A Product Quality Review is a periodic, documented evaluation of everything that happened to a product over a defined period, carried out to answer three questions: is the process still consistent, are the specifications still appropriate, and what should change. That is the whole purpose, and it is stated almost word for word in EU GMP Chapter 1, paragraph 1.10. Everything else in the paragraph, the list of twelve content areas, is the evidence the review must consider in order to answer those questions honestly.
Most PQRs that generate findings do not fail because a content area is missing. They fail because the author treated the list as the deliverable. Twelve sections were filled with data, a standard sentence was placed at the end, and nobody asked the three questions. This guide is about the questions.
What the regulations say
EU GMP Chapter 1, paragraph 1.10, requires 'regular periodic or rolling quality reviews of all authorised medicinal products, including export only products', conducted 'with the objective of verifying the consistency of the existing process, the appropriateness of current specifications for both starting materials and finished product, to highlight any trends and to identify product and process improvements'. The reviews 'should normally be conducted and documented annually, taking into account previous reviews'. Then comes the list of twelve items, (i) to (xii), that the review 'should include at least'. PIC/S PE 009 Chapter 1 carries the same paragraph, so the requirement is identical across PIC/S member inspectorates.
Paragraph 1.11 is the half that gets forgotten. It requires the manufacturer 'and, where different, marketing authorisation holder' to evaluate the results and decide whether corrective and preventive action or revalidation is needed, under the pharmaceutical quality system. It requires management procedures for the ongoing management of those actions, verified during self-inspection. It permits grouping by product type where scientifically justified. It requires a technical agreement between the MAH and the manufacturer defining who does what. And it makes the Qualified Person responsible for batch certification, together with the MAH, responsible for ensuring the review is 'performed in a timely manner and is accurate'.
Paragraph 1.10 does not stand alone. EU GMP Annex 15, section 5.28 onwards, requires manufacturers to monitor product quality under ongoing process verification 'to ensure that a state of control is maintained throughout the product lifecycle with the relevant process trends evaluated', with the extent and frequency of that verification reviewed periodically and statistical tools used, where appropriate, to support conclusions about variability and capability. Annex 15 expects ongoing process verification to feed the product quality review, and inspectors read the two together: a PQR that only tabulates results will be judged against the Annex 15 expectation of statistical evaluation. Annex 16 closes the loop from the other side, because the certifying QP must be able to rely on the pharmaceutical quality system, and the PQR is one of the records that system produces.
For active substances, ICH Q7 section 2.5 (paragraphs 2.50 and 2.51) requires regular quality reviews 'with the objective of verifying the consistency of the process', with a seven-item content list that is a subset of the EU one, and a requirement that the results be evaluated, that corrective action or revalidation be considered, and that agreed actions be completed 'in a timely and effective manner'. ICH Q7 is adopted in the EU as Part II of EudraLex Volume 4, so for an active substance manufacturer the Q7 list is the regulatory requirement, and an EU-format review built to 1.10 covers it.
The three questions, in the order an inspector asks them
- Is the process consistent? Not 'were all batches within specification' but 'is the process producing the same result batch after batch, with a spread that the specification comfortably contains, and without drift'. This is answered by trending, not by a table.
- Are the specifications appropriate? For starting materials and for the finished product. A specification can be too loose (the process routinely produces results at 98 to 102 and the limit is 90 to 110) or too tight (the process is capable but the in-process limit generates constant deviations). Both are findings if nobody has noticed.
- What should change? Improvements to product and process. If the review identifies nothing to change for a product with nine deviations and a stability result that is drifting, the review has not been done.
What the PQR is not
It is not a repeat of batch release. Every batch in the review has already been assessed, tested and certified. The PQR does not re-release them. It looks across them for what release cannot see: a slow drift in a result, a failure mode that recurs every quarter, a supplier whose material is always at the edge of specification, a change made in March whose effect is visible from May.
It is not a metrics dashboard. Counts of deviations, complaints and changes are inputs. A count is not an evaluation. 'Fourteen deviations were raised' tells the reader nothing until it is followed by what they were about, whether they repeat, and whether last year's actions reduced them.
It is not a compliance artefact produced for the inspection. Paragraph 1.11 makes it an input to the pharmaceutical quality system, and ICH Q10 section 3.2.4 lists periodic quality reviews among the inputs to management review of process performance and product quality. A PQR that is never discussed by anyone senior enough to authorise a change is not doing the job the regulation describes.
Scope: which products, which sites, which batches
Every authorised medicinal product, including export-only products, and including products for which no batches were made in the period. A product with zero batches still had complaints, stability, changes, variations and a qualification status. The review of such a product is short, but it exists, and it says explicitly that no batches were manufactured and that the stability programme and the qualification status were reviewed.
All batches in the period, whether released, rejected or reworked. Paragraph 1.10 does not say 'a representative number' and neither should your procedure. Item (iii) makes the point explicit by asking for all batches that failed specification, and a review that samples batches cannot answer the consistency question, because the batch it left out is the one that would have shown the drift. State the batch count on the first page, reconcile it against the batch register, and say that all were reviewed.
Who owns it
The manufacturer produces it. The MAH, where different, evaluates it. The QP ensures it is timely and accurate. Production, QC, engineering and regulatory affairs supply and interpret the data. QA compiles and usually authors. Senior management receives the conclusion through management review. If your procedure names only QA, the other four owners will treat the PQR as QA's problem, and the data will arrive late and unexplained. Module 1 of the course sets out a responsibility matrix that has survived inspection at contract and MAH sites, and the rest of this site works through each part of it.