April 12, 2024

Active Pharmaceutical Ingredients – The Core of Drug Formulation

Active pharmaceutical ingredients, commonly known as APIs, form the core component of any drug or medication. These ingredients are responsible for the intended pharmacological activity of a drug when administered to patients. In this article, we will discuss in detail what APIs are, their significance in the pharmaceutical industry and key aspects related to their production, quality control and regulations.

What are APIs?

APIs, sometimes also called drug substances, are any substances or mixtures of substances that are used in a finished pharmaceutical product and that, when administered to a patient, possess the intended pharmacological activity to diagnose, cure, treat or prevent disease. APIs may be obtained through synthesis, semi-synthesis or isolation from biological sources. Common examples include paracetamol, ibuprofen, amoxicillin, azithromycin and omeprazole which are active moieties in many analgesic, antibiotic and antiulcer drugs.

Production and Quality Control of APIs

Given their critical role in ensuring drug efficacy and safety, APIs require stringent production methods and quality checks. They are mainly manufactured through specialized chemical or biological processes in dedicated facilities which need to meet current Good Manufacturing Practices. Quality parameters like identity, purity, strength and stability are rigorously tested during and post-production using advanced analytical techniques like chromatography and spectroscopy. Even minor impurities can negatively impact the therapeutic properties or increase toxicity of drugs. Hence, quality control of APIs is of utmost importance.

Dependence on API Imports

A large proportion of APIs consumed by the pharmaceutical industry globally are imported, primarily from China and India which have emerged as major API manufacturing hubs. As per estimates, around 70% of the global API supply comes from China alone. This heavy reliance on imports poses risks to drug security in case of supply chain disruptions or trade restrictions. It also raises quality concerns due to inconsistencies in manufacturing standards across geographies. Hence, self-sufficiency in APIs has become a strategic priority for many countries.

Role in Drug Development and Approvals

A drug cannot enter clinical trials or receive regulatory approval without characterization and validation of its API. Comprehensive documentation covering API properties, synthesis methods, intermediate purification etc. forms an integral part of Investigational New Drug applications and New Drug Applications reviewed by health agencies like US FDA. Variations to approved API specifications also require prior regulatory consent. This approval process helps ensure consistent drug quality and performance in patients.

Intellectual Property Rights

Given the knowledge, R&D and investment required, APIs developed via new chemical entities often enjoy patent protection for a fixed period. Patents grant exclusive marketing rights to innovator companies and prevent generic competition until expiration. However, patents on APIs may also give rise to legal disputes between innovators and generic drug manufacturers exploring ways to circumvent intellectual property. This remains a contentious issue with implications on drug accessibility and affordability.

Regulation of APIs

To guarantee API quality, national and international regulatory bodies have instituted stringent rules and guidelines that govern API manufacturing, testing, import/export and change control. The International Council on Harmonisation (ICH) aims to harmonize technical requirements through consensus between regulatory authorities in different geographies. Other key regulations include US FDA’s cGMP guidelines, API Master File procedure and EU directives covering API manufacturers, importers and distributors. Violating any of these norms can result in penalties, import bans or withdrawal of drug approvals.

Role of Excipients

While APIs deliver the intended pharmacological effects, excipients aid drug formulation by facilitating various processes like diluting, coating or binding the active substance and determining properties like ease of administration and stability. Common pharmaceutical excipients include binders, preservatives, flavors, colors, lubricants and disintegrants. Their appropriate selection and concentration is vital for optimal drug performance and safety. Excipients are also governed by national and international standards and guidelines.

Biosimilars and Generic APIs

With patent expiries of blockbuster biologics, biosimilar versions emulating reference biologic APIs are gaining traction globally due to their comparable quality and lower costs. Similarly, off-patent chemical drug APIs are now manufactured generically by multiple players after undergoing required bioequivalence testing overseen by regulators, greatly expanding treatment access. However, developing and establishing equivalence of complex biologic or generic APIs remains a major technological and regulatory challenge.

New Trends

Emerging areas like personalized medicine, 3D drug printing and nanomedicines are opening up novel opportunities for engineering APIs with tailored properties like targeted delivery and controlled/sustained release. Advancements in recombinant DNA technology, genomics, drug metabolism studies and process analytical technologies are also driving continued innovation in API synthesis, analysis and production mechanisms industry-wide. These trends promise to revolutionize disease management, improve treatment effectiveness and expand the API landscape beyond traditional boundaries.

Closing Remarks

To summarize, APIs form the foundation of modern pharmacotherapy. Their development, regulation and quality control requires extensive scientific understanding and infrastructure investment. While APIs will remain indispensable as drug backbones, new delivery approaches are expanding their applications. Continued innovations in API design and manufacturing aligned with evolving regulatory frameworks hold the key to addressing unmet medical needs sustainably and affordably.

1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it