Validation of a Medicinal Product Manufacturing Process According to GMP – IQ/OQ/PQ Qualification and Cleaning Validation

Repeatability is the foundation of pharmaceutical manufacturing. A medicinal product manufactured today must have the same parameters as a medicinal product from the same line manufactured three months from now, by a different shift, from a different raw material delivery. The tool that provides evidence of this is process validation – documented confirmation that a process operated within established limits consistently produces a product that meets its specification.

For a brand owner commissioning contract manufacturing of medicinal products, validation is not a purely technical matter handled exclusively by the manufacturer. It determines whether the data submitted to the registration dossier will be reliable and whether the product will be consistent from the first batch to the last. This article explains what validation consists of and why it is worth asking about it when choosing a manufacturer.

Legal basis – Annex 15 to the GMP guidelines

The requirements for qualification and validation are set out in Annex 15 to the EU GMP guidelines (EudraLex, Volume 4). The current revision of this document entered into force on 1 October 2015 and shifted the focus to an approach based on the entire product life cycle and quality risk management. This means that validation is not a one-off test passed before start-up, but a continuous state maintained throughout the entire manufacturing period.

Annex 15 covers the qualification of premises, equipment, utilities and the validation of manufacturing processes. This entire system is brought together by the Validation Master Plan – a high-level document that describes the scope, strategy and schedule of all validation activities at the site. Without it, individual qualifications are merely a collection of separate reports, not coherent evidence of control.

Four stages of qualification – DQ, IQ, OQ, PQ

Equipment qualification follows a logical sequence of stages, each of which answers a different question:

• DQ (design qualification) – confirms that the design of the equipment or installation meets user requirements and GMP principles before the equipment even arrives at the site;
• IQ (installation qualification) – covers technical and installation-related aspects: it verifies whether the equipment has been installed in accordance with the documentation, specification and the manufacturer’s requirements;
• OQ (operational qualification) – verifies the logic and operation of the system across the full range of operating parameters, including its response to boundary conditions;
• PQ (process qualification) – confirms the performance of the entire process under conditions close to routine production; it is carried out after successful completion of IQ and OQ.

The revision of Annex 15 allows stages to be combined, for example IQ with OQ, or PQ with OQ or with process validation, provided this is justified and documented. This provides flexibility in the schedule, but does not remove the obligation to demonstrate that each qualification objective has been achieved. This technical arrangement has a straightforward business impact: it shortens the time needed to reach the first released batch without lowering the level of rigor.

Cleaning validation – protection against cross-contamination

In a facility manufacturing different products on shared equipment, it is essential to demonstrate that, after one batch has been completed and the line has been cleaned, no residues of the previous product, cleaning agents or microorganisms remain on it in quantities that could pose a risk to the next batch. This is the purpose of cleaning validation.

The modern approach is based on establishing scientifically justified residue limits, based on toxicological data and the permitted daily exposure value, rather than on arbitrary thresholds. Residues are checked using analytical methods applied to swabs and rinse samples, and the entire process is documented in a protocol and report. For the brand owner, this is a direct guarantee that their product will not be contaminated with traces of another active substance manufactured at the same site.

Three approaches to process validation

Annex 15 does not impose a single rigid validation scheme. The manufacturer selects the approach according to the nature of the product and the knowledge it has about the process, and this choice must be justified in the documentation. In practice, three models are encountered:

• traditional approach – validation is performed on a defined number of consecutive production batches (most often three) manufactured under target conditions before routine sales begin; this remains the most common model for generic medicinal products;
• ongoing process verification – based on continuous monitoring of production data using statistical tools; it requires a deep understanding of the process and works well in a modern Quality by Design approach;
• hybrid approach – combines elements of both of the above, using knowledge from product development where it is robust and classical validation batches where data are lacking.

Regardless of the model, before validation begins, clearly defined acceptance criteria must be in place – values that the process must achieve in order to be considered validated. Criteria established after the fact, to fit the results obtained, are a classic error that an inspector will detect immediately. A well-described validation protocol is therefore prepared before the first batch starts, not after it. The validation records themselves are subject to the same rigor as the manufacturer’s other documentation – the principles of Good Manufacturing Practice for maintaining and archiving records apply here.

What validation means for your brand

A validated process is not paperwork for the inspector, but real value for the product owner. It translates into three specific benefits: predictable quality of every batch, reliable data for the registration dossier, and resilience to product challenges during audits and inspections. A brand whose medicinal product is manufactured in a validated process runs a lower risk of holds, complaints and costly recalls. Fewer deviations also directly translate into the speed with which the Qualified Person carries out batch release for the market.

Validation is also closely linked to an earlier stage, namely technology transfer to the manufacturing site – this is when the parameters that will subsequently be validated are established. We describe the entire quality system, in which validation is one of the pillars, in more detail in the article on the role of GMP and ISO 22000:2018 certificates.

Choose a manufacturer that validates processes from the ground up

Contract manufacturing of a medicinal product in a validated environment is a guarantee of the safety and repeatability of every batch. Laboratorium Galenowe Olsztyn, part of the Eubioco group, conducts equipment qualification and process validation in accordance with Annex 15, based on a GMP certificate issued by the Chief Pharmaceutical Inspector. Are you looking for a partner who will confirm the quality of your product with hard data? Contact us at sprzedaz@eubioco.eu to discuss your project and plan process validation.

REFERENCES

1. European Commission (2015). EudraLex – The Rules Governing Medicinal Products in the European Union, Volume 4, Annex 15: Qualification and Validation. [online] Available at: https://health.ec.europa.eu/system/files/2016-11/2015-10annex150.pdf [accessed online: 15.07.2026]
2. Regulation of the Minister of Health of 9 November 2015 on the requirements of Good Manufacturing Practice (Journal of Laws of 2022, item 1273).
3. ISPE Poland Association (2015). Annex 15 Qualification and Validation has been published on the EudraLex website. [online] Available at: https://ispe.org.pl/aneks-15-kwalifikacja-i-walidacja-zostal-opublikowany-na-stronach-eudralexu/ [accessed online: 15.07.2026]
4. Act of 6 September 2001 – Pharmaceutical Law (Journal of Laws of 2022, item 2301, as amended).