Detailed Analysis of the PIC/S Document 'Recommendations on Qualification and Validation' - Part I

Since September 2007, the PIC/S document PI 006 has been available in Version 3 ('Recommendations on Validation Master Plan, Installation and Operational Qualification, Non-Sterile Process Validation, Cleaning Validation'). The revised Version 4 ('Recommendations on Qualification and Validation') will come into force on 1 October 2026 and significantly expands both its scope and level of detail. What is new? The following describes the changes from Version 4 compared with Version 3.

The document has increased in length from 26 pages in Version 3 to 49 pages in Version 4, and its thematic focus has become noticeably broader. New topics, or topics covered in greater detail, include quality risk management (QRM), pre-qualification stages, ongoing process verification, transport verification, packaging validation for solid dosage forms, qualification of utility systems, validation of test methods, visual inspection as part of cleaning validation, and maintaining the validated cleaning process. At the same time, content on the qualification of established (in-use) equipment and retrospective validation has been removed.

Introduction

From the outset, Version 4 consistently embeds the lifecycle concept in qualification and validation. Compared with Version 3, it introduces the expectation of a schedule covering lifecycle reviews of the state of control of qualified equipment and validated processes. More broadly, the use of statistical methods is recommended to a greater extent. The emphasis on data governance and data integrity as cross-cutting requirements throughout all qualification and validation activities is particularly clear. Change control/change management is also highlighted: changes should be closely traceable, including deadline tracking; the Quality Unit should be involved in approvals following a change; and any decision not to perform post-change effectiveness tests must be justified. QRM is intended to accompany the entire lifecycle. In this context, the document also refers to the involvement of a subject matter expert (SME). Relevant areas of risk identified by the document include, among others, adjacent activities and rooms, multi-product manufacture using equipment and premises, and supply chain risks.

Validation Master Plan

The Validation Master Plan (VMP) remains the central control document and should continue to cover qualification, requalification, prospective and concurrent validation, as well as ongoing process verification (OPV). New is the requirement for a time-defined, regular review of the VMP, with amendments made where necessary. The rationale for 'worst-case' approaches should be described. In addition, Version 4 expects, among other things, justification for requalification frequencies and a list in the VMP of the products and processes subject to ongoing process verification. The expanded requirements relating to deviation management and data integrity in the VMP are particularly important. Deviations should not only appear in protocols and reports, but should also be recorded in the formal deviation system to enable investigations. Confirmation of data integrity in qualification and validation reports should be performed by fully independent personnel.

Qualification

In the area of qualification, Version 4 expands the stage model to include pre-qualification and emphasises that different approaches are permissible. The verification approach described in ASTM E2500 is explicitly mentioned. User requirements specifications (URS), factory acceptance testing (FAT) and site acceptance testing (SAT) are either new or considerably more firmly embedded. Where formal protocols and reports are available, these activities can be integrated into the qualification process. Overall, Version 4 shifts the focus away from the former emphasis on IQ/OQ towards greater emphasis on DQ and PQ, together with a robust design specification. Deviations arising during pre-qualification or qualification should be converted into appropriate CAPA measures. Pre-qualification and qualification projects are typically initiated through a change control request, and changes to the URS should likewise be tracked through change control. The minimum requirements for IQ have been expanded. For PQ, the document recommends risk-based test rationales, increased sampling and - in a separate subsection - the use of statistical tools, such as control charts, Cpk/Ppk values and multivariate process control. Of practical relevance is the indication that 'like-for-like' component replacements may, under certain circumstances, be carried out through maintenance without being subject to change control, provided that they are documented, justified and approved by the Quality Unit. The integration of qualification aspects into the Product Quality Review (PQR) is also addressed.

In Part II of the news, you will find detailed analyses of process validation, the other qualifications and validations described in the document, and cleaning validation - together with a concluding assessment.

You can find Version 4 of the PIC/S document on the PIC/S website.