Article 10a Bibliographic Applications: How to Build Them Right

For small and mid-sized marketing authorization holders, optimizing both time and resources is critical. The prospect of obtaining approval without running new trials through an Article 10a bibliographic application is attractive. This pathway, grounded in well-established use, enables reliance on published literature rather than generating proprietary non-clinical and clinical data. 

Authorities, however, do not see Article 10a as a lighter option. They expect a complete and fully defendable marketing authorisation dossier, assessed with the same intensity as a traditional application. The only distinction lies in the origin of the evidence. 

Handled well, bibliographic applications accelerate timelines, reduce expenditure, and build credibility with regulators. Poorly constructed dossiers have the opposite effect: delays, wasted resources, and diminished trust. 

The question for every biotech executive is not whether Article 10a is an option, but whether the dossier is prepared to the standard regulators demand. 

The Legal “Trick” Does Not Mean Easy 

Well-established use is not defined solely by a product’s age. Many companies mistakenly assume decades on the market equal automatic approval under Article 10a. Regulatory authorities demand far more than simple longevity. 

The legal requirement is explicit: a substance must have been in medicinal use in the European Union for at least ten years, with efficacy and safety firmly established. In practice, the bar is higher. A compliant dossier must present comprehensive evidence across pharmacology, efficacy, and safety, supported by a critical review of the literature. 

What regulators look for in practice: 

1. Clear proof that the substance has been extensively used in the EU, not just marketed. 
2. Balanced literature covering benefits and risks, including long-term safety and special populations. 
3. Evidence that directly underpins the proposed indication, dosage, and route of administration. 
4. Clinical and non-clinical overviews that build a narrative aligned with the SmPC. 

Misinterpreting well-established use as “time served” is a costly mistake. What matters is whether the published evidence convincingly supports the product under review. 

Dossier Architecture: Why Bibliographic Still Means Full CTD 

Bibliographic does not mean abbreviated. An Article 10a bibliographic application must still be filed as a full Common Technical Document (CTD). Modules 4 and 5 are built from scientific literature rather than company-owned studies, but the dossier’s structure and quality expectations remain unchanged. 

Regulators do not relax their expectations. They want the same structure, clarity, and critical analysis as in any other submission. If the dossier is incomplete or misaligned, it will not even pass validation. The scientific discussion never begins. 

 The takeaway is straightforward: bibliographic dossiers are complete dossiers. Substituting literature for proprietary data does not reduce the responsibility to deliver a coherent, fully compliant CTD. 

Literature Strategy: Where Most Applications Collapse 

Literature is the backbone of an Article 10a bibliographic application. Regulators assess not only which studies you cite but also how you select and interpret them. A dossier built on selective references or unsupported claims will quickly unravel. 

Do’s: What Strengthens Your Dossier 

• Conduct systematic searches: Follow PRISMA-S or equivalent standards to ensure every inclusion and exclusion is traceable. 

• Cover the full spectrum: Present data on efficacy, safety, special populations, and long-term use to demonstrate balance. 

• Link to your product: Show precisely how the literature supports your formulation, indication, and route of administration. 

• Deliver critical overviews: Module 2 should interpret and evaluate evidence, rather than simply summarizing publications. 

Don’ts: What Jeopardizes Your Application 

• Avoid cherry-picking: Selective evidence undermines credibility. 

• Do not present a “reading list”: Without synthesis, references carry no weight. 

• Never ignore data gaps: Acknowledge limitations and explain the mitigation strategies. 

• Do not compromise quality: Regulators expect the same standards as in a traditional CTD. 

A disciplined literature strategy signals maturity and seriousness. It demonstrates that the company is building a defensible evidence base, not simply recycling published papers. 

Example Pitfalls 

Most Article 10a bibliographic applications fail not because the science is weak but because the dossier strategy is flawed. The cost to you is measured in lost time, higher expenses, and reduced credibility. 

Submitting a Reading List Instead of a Dossier 

If you submit a package that includes references but lacks integration, analysis, or narrative, regulators will likely refuse validation. You will spend months rebuilding Module 2 and miss your procedural window. 

Overlooking Safety Gaps 

If you rely solely on strong efficacy data and ignore missing safety information, regulators will halt the process. You will be required to conduct a comprehensive gap analysis, which will drain resources and delay your program. 

Writing Overviews Without Analysis 

If your clinical overview only repeats results without interpretation, regulators will challenge your SmPC. The review will stall, and investor confidence will erode as timelines are extended. 

If you treat Article 10a as a shortcut, you set yourself up for failure. To succeed, you need to integrate the evidence, address the gaps, and present a dossier that can withstand scrutiny. 

Strategic Benefits When Done Right 

An Article 10a bibliographic application is a strategic opportunity, and when built properly, it creates speed, efficiency, and confidence across the product lifecycle. The main benefits? 

1. Reduced time-to-market: Literature-based evidence eliminates the need for new trials, thereby streamlining the process and reducing the time required for market entry. 
2. Lower development costs: Budgets can be redirected to commercial activities or pipeline growth. 
3. Enhanced investor confidence: Strong dossiers demonstrate foresight, governance, and control. 
4. Smoother regulatory reviews: Systematic evidence presentation results in fewer objections and faster approvals. 
5. Lifecycle flexibility: The literature base can support variations, extensions, and new indications without requiring a restart of development. 

When executed correctly, bibliographic submissions are not only efficient, but they also reinforce a company’s reputation as disciplined and reliable. 

From Shortcut to Strategy 

Bibliographic dossiers succeed only when they are treated as comprehensive regulatory strategies. The outcomes tell the story. Superficial dossiers filled with references and assumptions collapse under scrutiny, costing time, money, and credibility. Strong bibliographic applications, designed around systematic literature, full CTD compliance, critical interpretation, and finally taking into account local country specific expectations, achieve faster approvals, protect budgets, and build confidence with both regulators and investors. 

Treat Article 10a as an administrative shortcut and risk preventable delays. Treat it as a strategic investment and secure both speed and trust. Partnering with experienced specialists ensures that the dossier is not only compliant but also persuasive. 

At Insuvia, we help biotech companies design bibliographic applications that meet regulatory standards, protect timelines, and transform well-established use into a strategic advantage. We don’t regard bibliographic applications as shortcuts but a test of discipline. Companies that approach them strategically turn a regulatory requirement into long-term value.