The United States (US) generics market remains one of the most competitive and tightly regulated pharmaceutical landscapes in the world. Successfully developing and commercializing a generic product requires more than technical expertise – it demands a partner who understands the regulatory environment, has proven development and manufacturing capabilities, and can navigate the complexities of scale-up and market entry.
At Douglas CDMO, we’ve built a long-standing commitment to supporting our partners through this process, with a focus on quality and reliability and a deep understanding of what it takes to succeed in the USA.
Generics are growing in complexity
The US Food and Drug Administration (FDA) defines a generic drug as one that is identical or bioequivalent to a brand name drug in dosage form, safety, strength, administration route, quality, performance characteristics, and intended use. Broadly speaking, generics can be categorized as follows:
- Simple generics: typically copies of small-molecule drugs that are chemically identical to the brand name product.
- Complex generics: may involve more challenging active ingredients, non-standard formulations and dosage forms, or alternative administration routes.
Generic drugs play an important role in modern healthcare, improving access, and driving cost savings across the USA. Although they have long been viewed as straightforward, low-cost alternatives to brand name products, the reality of bringing a generic to market has grown significantly more complex. This shift is driven by a range of factors: the increasing prevalence of complex generics, tighter regulatory scrutiny, and heightened competition across nearly every therapeutic category.
Developing complex generics is rarely simple. Products such as softgels, modified-release formulations, inhaled therapies, or injectables often require specialized formulation strategies, advanced analytical methods, and tightly controlled manufacturing processes. Achieving and demonstrating bioequivalence for these products can be technically challenging and resource intensive, particularly when brand name products include proprietary delivery technologies or poorly soluble compounds.
In parallel, the FDA continues to raise expectations around product quality, process validation, and data integrity. The Abbreviated New Drug Application (ANDA) regulatory pathway has become more demanding, with increased emphasis on demonstrating not just similarity but also consistency and reliability across the product lifecycle.
Compounding these technical and regulatory pressures is the commercial reality of shortened exclusivity windows and first-to-file competition. Sponsors often have a narrow window to launch, and delays in development, scale-up, or approval can mean a missed opportunity. In this evolving landscape, success relies not only on scientific and operational excellence but also on the ability to manage risk, respond quickly to regulatory feedback, and execute with precision at every stage of development.
The role of the CDMO in generic development success
As the complexity of generic drug development grows, so too does the demand for specialized expertise, infrastructure, and regulatory understanding. Chris Cuthbertson, Program Manager of Pharmaceutical Development at Douglas CDMO, talks about the value that contract development and manufacturing organizations (CDMOs) bring to generic drug developments:
“Many drug developers are turning to CDMOs, not just as service providers, but as strategic partners for navigating the path to US market entry. As a CDMO we can provide specialized expertise with end-to-end support where and when a project needs it. We can help companies or investors de-risk development, meet regulatory expectations, and accelerate time to market without the overheads needed to support their own expert team. At Douglas, that support is grounded in years of hands-on experience with generic formulations, regulatory pathways, and commercial scale-up for the US market.”
Laying the foundation: reverse engineering and formulation strategy
The development of a successful generic product begins long before scale-up or regulatory submission. For complex dosage forms such as softgels, early formulation work hinges on understanding the composition and performance of the reference product – a process that is as much science as it is strategy.
“Formulation development often starts with reverse engineering the reference product,” says Chris. “We look closely at the innovator’s product attributes, from excipient function through to dissolution behavior, to understand what makes the formulation perform the way it does.”
This early-stage work informs every step that follows. By carefully characterizing the reference product, CDMOs can design formulation strategies that achieve therapeutic equivalence while accounting for bioavailability, stability, and manufacturability. All these factors are particularly important for complex generics that have a poorly soluble or moisture-sensitive active pharmaceutical ingredient (API).
Selecting the right API supplier with access to a high-quality Drug Master File (DMF) can significantly streamline the development process. The DMF provides essential details about how the API is manufactured, tested, and controlled, and they also hold regulatory weight.
“We review each supplier’s DMF internally to make sure it’s up to standard. If the FDA hasn’t reviewed it before, that can slow everything down – especially if they raise questions during your submission. We use these master files to understand how the API is made, its key quality attributes, and the stability profile. These documents can give us a solid technical foundation for formulation and analytical development.”
To mitigate risk, Douglas CDMO often engages multiple API suppliers during early development.
“You might have three or four options, but typically one becomes the lead – the one you trust to deliver consistently and meet regulatory requirements,” Chris explains.
Chris Cuthbertson, Douglas CDMO
Core considerations: bioavailability and stability
Achieving bioavailability and stability is one of the most demanding aspects of generic drug development, particularly for softgels. These formulations often involve poorly soluble APIs, complex excipient interactions, or sensitivity to light, heat, or oxidation. A skilled CDMO plays a vital role in navigating these challenges through early characterization, iterative testing, and targeted formulation strategies.
Bioavailability begins with understanding the physical form of the API. Polymorphic variation and particle size can influence solubility and dissolution rate, which may directly affect absorption.
“The physical form – whether crystalline or amorphous – can significantly impact solubility, stability and bioavailability,” explains Chris. “We characterize this from the start to guide formulation development. A smaller particle increases surface area and improves dissolution, but for generics we must match – not exceed! – the innovator’s release profile to ensure bioequivalence.”
Stability is addressed through early excipient compatibility studies and stress testing under light, heat, humidity, and oxidation. These tests identify degradation pathways and help inform both formulation and packaging strategies.
‘We would then determine if a stabilising excipient, an antioxidant or a chelating agent is required, or if a product needs to be protected from light or moisture, and what packaging is required,” says Chris.
The final test is performing stability studies under International Council for Harmonisation (ICH) guidelines on the lead formulation, lab scale, scale up batches and on exhibit batches to determine product shelf life.
Final stability is confirmed through studies across laboratory, scale-up, and exhibit batches, aiming for a two-year shelf life or greater. Although the target is always to match the innovator, each product presents unique technical hurdles, making early planning and scientific insight critical to success.
“If a drug is light sensitive, we’ll need to take protection into consideration at both the manufacturing and packaging stages. It’s commonly assumed that a generic will copy the innovator’s packaging, but if the formulation differs, so might the packaging requirements.”
CHRIS CUTHBERTSON, PROGRAM MANAGER OF PHARMACEUTICAL DEVELOPMENT, DOUGLAS CDMO
Accuracy matters: inside analytical development and validation
Analytical method development is another cornerstone of generic drug success. The FDA expects validated, product-specific methods that meet high standards for accuracy, precision, and specificity when approving generics. At Douglas CDMO, method development begins early, often in parallel with laboratory-scale formulation, to ensure accurate and reliable results from the outset.
For any generic drug bound for the US market, analytical method development typically begins by checking whether a pharmacopeial method – such as one published by the United States Pharmacopeia (USP) – exists for the active ingredient or finished product. These standardized methods provide a strong starting point but often require adaptation to suit the unique properties of a new formulation.
“If there’s a USP monograph, that’s a great place to start,” says Chris. “But often you need to adapt the method to work for your formulation – especially with low dose softgels where excipients can interfere with assay accuracy.”
Once a lead formulation is identified, Douglas will perform pre-validation where method performance is evaluated against set criteria. This is also applied to stability samples to detect potential interferences over time. Final validation aligns with international and US regulatory guidance and is executed on scale-up batches to ensure regulatory compliance.
Having an integrated development team onsite accelerates this process. “Our formulation and analytical team work side by side,” says Chris. “We’re able to rapidly test prototype formulations, problem solve, adapt, and transfer methods because communication is direct. That’s a real advantage.”
The right CDMO partner can make all the difference
In the complex world of US generics, success is rarely about any single milestone, it’s about execution across the entire lifecycle. From formulation design and analytical method validation to regulatory strategy and commercial scale-up, each step requires deep expertise, proactive problem-solving, and seamless integration.
Ultimately, the value of a CDMO lies not just in capacity but also in capability. The right partner will guide formulation strategy, accelerate development, ensure regulatory alignment, and deliver manufacturing excellence while maintaining an unwavering focus on quality and patient safety.
“At the end of the day, track record matters,” says Dan. “You want a partner that’s done it repeatedly and knows how to get it right the first time.”
With decades of experience in ANDA development, an end-to-end model, and a deeply embedded culture of quality by design, Douglas CDMO offers more than just infrastructure; it offers insight, reliability, and true collaboration. With over 10 generic products already commercialized in the USA, Douglas CDMO brings a proven track record to the table. For pharmaceutical companies navigating the high-stakes US generics market, that kind of partnership isn’t just a competitive advantage, it’s a strategic necessity.
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