Author: Site Editor Publish Time: 2026-10-22 Origin: Site
EMA Publishes Final ICH M13B Guideline: A Clearer Route to Additional-Strength Biowaivers
On 21 September 2026, the European Medicines Agency published the final ICH M13B guideline on bioequivalence for immediate-release solid oral dosage forms — additional strengths biowaiver — together with its accompanying Questions and Answers document. The draft was open for comment from 9 April to 9 July 2025; the final texts take effect in the European Union on 17 March 2027 and supersede the applicable parts of the existing EMA guidance on additional-strength waivers. Transition arrangements are still to be announced. In practice the guideline confirms a route many development teams already use: once in vivo pharmacokinetic bioequivalence has been shown for one strength, the remaining strengths in the line can be waived without further in vivo studies — provided the evidence chain holds.
EMA Publishes Final ICH M13B Guideline: A Clearer Route to Additional-Strength Biowaivers
On 21 September 2026, the European Medicines Agency published the final ICH M13B guideline on bioequivalence for immediate-release solid oral dosage forms — additional strengths biowaiver — together with its accompanying Questions and Answers document. The draft was open for comment from 9 April to 9 July 2025; the final texts take effect in the European Union on 17 March 2027 and supersede the applicable parts of the existing EMA guidance on additional-strength waivers. Transition arrangements are still to be announced. In practice the guideline confirms a route many development teams already use: once in vivo pharmacokinetic bioequivalence has been shown for one strength, the remaining strengths in the line can be waived without further in vivo studies — provided the evidence chain holds.
What ICH M13B covers
The guideline applies to orally administered immediate-release solid dosage forms intended to deliver the drug to the systemic circulation: tablets, capsules, and granules or powders for oral suspension. It applies during development and in the post-approval phase.
Where in vivo PK bioequivalence — or equivalent efficacy and safety evidence — has been established for at least one strength, additional strengths may be exempted from further in vivo PK BE studies, subject to scientific evaluation. The same principles apply when a new strength is introduced against the strength used in a pivotal clinical trial, which can serve as the biobatch strength.
The four criteria that carry the waiver
ICH M13B assesses an additional-strength waiver against four factors:
PK dose proportionality of the drug substance
qualitative and quantitative proportionality of the formulation, compared with the biobatch strength
similarity of the manufacturing process
similarity of dissolution profiles, generated under the conditions specified in the guideline
In principle, all strengths should share the same core formulation and a rational proportional composition, be manufactured by a comparable process, and be supported by appropriate multi-media dissolution data.
Deviations must be justified, not tuned
A formulation that departs from direct compositional proportionality is not automatically excluded. The guideline expects a risk-based scientific justification; Annex I sets out the considerations, and Annex III provides a decision tree for non-high-risk products.
What the guideline does not accept is a similarity result obtained by adjusting test conditions. Dissolution methods should be selected and pre-specified on scientific grounds rather than optimised once the data are in. The waiver is therefore a development decision taken early, not a submission-stage check on a dissolution table.
M13B is not a BCS waiver — and the Q&A says so
The Q&A document addresses the question raised most often during consultation: how M13B relates to ICH M9. The two operate at different levels. M9 compares a test product with a comparator product; M13B compares strengths within a single product line. An additional-strength waiver under M13B rests on in vivo data, formulation and in vitro dissolution — not on formulation and in vitro data alone.
Two consequences follow. First, M13B is not limited by BCS class, so Class II or Class IV drug substances can be considered for an additional-strength waiver. Second, this does not lower the evidence standard: the file must still explain why the additional strength behaves consistently with the strength supported by in vivo data.
The Q&A also closes a common shortcut. If the anchor strength was itself accepted on a BCS-based biowaiver under M9, it cannot then be used to waive other strengths — that would be a waiver built on a waiver, resting entirely on in vitro data.
What changes for development and regulatory teams
Bainuo's view
ICH M13B gives multi-strength products a clearer international assessment route. For projects targeting the EU and other regulated markets, the practical consequence is that waiver feasibility should be assessed at candidate selection and during formulation development — not assembled shortly before filing.
Four elements are worth fixing early:
the anchor strength, and the batch retained for later comparative dissolution testing
the formulation and process rationale that will support proportionality across the range
the dissolution method, including media and conditions, specified before results are generated
the sample quantities and batch records that let a reviewer trace each strength back to the in vivo anchor
For applications and variations timed around 17 March 2027, the file should also state which framework it relies on, since the current EMA provisions on additional-strength waivers are superseded on that date.
Bainuo will continue to track the ICH M13 series and the EMA's implementation and transition arrangements, and will reflect these technical expectations in its formulation development and regulatory filing practice.
FAQ
When does ICH M13B take effect?
In the European Union on 17 March 2027. From that date it supersedes the applicable parts of the current EMA guidance on additional-strength biowaivers; the EMA has said that EU-specific implementation and transition considerations will be published separately.
Does M13B apply to BCS Class II or Class IV drugs?
Yes. Because the waiver rests on in vivo evidence for at least one strength plus formulation and dissolution data, it is not restricted by BCS class. The justification burden, however, is unchanged.
Can a strength approved under an M9 BCS-based waiver anchor an M13B waiver?
No. The Q&A states that a waiver of an additional strength based on a strength accepted through a BCS-based biowaiver is not acceptable — it would be a waiver on a waiver, based only on in vitro data.
Which dosage forms are in scope?
Immediate-release solid oral dosage forms acting systemically — tablets, capsules, and granules or powders for oral suspension — during development and post-approval.
Conclusion
ICH M13B does not invent a new pathway so much as formalise one and raise the standard of evidence attached to it. The teams that benefit are those that treat the strength range as a single design problem — one anchor batch, one formulation logic, one dissolution method — rather than a set of separate filings.
