of this justification is unhelpful at best.

Clauses with Moderate Change in Chapter 8

Clauses with Significant Change in Chapter 8

That concludes the 2-part focus on Chapter 8. The chapter is very broad and could possibly benefit from further sub-division, however, it is understood that this is difficult given the intent for (and benefits of) alignment with Part I of the GMP code.

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  (this post)

Draft Annex 1 – Part 7

Draft Annex 1 – Part 8