May 21, 2024

Navigating the Landscape of Biologics: Manufacturing, Mechanisms, and Regulatory Considerations

What are Biologics?

A biologic medicine refers to any medicine made from living organisms or contains components of living organisms. Biologic medicines, also known as biologics or biological products, are generally large, complex molecules manufactured or extracted from biological sources. These medicines are used to treat a variety of diseases, including cancer, autoimmune disorders, and infectious diseases. Common examples of biologics include vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins.

Types of Biologics

Biologics are typically categorized into seven broad categories:

Vaccines – Vaccines provide active acquired immunity to a particular disease. Examples include vaccines for hepatitis, measles, human papillomavirus (HPV), and influenza.

Blood Components – Whole blood and its components, such as red blood cells, platelets, and plasma, are used for treating a variety of medical conditions that require replacement of blood and blood clotting factors.

Allergenics – Allergenics aim to treat or prevent allergic diseases by modifying the patient’s immune response. Examples include allergen immunotherapy vaccines for allergic rhinitis, asthma, and insect sting allergies.

Somatic Cells and Tissues – Somatic cell and gene therapies utilize living human cells or permanent cell lines to treat disease. Examples include cartilage repair therapies and skin substitutes for wound healing.

Gene Therapies – Gene therapies deliver genetic material into patient cells for therapeutic benefits. They are a promising approach for treating inherited disorders, some types of cancer, and certain viral infections.

Recombinant Proteins – Recombinant proteins are produced from living cells that have undergone genetic modification to express a specific protein. They include important biologics for treating diabetes, cancer, and blood disorders.

Cellular and Tissue-Based Products – This category includes therapies derived from human cells and tissues, such as bone, ligaments, skin, and corneas, which may undergo processing but do not involve recombinant technology.

Manufacturing of Biologics

Given their complexity and sensitivity to manufacturing processes, the development of biologics requires advanced and highly-controlled manufacturing technologies:

Living Cell Cultures – Most biologics are manufactured using cells from animals or microorganisms that have been genetically engineered to express the therapeutic protein. Quality cell banks are created and scaled up under sterile conditions in bioreactors.

Purification and Formulation – Purification involves selective separation techniques like chromatography to isolate the target protein from other cellular components. The purified product is then formulated into a solution suited for delivery and long-term stability.

Quality Testing – Rigorous testing verifies product identity, strength, potency, purity, and safety according to regulatory standards. This includes tests for characteristics, contaminants, toxicity, and potency.

Fill and Finish – The purified and tested product is aseptically filled into containers, labeled, and packaged for distribution and administration. Quality testing continues during long-term storage and stability monitoring.

Regulation of Biologics

Due to their complex nature and potential safety concerns, the development and manufacturing of  Biologics are highly regulated. In the United States, the FDA regulates biologics through the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER). Key aspects of oversight include:

Preclinical Testing – Extensive nonclinical and preclinical testing is required to demonstrate safety and efficacy in relevant animal models prior to human clinical trials.

Clinical Trials – Clinical trials involve testing in humans through phases I-III to collect additional data on quality, safety, and efficacy.

Product Approval – A Biologics License Application (BLA) or New Drug Application (NDA) provides evidence to support that the biologic product is safe, pure, and potent for its intended use.

Post-Approval Monitoring – Continued safety surveillance and periodic reporting are required even after approval. Manufacturers must make and record all production and control changes according to their biologics license.

Challenges with Biologics

While biologics have great promise as advanced treatments for many serious conditions, their development and use also presents some unique challenges compared to conventional small molecule drugs:

Complex Nature – Biologics are complex macromolecules derived from living systems, and understanding their structure-function relationships is not always straightforward. Even minor changes during manufacturing could impact safety or efficacy.

Manufacturing Precision – The reproducible and highly-controlled manufacturing processes required for biologics adds significantly to production costs compared to conventional drugs. Manufacturing issues can potentially disrupt product availability and supply chains.

Immunogenicity – As biological molecules foreign to the human body, biologics may potentially induce an immune response or antidrug antibodies that reduce their effectiveness or cause adverse reactions over time.

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