1What an annual product review is.
In the US, the drug CGMP regulations require written records to be kept so that their data “can be used for evaluating, at least annually, the quality standards of each drug product to determine the need for changes in drug product specifications or manufacturing or control procedures”. Written procedures must be established and followed for these evaluations.¹ FDA’s quality systems guidance calls this the annual review.² Part 211 does not ask for the evaluation to be sent to FDA. Records required under it must be readily available for authorised inspection,¹ and the annual report an NDA holder submits to FDA within 60 days of each anniversary of approval is a separate document.³
In the EU, Chapter 1 of the GMP guide asks for “regular periodic or rolling quality reviews of all authorised medicinal products, including export only products”. Their objective is to verify the consistency of the existing process and the appropriateness of the current specifications for starting materials and finished product, to highlight trends and to identify product and process improvements. They should normally be conducted and documented annually, taking previous reviews into account.⁴ ICH Q7 asks for the same kind of review of active pharmaceutical ingredients, also normally annually.⁵
2What it must include.
21 CFR 211.180(e) names two things the procedures must provide for. EU GMP Chapter 1 lists twelve that a review “should include at least”, and ICH Q7 lists seven for APIs.¹⁴⁵
| Item | 21 CFR 211.180(e) | EU GMP 1.10 | ICH Q7 2.50 |
|---|---|---|---|
| Batches | A representative number, approved or rejected, with their records | Critical in-process controls and finished product results | Critical in-process control and critical API test results |
| Failed batches | Through rejected batches and the 211.192 investigations of specification failures | All batches that failed specification, and their investigation | All batches that failed specification |
| Deviations and investigations | Investigations under 211.192 | All significant deviations or non-conformances, their investigations and the effectiveness of the resulting CAPA | All critical deviations or non-conformances and their investigations |
| Complaints, recalls and returns | Complaints, recalls, returned or salvaged products | All quality-related returns, complaints and recalls, with their investigations | All quality-related returns, complaints and recalls |
| Starting and packaging materials | Not named | Especially new sources, and supply chain traceability of active substances | Not named |
| Changes | Not named | All changes to processes or analytical methods | Any changes to processes or analytical methods |
| Stability | Not named | Stability monitoring results and adverse trends | Stability monitoring results |
| Earlier corrective actions | Not named | Adequacy of other previous product, process or equipment corrective actions | Adequacy of corrective actions |
| Regulatory | Not named | Marketing authorisation variations submitted, granted or refused; post-marketing commitments for new authorisations and variations | Not named |
| Equipment and utilities | Not named | Qualification status of relevant equipment and utilities, such as HVAC, water and compressed gases | Not named |
| Contracts | Not named | Contractual arrangements under Chapter 7, to check they are up to date | Not named |
3How the APR and the PQR differ.
The two are different instruments. Section 211.180(e) is a US regulation, part of the CGMP rules for finished pharmaceuticals.¹ Chapter 1 is one of the EU’s detailed GMP guidelines, published under Article 47 of Directive 2001/83/EC to interpret the GMP principles in EU law.⁴ ICH Q7 is the ICH guideline for active substances.⁵
The EU review covers more and assigns more. The manufacturer and, where different, the marketing authorisation holder should evaluate the results and assess whether corrective and preventive action or revalidation is needed. Where the holder is not the manufacturer, a technical agreement should define each party’s responsibilities for producing the review. Reviews may be grouped by product type, such as solid dosage forms or sterile products, where scientifically justified.⁴ The US rule asks for the evaluation to determine the need for changes to specifications or to manufacturing or control procedures.¹
4How to prepare one.
- Set the scope. Define the products, the review period and the batch population. The US rule covers batches “whether approved or rejected”, and the EU list includes all batches that failed specification, so the population can’t be limited to released batches.¹⁴
- Collect each item. Gather the data for every row of the table above that applies to the product and market, along with the previous review.⁴
- Trend the data. ICH Q9(R1) lists selecting, evaluating and interpreting trend results within the product quality review among the potential uses of quality risk management.⁶ FDA’s guidance adds that, although the regulations require review at least annually, a quality systems approach calls for trending “on a more frequent basis as determined by risk”.²
- Conclude. State whether specifications, manufacturing or control procedures need to change,¹ and whether corrective action or revalidation should be undertaken. For APIs, document the reasons for any corrective action.⁵⁴
- Follow up. Manage the actions through the quality system, and verify the effectiveness of those management procedures during self-inspection.⁴ For APIs, agreed corrective actions should be completed “in a timely and effective manner”.⁵ The next review checks the adequacy of earlier corrective actions.⁴
The review also feeds risk management: ICH Q9(R1) lists the results of product review among the planned events that should prompt a review of earlier risk decisions.⁶
5How it runs in Seal.
In Seal’s annual product quality review, the review starts from an agreed population of product, period, sites and source domains, reconciled before anything is analysed, so rejected batches and batches still awaiting disposition stay in scope with their state at the data cut. Batch outcomes, stability, complaints, changes and supplier history are evaluated in the same product context. The reviewed evidence cut is frozen with the issued report, and each conclusion carries into an action with an owner and evidence of completion that stays visible in the next review.
Neil can prepare a product quality review draft with a coverage matrix and evidence index; the product and quality owners assess the trends and conclusions. Other recurring reports run the same way in automated reporting, each against a defined population, time window and data cut, with source versions and counting rules kept with the run.
References
- 121 CFR 211.180, General requirements (records and reports), paragraphs (c) and (e), eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ section- 211. 180 (read 6 November 2026) - 2Guidance for Industry: Quality Systems Approach to Pharmaceutical CGMP Regulations, FDA, September 2006, section IV.D.1 and glossary. https:/
/ www. fda. gov/ media/ 71023/ download (read 6 November 2026) - 321 CFR 314.81, Other postmarketing reports, paragraph (b)(2), eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ section- 314. 81 (read 6 November 2026) - 4EudraLex Volume 4, Part I, Chapter 1, Pharmaceutical Quality System, European Commission, in operation from 31 January 2013, sections 1.10 and 1.11. https:/
/ health. ec. europa. eu/ system/ files/ 2016- 11/ vol4- chap1_ 2013- 01_ en_ 0. pdf (read 6 November 2026) - 5ICH Q7, Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients, ICH, 10 November 2000, section 2.5. https:/
/ database. ich. org/ sites/ default/ files/ Q7%20Guideline. pdf (read 6 November 2026) - 6ICH Q9(R1), Quality Risk Management, ICH, adopted 18 January 2023, section 4.6 and Annex II.1. https:/
/ database. ich. org/ sites/ default/ files/ ICH_ Q9%28R1%29_ Guideline_ Step4_ 2023_ 0126_ 0. pdf (read 6 November 2026)
AQuestions and answers
What is the difference between an APR and a PQR?
APR is the US name for the annual evaluation 21 CFR 211.180(e) requires, which must cover a representative number of batches, complaints, recalls, returns and investigations. PQR is the EU name for the review in EU GMP Chapter 1, which lists twelve items, adds starting materials, stability, changes, variations, CAPA effectiveness and equipment qualification, and gives the marketing authorisation holder a role. A product supplied to both markets needs a review that covers both lists.
Is the annual product review sent to FDA?
No. Part 211 does not ask for it to be submitted. The APR is an internal evaluation, and the records required under Part 211 must be readily available for authorised inspection. It is different from the annual report an NDA holder submits to FDA within 60 days of each anniversary of approval, which includes a description of manufacturing and controls changes that did not need a supplement.
How many batches does an APR have to include?
21 CFR 211.180(e) asks for a representative number of batches, whether approved or rejected, and does not set a figure. EU GMP asks for the critical in-process and finished product results and for all batches that failed specification, with their investigations. So the review can’t be limited to released batches.
Can the review be rolling instead of once a year?
Yes in the EU, which asks for regular periodic or rolling reviews, normally conducted and documented annually. The US rule sets a minimum of at least annually, and FDA’s quality systems guidance recommends trending more often where the risk calls for it.
Who writes the PQR when manufacturing is outsourced?
In the EU, the manufacturer and, where different, the marketing authorisation holder both evaluate the results, and a technical agreement should define each party’s responsibilities for producing the review.