Formulation Development Process for Injectables: Your Steps to Success [Graphic]

Formulation development can take as long as three U.S. presidential terms. With that kind of time, it’s important to understand the process. 

Whether you’re the world’s largest drug sponsor or a virtual operation, the steps to developing an injectable formula are the same. However, there are some factors that could make the process look very different for you. In this blog, we’ll cover the pros and cons of injectable formulations, what components are typically included, and how to move from concept to FDA approval.

Pros and cons of injectable drug formulations

Like any other type of drug, injectable formulations come with their own set of advantages and challenges. Understanding them can help you better navigate the formulation process. 

Pros 

Higher potency: Injectable drug formulations often exhibit higher potency compared to other drugs, like pills or patches. This can lead to faster-acting treatment, making them ideal for conditions requiring immediate effect. 

Less Active Pharmaceutical Ingredient (API): Though it sounds like a contradiction, injectable drugs also typically require less API — the ingredient responsible for a drug’s reaction. Oral or transdermal formulations, for example, require more API because some of it is lost when traveling through the GI tract or skin. Injectables are the most direct form of drug delivery — bypassing the body’s natural barriers. For that reason, they require less API to be effective.  

Reduced side effects: Oral medications interact with the GI tract, potentially causing irritation, nausea, or digestive issues. Similarly, transdermal patches can cause skin reactions, such as redness, itching, or dermatitis. By directly delivering the medication into the bloodstream, injectables avoid these routes, thereby reducing the likelihood of those side effects. 

Cons

Higher patient risk: However, bypassing the body’s natural defense systems also has a downside. If an injectable formulation is not thoroughly studied and vetted, it can lead to serious infection. Injectable drugs must be developed with stringent quality standards, leaving no room for contamination. 

More complex regulations: Because injectables require a more sterile environment, agencies like the FDA impose stricter regulations to ensure the formulation is safe for patients. This can lead to additional steps in the process and longer development timelines. 

3 key pharmaceutical formulation pathways

Not every drug that hits the market is brand new. In fact, most development projects involve making generic versions of branded drugs or developing the same drug in a different format. Depending on which type you’re working on, your pathway through formulation development will vary. 

New Drug Application (NDA)

• Extensive research and development: This pathway involves significant investment in research and development, including multiple phases of clinical trials.
• Thorough FDA review: The FDA rigorously reviews all aspects of the drug, from manufacturing processes to clinical trial outcomes and labeling.
• Market exclusivity: Successful NDA approval often grants the developer a period of market exclusivity, providing a competitive advantage.

505(b)(2)

• Reduced development time and cost: By relying on existing research, the 505(b)(2) pathway can significantly reduce the time and cost associated with drug development.
• Innovative modifications: This pathway encourages innovations such as new delivery methods, improved formulations, or new therapeutic uses for existing drugs.
• Flexibility in data requirements: Sponsors can submit data from published literature or studies not conducted by the application sponsor, enhancing flexibility and efficiency.

Abbreviated New Drug Application (ANDA)

• Bioequivalence: This means that a generic drug must be as safe and effective as the previously branded drug. 
• Cost-effective: The ANDA pathway is far less expensive than the NDA pathway, making it attractive for companies producing generic versions of drugs.
• Faster time to market: Without the need for extensive clinical trials, generics can reach the market more quickly, providing affordable alternatives to branded drugs.

Each of these formulation pathways — NDA, 505(b)(2), and ANDA — offers unique advantages and challenges. Choosing the right pathway depends on the nature of the drug, the available data, and the strategic goals of the development program. 

Key steps in the formulation development process 

The journey to bring an injectable drug from concept to market takes years. This can vary depending on whether the drug is a New Drug Application (NDA), Abbreviated New Drug Application (ANDA), or 505(b)(2) application, but the key steps remain the same. 

Concept and feasibility

The process begins with a concept. Maybe you’ve discovered that a particular molecule excites another in a promising way. Or maybe the market exclusivity on a branded drug has expired, and you need to create a generic version. Either way, the initial idea is articulated, supported by preliminary research and small-scale laboratory experiments. For NDA drugs, this involves extensive novel research, while 505(b)(2) and ANDA drugs leverage existing data. Feasibility studies are conducted to assess the potential effectiveness of the proposed formulation.

Preformulation

In the preformulation phase, the physical and chemical properties of the Active Pharmaceutical Ingredient (API) and excipients are thoroughly studied. This phase aims to understand the drug’s behavior, stability, and compatibility with other formulation components. Again, for 505(b)(2) and ANDA applications, existing data can streamline this process, reducing the need for extensive new studies.

Formulation development

Next is formulation development, where the drug’s final formulation is designed. This step includes optimizing the ratio of API to excipients, conducting proof-of-concept studies, and developing analytical methods.

Manufacturing

Once the formulation is finalized, it is time to create enough of the drug for clinical trials. Often, the manufacturing process can be as complex as the formulation itself. The FDA requires strict guidelines to ensure the drug does not get contaminated or altered during manufacturing.

Clinical trials

The formulated drug then undergoes clinical trials to evaluate its safety and efficacy in humans. This phase is critical for gathering the data required for regulatory approval. NDA drugs generally require extensive multi-phase trials. 505(b)(2) drugs might leverage existing clinical data supplemented with bridging studies. ANDA drugs typically require bioequivalence studies to demonstrate they perform similarly to the reference drug, focusing more on comparative data and less on new testing.

Regulatory submission

After successful clinical trials, the next step is regulatory submission. All your data about the drug’s development, manufacturing, and clinical trials is submitted to the FDA. This must demonstrate the drug’s safety, efficacy, and quality.

FDA approval

Finally, the FDA reviews the submission and, if satisfied with the evidence presented, grants approval for the drug to be marketed. This approval signifies that the drug meets all regulatory standards and can be safely used by patients. 

It's important to note that this process can be iterative. For example, the FDA may require more trials after your submission, or you may need to revisit your excipients. Each of these steps is vital for ensuring that the injectable drug formulation is effective, safe, and ready for use in the medical field.

Benefits of partnering with a CDMO for formulation development 

When it comes to developing injectable formulations, partnering with a Contract Development and Manufacturing Organization (CDMO) offers a lot of benefits. These advantages can impact both the efficiency and success of your drug development process.

Reduced financial risk

The same reason you might outsource HR or IT is why you should partner with a CDMO. Because the alternative is to pay for everything yourself. By working with a CDMO, you get access to everything you need without the massive investment. Even the world’s largest drug sponsors work with CDMOs. Especially when it comes to new drugs, formulation development is not a guaranteed process. You may invest years into the process only to find that the drug won’t work. Working with a CDMO helps protect you from that loss and ensures you can quickly pivot to the next thing.

Niche expertise

CDMOs work with lots of different drug sponsors. While they strictly protect intellectual property, CDMOs do gain expertise from working on a wide breadth of projects. That context can be crucial for making breakthroughs in your drug’s development. It can also speed your process along significantly. Plus, their expertise in project management and operations can help you avoid roadblocks along the way.

Access to advanced technology

In addition to expertise, you can access advanced technology through a CMDO. This can be one of the most expensive parts of drug development — with single pieces of equipment costing hundreds of thousands of dollars. With CDMOs specializing in formulation and manufacturing, you can focus on bringing new drugs to market. 

Find the right CDMO for your formulation

From chemical components to delivery to regulatory pathways, formulating injectable drugs is a complex process. That’s why you need a partner who’s in it for the long haul. 

Whether you have a new, adapted, or generic drug to develop, American Injectables can help. As a nimble CDMO based in the USA, we are built on transparency, flexibility, and quality. Sound good? Our actions are even better. Learn more about our end-to-end services, and set up a call to connect with our team.