Biologically derived ingredients offer a whole host of possibilities for drug development. Sourced from living organisms, like plants, animals, or microorganisms, they possess inherent therapeutic properties – and some have been utilized for centuries in traditional medicine. However, tapping into the benefits of these ingredients is not always straightforward, owing to their intricate structures, supply chain complexities, and quality assurance challenges.
In this article, Bioiberica’s Head of R&D Human and Animal Health, Daniel Martínez-Puig, explores how drug developers can master the art of formulation with biologically derived ingredients to continue harnessing their unique potential, and ultimately support patients worldwide with innovative medicines.
Tapping Into the Power of Biologically Derived Ingredients
They come from natural origins, containing bioactive compounds with specific pharmacological effects that have been instrumental to medical progress throughout history for their use in the treatment of numerous medical conditions.
Take heparin as an example. Discovered in 1916, heparin stands as a testament to the transformative potential of biological compounds sourced from animals. Heparin is a widely used anticoagulant therapy that helps to prevent the formation of clots in blood vessels – and is estimated to save more than 100 million lives annually. It is primarily derived from animals, like pigs and cows, because it is naturally synthesized in the mast cells of these creatures – produced as part of their natural defense mechanism against injury or infection. The complex structure of heparin also makes it challenging to replicate synthetically. What is more, animal-sourced heparin has a unique spectrum of biological activities supported by robust scientific evidence, which is why the animal-derived molecule remains the most commonly used form in clinical settings worldwide.
Other standout examples of biologically derived ingredients used in the pharmaceutical industry are chondroitin sulfate- and glucosamine-based medicines which target osteoarthritis in older individuals, and drugs based on thyroid – also known as natural desiccated thyroid (NDT) – used for the management of hypothyroidism.
Navigating Formulation with Biologically Derived Ingredients
Despite their undeniable therapeutic potential, formulating with biologically derived ingredients – especially animal-origin compounds – poses unique challenges. Due to their complex structures and properties, it can be more difficult to achieve consistency, stability, and optimum bioavailability of the final drug product for instance.
But it is not just the drug formulation itself that is complex. These ingredients come with a plethora of other challenges linked to traceability and quality control issues, supply stability, and also sustainability and ethical concerns. Addressing these issues is critical for ensuring the development of safe and effective pharmaceutical solutions.
So, what are some of the key considerations when incorporating a biologically derived ingredient into drug formulation approaches? What are some strategies for success? And what criteria should manufacturers consider when choosing an ingredient partner to give them the utmost confidence?
1. Traceability and quality control
It is critical for drug formulators to be able to trace biologically derived ingredients back to their original source to maintain maximum quality control – and ultimately the safety of their pharmaceuticals. Any variation in the source material can impact the consistency and efficacy of the final product.
In the realm of animal-derived ingredients, this is viewed as especially important. Adopting quality assurance and traceability technologies that support rigorous monitoring and control of the entire supply chain, from raw material sourcing to final product distribution, will help to provide confidence in the safety, purity, and authenticity of animal-derived ingredients.
A vertically integrated supply chain can also provide greater control over raw materials, intermediates, and finished products. Here is why:
- This supply chain model enables seamless traceability of materials and products throughout the manufacturing process, allowing companies to track the origin of ingredients, monitor production processes, and quickly identify and address any issues or deviations.
- Internalizing key manufacturing processes or sourcing critical raw materials reduces reliance on third-party vendors, safeguarding against quality issues.
- By integrating multiple stages of the supply chain, it is easier to optimize production processes, reduce waste and eliminate inefficiencies.
- Vertically integrated supply chains also offer greater flexibility and agility in responding to changes in market demand or supply chain disruptions, meaning businesses can quickly adjust production volumes, modify product specifications, or switch suppliers as needed.
Considering this, for drug companies seeking a supplier for biological ingredients, one that operates via a vertically integrated supply chain offers a significant edge.
2. Analytical testing and expertise
Unlike ingredients obtained from chemical synthesis, biologically derived ingredients are inherently susceptible to high variability due to their natural origin.
Having the analytical knowledge and validated analytical methods to support the full characterization of biological ingredients in various formulations is therefore critical to meeting quality and safety standards, and ensuring formulations featuring these compounds are compliant with the latest regulations. In the case of chondroitin sulfate, for instance, its biological effects can differ substantially depending on its purity in the final dosage form. While some formulations demonstrate anti-inflammatory effects, others exhibit weaker effects, and in some instances, can even be pro-inflammatory.1 This highlights the importance of ingredient characterization and analysis to support end-product quality and efficacy.
3. Resilient supply chains
While synthetic ingredients can be produced consistently in a lab setting, because biologically derived molecules are not, they are subject to a higher risk of supply fluctuations. The reason for this is that, generally, large volumes of starting material are needed to obtain biologically derived ingredients. However, the raw material used to extract or produce the target molecule can be significantly affected by factors like climate, natural disasters, disease outbreaks, or environmental changes. Any disruptions can impact production schedules supply chain stability, and ultimately patient access to critical medications. So, how can manufacturers limit their vulnerability to (sometimes) unavoidable supply disturbances and side-step disruptions to production?
Conducting comprehensive risk assessments and developing contingency plans can help to identify potential vulnerabilities and mitigate (most) risks. Proactively monitoring raw material availability, geopolitical risks, regulatory changes, and environmental factors, for example, can help drug developers anticipate and address disruptions. Choosing a reliable ingredient partner also has a big part to play though. Collaborating with a supplier that has diverse sources of biologically derived ingredients reduces reliance on one single source. In the case of animal-origin ingredients, for instance, it is better to use a partner that sources from different countries globally, rather than depending on the livestock population in a specific region of the world.
4. Overcoming contamination concerns
Contamination and safety concerns can be a significant concern for formulators using animal-origin active ingredients. That is because, despite the widespread use of animal-derived ingredients, like heparin, they do carry a risk for potential contamination with impurities, infectious agents (like pathogens), or allergens. To address this, at Bioiberica we ensure the safety of our partners’ pharmaceutical products and mitigate risks to public health, by implementing rigorous testing, purification processes, and comprehensive risk assessment protocols in place.
5. Roots in sustainability
Sustainability is becoming a key focus for the healthcare and pharmaceutical industries – fueled by growing environmental concerns, regulatory pressures, and economic incentives. Arguably, the utilization of biologically derived components necessitates an even greater commitment to sustainability, being extracted from natural resources. However, there is a prevailing belief that certain biologically derived compounds, particularly those obtained from animal sources, lack sustainable credentials altogether.
The careful selection of an ingredient partner that respects the health of the planet and has robust sustainability initiatives in place will help pharmaceutical companies prioritize patient outcomes while minimizing environmental harm. In the case of biologically derived active ingredients, sustainable sourcing practices, waste reduction, and ethical treatment of animals – including sourcing from certified farms and compliance with animal welfare standards – are key considerations when selecting a supplier. At Bioiberica, one of the ways we tackle this is by operating via a circular economy model. This is a meticulously designed production system, which helps to minimize water consumption, energy usage, and the utilization of auxiliary raw materials.
Concluding Thoughts
Biologically derived ingredients have the potential to transform patient care. However, navigating the formulation of these compounds can be complex. To give drug developers the ultimate confidence in using biologically derived ingredients, it is important to embrace collaboration – and choosing the right ingredient supplier is central to this.
References
- Martel-Pelletier J, Farran A, Montell E, Vergés J, Pelletier JP. Discrepancies in composition and biological effects of different formulations of chondroitin sulfate. Molecules. 2015 Mar 6;20(3):4277-89. doi: 10.3390/molecules20034277. PMID: 25756648; PMCID: PMC6272499.
Author Details
Daniel Martínez-Puig, Head of R&D Human and Animal Health- Bioiberica
Publication Details
This article appeared in American Pharmaceutical Review: Vol. 27, No. 4 May/June 2024Pages: 56-58
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