Strategic Choices That Define a Biotech’s Path to the Clinic: First-in-Human Is Earned Long Before It Begins

A Target Product Profile (TPP) is not a nice-to-have slide for investors — it is the anchor that connects the underlying biology to regulators, clinicians, and future payers. When the intended use or patient population is vague, everything downstream starts to drift: nonclinical scope expands, endpoints multiply, and CMC priorities lose focus.

In contrast, a clear and credible TPP enables disciplined decision-making across development, from sequencing milestones to positioning the program around a rare disease path, an unmet-need strategy, or a broader indication.

So what?

Developers who define the TPP early build programs that are coherent, efficient, and strategically aligned, while those who do not risk chasing data without a clear path to approval or value.

The legal basis for authorisation — whether as an originator or a biosimilar — is not a downstream choice. Together with product classification, it determines the dossier that must be built and the data needed to support development.

Whether a product is developed as a new entity or relies on approved reference products directly shapes the required preclinical, CMC, and clinical programmes. For biosimilars, similarity must be demonstrated against the locally authorised reference product, making reference product strategy inherently region specific and requiring either access to representative material in each target market or an agreed bridging approach.

With rapidly evolving technologies, many products no longer fit neatly into traditional regulatory classifications, and regulatory expectations — particularly for nonclinical and clinical evidence — continue to evolve and differ across regions. In some jurisdictions, in vivo animal studies may be reduced where analytical and functional similarity is sufficiently convincing, or not required at all.

If the regulatory route and product classification are not defined early, development plans tend to drift — generating data that may be scientifically sound but inefficient, insufficient, or misaligned with what regulators will ultimately expect.

So what?

Early clarity on product classification and regulatory route helps developers entering the clinical stage ensure that preclinical, CMC, and clinical programmes generate the right evidence across regions — avoiding costly rework and late-stage surprises.

Early engagement with regulatory agencies through scientific advice is one of the most effective ways for developers to move programs forward with confidence. This engagement works best when developers are clear on four questions: what input is needed on the development plan, when advice should be sought before decisions become costly or irreversible, where to engage across jurisdictions, and why the interaction is critical — to reduce uncertainty, avoid missteps, and keep development aligned with a credible path to approval.

Regulatory agencies offer different scientific advice options depending on the stage of development and the type of product, each with distinct scope, requirements, timelines, and outcomes. Choosing the right mechanism at the right time is therefore as important as the questions being asked.

So what?

Developers who engage early and strategically can de-risk development and make better-informed decisions, while those who delay often discover regulatory misalignment only after time, money, and options have already been spent.

In early development, CMC can feel like an expensive distraction from the science, but CMC decisions made too late are among the hardest and costliest to fix, particularly for biologics. Regulatory expectations, including those reflected in ICH quality guidance, increasingly focus on early process understanding, risk-based control, and clear documentation to support CTAs or INDs, even at early stages.

The real challenge is not whether CMC work is needed, but how much is needed now versus later. A fit-for-purpose strategy means being clear early on about what must be defined and controlled from the start — such as critical quality attributes, key process parameters, and comparability principles — while deliberately leaving room to optimise and scale after first-in-human.

So what?

Developers who get this balance right meet regulatory expectations without over-engineering early manufacturing, while those who do not often pay for it later through delays, rework, or avoidable regulatory risk.

Putting the right quality and safety foundations in place early is about control and accountability, not bureaucracy. Quality ensures that data, vendors, and development decisions are reliable and traceable; safety ensures that risk is actively assessed and owned as programs move toward human exposure.

For early developers, this does not mean building a full pharmaceutical QMS or a heavy pharmacovigilance organisation. Practical, fit-for-purpose options exist, including lean GxP governance, defined safety responsibilities, scalable processes, and outsourced or hybrid models that grow with the program.

So what?

Developers who put the right quality and safety foundations in place before FIH protect their data, their patients, and their credibility — and avoid costly delays and loss of confidence just when speed matters most.

In the EU, the Clinical Trials Regulation (CTR) and the Clinical Trials Information System (CTIS) fundamentally change how clinical trials are planned and executed. For developers, this is not an administrative detail — CTR and CTIS directly affect timelines, documentation strategy, transparency expectations, and the feasibility of running multi-country trials.

In practice, this means designing clinical programs that are operationally viable under CTIS, with submission-ready documentation, clear roles and responsibilities, and robust vendor oversight, while still meeting scientific objectives.

So what?

Under CTR and CTIS, clinical success in Europe depends as much on execution readiness as on science, and developers who fail to plan early risk delays, rework, and loss of momentum at a critical stage of development.

Financing is not separate from regulatory strategy; it depends on it. Even at the preclinical stage, funders increasingly look for credibility in the path to clinic, not just promising science. This applies to public funding programmes, such as the EU’s EIC Accelerator, US mechanisms such as NIH- or BARDA-supported translational funding, and UK schemes delivered through Innovate UK.

The same logic underpins private financing, including venture capital, corporate venture arms, family offices, strategic investors, and pharma partnerships. Increasingly, capital is released against milestones that visibly reduce regulatory risk, rather than scientific progress alone.

So what?

Developers who plan financing around regulator-relevant milestones from the preclinical stage tell a more credible story, unlock capital more efficiently, and avoid funding gaps caused by regulatory uncertainty just when momentum matters most.