Quality Risk Assessment

New Draft PIC/S Annex 1 – Part 2 of 8

Continuing our blog series into the new draft PIC/S Annex 1 revision, (see part 1 here), part 2 looks at Chapters 3 & 4. As we move into the detailed chapters (chapter 4 and beyond), we will use categorization tables to identify and describe the significance of each change. The categories are:

  • Brand New – clauses which do not have any significant correlation to an existing clause from the 2007 version of Annex 1. Each clause is categorized for potential impact individually.
  • Negligible Change – clauses that will not, or are unlikely to, require action to ensure compliance. These may be exact or near copies of previous clauses, or they may be reworded clauses where the intent has not changed.
  • Minor Change – clauses which are likely only to affect a small number of manufacturers and require only a relatively small effort to become compliant.
  • Moderate Change – Still a relatively small number of affected manufacturers, but requiring greater effort for compliance.
  • Significant Change – Even with the significant changes, there will be some manufacturers whose practices already align with the new clauses. These changes will be significant because the number of manufacturers currently non-compliant is notably higher than for other changes, and/or the effort to address compliance is likely to be substantial compared with other changes.

Draft Annex 1 – Chapter 3 – Pharmaceutical Quality System

This chapter is entirely new. While it aligns Annex 1 with the concepts in ICH Q10, the chapter should not require any significant departure from current practices for the significant majority of organisations. A company who finds themselves non-compliant with these clauses is likely deficient against previous Annex 1 revisions too.

The concepts of PQS, QRM and investigations are described with specific connection to sterile manufacturing. For example, clause 3.2 requires assessment of impact of OOS/OOT microbiological results for both the scenario in question, but also more holistically related to historical batches. Some of the requirements in clause 3.1 can be linked back to the CCS document.

Draft Annex 1 – Chapter 4 – Personnel

With the introductory chapters out of the way, the more detailed and specific clauses start in this chapter. Chapter 4 contains 16 clauses, compared with 10 from the 2007 version. Only 4 clauses are brand new, with others previously located in different sections of Annex.

Brand New Clauses in Chapter 4

Causes with Negligible Change in Chapter 4

Point of Contention: Clause 4.8 describes requirements associated with entry to sterile facilities after engagement with high risk activities. Unfortunately, the wording offers only what is already expected when entering a sterile facility (to follow procedure). An opportunity is available to highlight that where the described high risks are involved, special additional entry activities may be required based on QRM.

Clauses with Minor Change in Chapter 4

Clauses with Moderate Changes in Chapter 4

Point of Contention: Clause 4.13 states that where clothing (presumably facility clothing) is re-used, “this should be considered as part of the qualification”. But there is no link to what qualification is being referenced. The nearest related reference to qualification is in section 4.10, but the statement in 4.13 adds nothing to the 4.10 requirement, and therefore appears redundant, or poorly described.

Clauses with Significant Change in Chapter 4

To consider: Does your gowning procedure for Grade A/B result in the coverage of all facial skin? If not, is the change required procedural, or will it require new garment components?

Despite being entirely new, Chapter 3 should not be a concern for compliant manufacturers. Chapter 4 has a high level of change when compared with the Personnel section from the 2007 Annex but, for the most part, those changes are not unexpected. The new and changed clauses are largely a reflection of improved practices that have arisen from industry interpretation of the less specific clauses from the 2007 Annex.

Initial Blog

Draft Annex 1 – Part 1 

Draft Annex 1 – Part 2 (this post)

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

Draft Annex 1 – Part 8