Small molecule drugs have the most prominent outsourcing history in the pharmaceutical world.

Years ago, choosing a small-molecule drug substance partner was considered a simple client-vendor relationship, where the entire focus was on identifying supply chain inefficiencies, improving production, and cost reduction. Over the years, this simple relationship has flourished into genuine partnerships, with pharmaceutical companies now focusing on accessing advanced technologies and scientific expertise of other companies through outsourcing.

In this article, we will specifically focus on criteria for selecting a small-molecule drug substance partner. But before that, it is important to understand what small molecule drugs are and how they are discovered and developed.

So, without further ado, let’s begin.

What are Small Molecule Drugs?

As the name indicates, Small Molecule Drugs are drugs with low molecular weight, typically under 900Da. Due to their small size, these drugs can move through the body easily and permeate through cell membranes to reach intracellular targets.

Small molecule drugs comprise 90% of all pharmaceutical drugs and are ideal candidates for devising targeted therapies, thanks to their simple chemical structures. For example, small molecules can be incorporated into novel chemotherapeutics to inhibit certain proteins in cancer cells.

Insulin, aspirin, and antihistamines are popular examples of small-molecule drugs.

Small molecule drugs can be administered as oral tablets and capsules, inhalers, suppositories, or injectables.

The Drug Development Process

The drug development process of small molecule drugs is complex, requiring the expertise of researchers from chemistry, biology, drug discovery, computer science, and informatics – with the entire process taking several years and costing billions of dollars.

The following is a brief overview of the drug development process of small molecule drugs:

1.   Target Discovery 

Target Discovery is the process of choosing the target, which can be a protein or biological molecule, the modulation of which will elicit the desired therapeutic effect. This step is not a part of drug development but is essential as it helps to identify therapeutic targets based on the disease being treated. 

2.   Screening and Lead Identification 

Once the research team understands the physiological role of the target, they can assess how modulating it will affect the disease state and begin searching for a chemical agent to achieve the desired outcome. This process is known as Screening and Lead Identification. 

For targets with little prior knowledge, researchers often use high throughput screening (HTS) by testing a large library of diverse compounds to find potential hits. 

When more is known about the target, such as its binding site, virtual screening techniques like structure-based or ligand-based screening are used to focus on compounds with higher binding potential. 

Once suitable compounds are identified, thorough preparations, including creating assays and determining test conditions, are performed to validate the screening results.

3.   Lead Expansion 

At this stage, researchers perform additional tests to verify the leads identified in the previous stage to explore chemically similar compounds. 

4.   Lead Optimization 

Once some promising candidates are identified through lead expansion, they are further refined and enhanced to improve their safety, efficacy, and pharmacokinetic properties via Lead Optimization. 

Finally, preclinical and clinical trials are conducted to evaluate the safety and efficacy of the new small molecule drug and assess safety, dosage, and effectiveness, respectively.

Criteria for Selecting a Small Molecule Drug Substance Partner 

Selecting the ‘right’ small molecule drugs substance partner is easier said than done. It requires a range of factors to consider including materials and resources, expertise, scale-up capabilities, and more.

With an immense pool of contract development and manufacturing organizations (CDMOs) to choose from, picking the best manufacturer for a particular drug substance can be challenging. Enlisted below are a few factors pharmaceutical companies can consider when deciding on CDMO for small-molecule drugs: 

Materials and Resources

The fundamental aspect of developing novel small-molecule drugs is access to regulatory starting materials (RSMs) and APIs. The right CDMOs should have proper supply chain in place for sourcing RSMs and APIs.

Expertise and Experience

Another factor to look out for is expertise and experience in developing and manufacturing small-molecule drugs. Ideally, the CDMO should have integrated in-house teams with expertise in research and development, analysis, manufacturing, engineering, cGMP, and regulatory compliance.

Scale-Up Capabilities

During clinical trials focused on targeted indications, only a small volume of newly developed drugs is needed. For commercial production, a larger volume is required, so the CDMO should have adequate scale-up capabilities.

Regulatory Compliance

Regulatory compliance is a basic criterion for selecting CDMOs. Pharmaceutical companies should ensure that the CDMO has a GMP-compliant and certified facility, along with ongoing inspection plans.

Geographical Proximity and Timing

A CDMO with in-house analytical and compliance services can offer added benefits by reducing the need to outsource certain aspects of the project, thus saving time and resources.

Technological Infrastructure

State-of-the-art facilities and equipment are yet another factor to be considered when outsourcing small-molecule drug substance development are essential. Advanced technologies can significantly enhance the efficiency and quality of drug development processes.

Operational Efficiency

Operational efficiency includes several aspects, such as validated processes for R&D, scale-up, and manufacturing Efficient operational practices ensure the timely delivery of consistent quality of the drug substances.

Project Management and Communication

Clear communication and effective project management are key to successful collaboration. A CDMO that excels in these areas can manage timelines, resources, and expectations effectively, leading to smoother project execution.

Financial Health

Evaluating the partner’s financial stability and investment in R&D is important. Financially stable CDMOs are more likely to sustain long-term projects and invest in necessary innovations and improvements.

Conclusion

Choosing a small molecule drug substance partner can be a daunting task. However, with the majority of pharmaceutical drugs falling within this category, it is safe to say there already are enough CDMOs to collaborate with other companies for outsourcing. If your company is considering contract manufacturing for your products, consider the factors discussed in this article to ensure a successful partnership and smooth production process.

About the Author

Saher Haider

Saher Binte Haider is a pharmacy graduate from Dow University of Health Sciences. She started her career as a Quality Management professional in the pharmaceutical industry where she developed a keen interest in good documentation practices, SOP creation, and content writing. She has 7+ years of experience in healthcare & life sciences content writing. Her key areas of expertise are healthcare, pharmaceuticals, health tech, and AI in healthcare.