A generic marketing authorisation application rests on a single scientific bridge: proof that your product behaves in the body the way the reference product does. Since 25 January 2025 that bridge has been built to an internationally harmonised specification, ICH M13A. The harmonisation is real and welcome, but the EU-specific rules that sit around it have not gone away, and they are where most applicants lose time.
What an Article 10(1) application actually asks of you
Under Article 10(1) of Directive 2001/83/EC, an applicant may omit the results of pre-clinical tests and clinical trials by demonstrating that the product is a generic of a reference medicinal product authorised in a Member State or in the Union for not less than eight years. A generic medicinal product is defined as having the same qualitative and quantitative composition in active substances and the same pharmaceutical form as the reference product, with bioequivalence demonstrated by appropriate bioavailability studies.
Two clocks run in parallel, and confusing them is a common planning error. The eight-year data protection period governs when you may file. A further two years of market protection means the generic may not be placed on the market until ten years have elapsed from the initial authorisation of the reference product.
What ICH M13A changed
ICH M13A (EMA/CHMP/ICH/953493/2022) took legal effect in the EU on 25 January 2025, together with a dedicated questions-and-answers document (EMA/CHMP/ICH/325575/2024). It supersedes the applicable parts of the former EMA Guideline on the Investigation of Bioequivalence dealing with study considerations and data analysis for non-replicate study designs. EMA has additionally published a paper on considerations for implementing M13A in the EU (EMA/531548/2024).
The central statistical test is unchanged: the 90% confidence interval for the ratio of geometric means between test and reference must fall within 80.00-125.00% for the primary pharmacokinetic parameters. What M13A harmonises is everything around that number, including study design defaults, subject selection, sample collection and data handling, so that one well-designed study can support submissions across ICH regions rather than being repeated for each. Biopharmaceutics Classification System-based biowaivers already sit separately under ICH M9.
Where EU-specific requirements still apply
- Narrow therapeutic index products. The EU continues to apply a tightened acceptance interval of 90.00-111.11% for AUC, and in defined cases for Cmax. M13A does not remove this expectation.
- Comparator sourcing. The reference product used in the study must be appropriately sourced and fully traceable. Purchase records, certificates of analysis and batch documentation are assessed, and gaps here are difficult to repair retrospectively.
- Product-specific guidance. EMA product-specific bioequivalence guidance remains in force and must be read alongside M13A, not instead of it.
- Additional strengths. ICH M13B, covering biowaivers for additional strengths, was released for consultation as a Step 2b draft (EMA/CHMP/ICH/85092/2025) between 9 April and 9 July 2025. Until it is finalised and takes effect, strength-biowaiver arguments must still be built on existing EU guidance.
Where generic dossiers lose time
- Comparator documentation assembled after the study rather than during it.
- Clinical and bioanalytical sites selected without checking their GCP and GLP inspection history.
- The bioequivalence study written up in isolation, rather than integrated into a coherent Module 2 and Module 5 narrative.
- Formulation differences, particularly excipients with a recognised action or effect, that are not justified against the reference product.
- Product information that is copied from the reference SmPC without deliberate handling of indications or sections that must be carved out.
How PQRA helps
PQRA supports generic and hybrid applicants across the full lifecycle of an Article 10 dossier: assessing whether a bioequivalence study is required or a biowaiver can be justified, reviewing protocols and study reports against M13A and applicable product-specific guidance, building comparator sourcing documentation to inspection standard, compiling and publishing the eCTD, and managing the procedure and its questions through to national implementation in Greece and beyond.
If you are planning a generic filing for the EU or Greek market, get in touch with our regulatory team to discuss your development and submission strategy.
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