Double source excipients early?

For decades, pharmaceutical formulation scientists have treated excipients as relatively straightforward ingredients: standardized, pharmacopeial materials sourced from trusted suppliers and incorporated into robust formulations. But that assumption is increasingly under pressure.

From pandemic-era supply chain shocks to geopolitical instability, raw material shortages, freight disruptions, and evolving regulatory expectations, the pharmaceutical industry has learned a difficult lesson: excipients are no longer just “inactive ingredients.” They are strategic components of product performance and supply continuity.

Yet despite these realities, many drug developers still begin formulation work with a single excipient supplier postponing dual sourcing considerations until late-stage development or even after commercialisation. Why is this still the case and can / should this not be changed?

In this short article we would like to question the status quo and ask where the industry currently is and where it is heading to. Thanks for joining the conversation in the comments. The content shared is more food for thoughts and a baseline for exchange.

The hidden cost of single sourcing

On paper, single sourcing appears efficient. Development teams move faster, formulation screening becomes simpler, and procurement relationships are streamlined. Especially in early development, companies often prioritise speed and cost containment over supply chain resilience.

But the apparent simplicity can become expensive later.

When an excipient supplier changes manufacturing sites, experiences quality deviations, receives regulatory observations, or simply cannot meet commercial demand, pharmaceutical companies may suddenly face a difficult reality: switching excipient sources is rarely as simple as replacing one material with another.

Even pharmacopeially compliant excipients can behave very differently in formulations. Potential differences in:

• particle size distribution
• bulk density
• moisture content
• surface morphology
• compaction behavior
• impurity profiles
• substitution levels

can significantly impact manufacturability and product performance.

For modern dosage forms particularly direct compression tablets, modified-release systems, poorly soluble APIs, and continuous manufacturing processes those differences can become critical.

“Pharmacopeial equivalence does not necessarily mean functional equivalence,” has become a familiar phrase among formulation scientists.

Why early double sourcing can change the equation

Companies that evaluate multiple excipient suppliers during formulation development gain advantages that extend far beyond procurement flexibility. By incorporating secondary sources early, development teams can:

• understand functional variability
• define broader design spaces
• improve formulation robustness
• reduce future change-control burdens
• simplify lifecycle management
• strengthen regulatory filings

Most importantly, they avoid one of the industry’s most expensive scenarios: introducing a second excipient supplier after product approval. Late-stage supplier changes can trigger:

• bridging studies
• additional stability work
• process revalidation
• regulatory variations
• comparability assessments
• and sometimes bioequivalence concerns

For globally marketed products, these activities can consume significant time and resources across multiple regulatory regions. In contrast, developers that proactively qualify multiple suppliers early can build flexibility directly into their regulatory strategy.

So why isn’t the industry doing it more often?

Despite the benefits, widespread adoption of early dual sourcing remains limited. The reasons are both practical and cultural.

Development speed still dominates decision-aking

In competitive pharmaceutical development environments, teams are rewarded for accelerating timelines. Adding a second excipient supplier during formulation work immediately increases:

• experimental complexity
• analytical testing
• stability requirements
• procurement coordination
• documentation workload

For companies under pressure to reach clinical milestones quickly, dual sourcing can appear like an unnecessary complication. Sometimes it is also a simple procurement issue to get another source as “not yet listed” in the system making cost and time a killer criteria.

“In early development, people often optimise for speed, not resilience,” says one formulation consultant. “The supply chain problems feel hypothetical until they become very real.”

Increased development complexity

You may need:

• more formulation work
• larger DoE matrices
• additional analytical characterization
• more stability batches

Higher early development cost

Costs increase because:

• two suppliers must be qualified
• more material testing is required
• procurement complexity increases

For early-stage or virtual biotech companies, this may be difficult financially.

Potential variability risks

If the formulation is highly sensitive, introducing multiple excipient sources may:

• increase variability
• complicate process optimization
• require tighter controls

Sometimes a formulation only works robustly with a very specific excipient grade/source.

Budget constraints push risk into the future

Small biotech firms and virtual development companies often operate with limited budgets. Their focus is typically on demonstrating proof-of-concept and securing investment, not long-term supply chain optimisation. As a result, excipient sourcing strategies are frequently deferred.

The assumption is that supplier flexibility can be addressed later although later often becomes significantly more expensive. The similar thinking exists on the formulation strategy in general. Often an initianl, non-optimised formulation will not be touched again and might be “pushed through” till the market.

Procurement and formulation teams are still too separate

Another challenge is organisational. Excipient sourcing decisions often sit between:

• formulation development
• procurement
• quality assurance
• regulatory affairs
• and supply chain management

In many organisations, these functions still operate in silos. Formulators may prioritise technical performance, while procurement focuses on cost and commercial contracts. Strategic supplier risk management is not always integrated into early development decisions.

The industry still underestimates excipient complexity

Historically, excipients were viewed as interchangeable commodities. That mindset persists in parts of the industry despite increasing evidence that excipient variability can directly influence:

• dissolution
• content uniformity
• tablet hardness
• manufacturability
• long-term stability

Modern formulations have become more sophisticated, but sourcing strategies have not always evolved at the same pace.

Regulators are quietly raising expectations

Regulatory agencies are also shifting their perspective. Guidelines aligned with:

• International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Q8,
• International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Q9,
• International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Q10,

increasingly emphasise topics like material understanding, risk management, critical material attributes and supply continuity.

Health authorities now expect companies to better understand how raw material variability impacts product quality. That expectation naturally favours companies that characterise multiple excipient sources early rather than reacting to problems later.

A Strategic shift Is emerging

The industry is unlikely to abandon single sourcing overnight. For certain specialised excipients, true dual sourcing may not even be possible. But attitudes are changing.

Many companies are now adopting hybrid strategies:

• developing initially with a preferred supplier
• while screening secondary sources in parallel
• including alternative suppliers in robustness and stability studies before commercialisation.

The approach reflects a broader industry realisation: excipient sourcing is no longer just a procurement issue. It is now a formulation strategy, a regulatory strategy, and increasingly, a business continuity strategy.

In an era where supply chain disruptions can halt production globally within weeks, the cost of dual sourcing early may ultimately be far lower than the cost of discovering too late that a “simple” excipient was never truly interchangeable after all.

As mentioned at the beginning this text is to be considered as “food for thoughts” and exchange on this important topic. Being mainly a risk-cost-reward estimation which in my opinion should be done at a very early stage. In many cases it is not possible to start with dual sourcing of main components but the risk-benefit evaluation should be done and decisions based on it. What do you think?

See Philippe Tschopp´s original post here

Source: Philippe Tschopp, LinkedIn article (45) Double source excipients early? | LinkedIn