PIC/S PI 058-1 in force: Q&A interpretation of the 2022 Annex 1 changes on sterile products

In short: PIC/S has published PI 058-1, a 29-page question-and-answer document that explains how inspectors should read the most important changes in the 2022 Annex 1 on sterile products. The document states that it adds no new GMP requirements. It entered into force on 28 October 2026.

What changed

PI 058-1 replaces the earlier interpretation document PI 032-2 (January 2010), which belonged to the old Annex 1. According to the document, the PIC/S Committee adopted it on 16 October 2026 and it entered into force on 28 October 2026. It was prepared by the PIC/S–EMA–WHO joint implementation working group on Annex 1, starting from a draft by Swissmedic, and the stated aim is that PIC/S, the EU and WHO read Annex 1 the same way.

Section 2.1.2 of the document says its purpose “is not to introduce any new GMP requirements”. The text is organised as questions and answers that follow the Annex 1 sections: scope, principle, pharmaceutical quality system, premises, equipment, utilities, personnel, production and specific technologies, environmental and process monitoring, and quality control.

Examples of what the answers cover:

• Airflow in cleanrooms: Annex 1 paragraph 4.30 gives 0.36–0.54 m/s as a guidance value for unidirectional airflow. The Q&A says a different air speed may be used if it is scientifically justified in the contamination control strategy (CCS).
• Sterilising filters: PUPSIT (pre-use post-sterilisation integrity testing) is required, whenever feasible, for filters used for final product sterilisation. For other sterilising-grade filters, such as those controlling bioburden upstream, the document says integrity testing should be risk-based and consistent with the CCS.
• Bioburden: the document says bioburden should be tested on each batch, for both aseptically filled and terminally sterilised products, immediately before the final sterilising filter or the terminal sterilisation step.

Who it affects

Manufacturers of sterile products (injectables, ophthalmics and similar) that are inspected by PIC/S member authorities, or that supply markets where Annex 1 is the reference, and the QA, validation and microbiology staff who write the CCS. How an Indian inspectorate uses the document is a matter for that inspectorate; the document itself is addressed to inspectors and industry in PIC/S countries.

Key dates

• 25 August 2023: revised Annex 1 enters into force (paragraph 8.123 binding from 25 August 2024), as recalled in the document.
• 16 October 2026: adoption by the PIC/S Committee.
• 28 October 2026: PI 058-1 enters into force.

What to do now

• Read the Q&A sections that match your products and processes, especially the ones on CCS, cleanroom airflow, filtration and bioburden.
• Compare your CCS and filter integrity-testing procedures with the answers. This is an example in-house approach, not a regulatory requirement: list each answer that touches your site in a short gap table, with an owner and a date.
• Replace references to PI 032-2 in SOPs and audit checklists.
• Train the people who write or review media fill, filter validation and environmental monitoring documents on the points that apply to them.

Related reading: Production of sterile pharmaceutical products and SOP for testing container closure integrity by microbial ingression.

Official source

• PI 058-1 Recommendation: Interpretation of the most important changes in the Annex 1 on the manufacture of sterile products (2022) — PIC/S, 2026-10-28. Link