PIC/S publishes a Q&A document to assist with Annex 1

PIC/S has published a new interpretation of the revised Annex 1 in PI 058-1, "Interpretation of the Most Important Changes in the Annex 1 on the Manufacture of Sterile Products (2022)". The document was adopted by the PIC/S Committee on 16 October 2026 and entered into force on 28 October 2026. Its purpose is to support the harmonised conduct of inspections and provide a common technical interpretation of key questions that have arisen since the Annex was revised and implemented. PIC/S explicitly clarifies that PI 058-1 is not intended to introduce new GMP requirements, but to explain existing ones.

The document's origins are particularly relevant. The initial draft was prepared by Swissmedic in 2023 (I-SMI.TI.25e). It served as the starting point for the work of the joint PIC/S-EMA-WHO Working Group on the implementation of the revised Annex 1. The draft was subsequently reviewed by PIC/S members, the EMA working group and WHO. The aim is to ensure a consistent technical interpretation across PIC/S, the EU and WHO.

PIC/S explains that the draft prepared by Swissmedic in 2023 served as the basis for the joint PIC/S-EMA-WHO Working Group. The resulting document was then reviewed internationally and is intended to support a harmonised technical interpretation. It is therefore not simply an unchanged adoption of the Swissmedic Q&As. At the same time, many topics were already covered in I-SMI.TI.25e, including material transfers, WFI, PUPSIT, single-use systems, environmental monitoring and APS. PI 058-1 revisits these questions and further explains them within a harmonised framework.

One clear example of the expanded scope is the section on scope. The Swissmedic Q&As begin by asking how Annex 1 applies to ATMPs. PI 058-1 instead explicitly addresses whether a CCS may also be relevant to the manufacture of non-sterile products and further explains the structure and regular review of the CCS. Other points addressed in greater detail include the distinction between VHP bio-decontamination and sterilisation, as well as requirements for initial personnel qualification and possible disqualification.

What are the main topics covered by PI 058-1?

• Scope and general principles: CCS, material testing and risk-based interim measures for facilities that are not yet fully compliant; the objective remains to achieve full compliance with the requirements.
• Premises and equipment: Material transfers, isolator risk assessments, airflow, disinfection, and the distinction between bio-decontamination and sterilisation. VHP is not treated as a sterilisation method in all cases.
• Utilities and personnel: WFI monitoring, process gases, qualification in aseptic behaviour, and the conditions for unsupervised access to Grade A and B areas.
• Production and specific technologies: Container and single-use system integrity, sterilisation validation, PUPSIT, aseptic connections, and the design of Aseptic Process Simulations (APS).
• Environmental and process monitoring, and QC: Trend assessment and alert/action limits, Rapid Microbiological Methods (RMM) and the conditions for using them as alternatives or supplementary rapid methods, APS scope and frequency, and bioburden testing before final sterilisation.

The CCS is a central theme throughout the document. The ECA guide "How to Develop and Document a Contamination Control Strategy," can also be used as practical support when preparing a CCS. It describes a structured approach that includes mapping processes, identifying potential sources of contamination, assessing risks, and defining preventive controls and responsibilities. The guide complements PI 058-1 as a support, but does not replace regulatory requirements or a site-specific assessment. A CCS must be tailored to the product, process, facility and existing control systems.

In summary, the new PIC/S Q&A document, PI 058-1, is primarily an interpretative and harmonisation step. Manufacturers and inspectors would be well advised to focus specifically on the CCS, procedures and qualification programmes covering the topics outlined – particularly where national Q&As or internal interpretations have thus far served as guidance.