Biologics: Science behind modern medicine

The programme envisions transforming India into a global biomanufacturing hub through strengthened research programmes by establishing three new National Institutes for Pharmaceuticals Education and Research (NIPERs). It also seeks to strengthen the existing infrastructure, and create a network of 1,000 accredited clinical trial sites. 

Hence, the programme signals a shift towards strengthening domestic production of biologics and biosimilars with the already existing strength in small molecule production. 

Also, in January 2026, Biologics X 3DCC Summit –  a landmark unified summit that merges two of India’s most influential scientific conferences: the 6th Annual Summit on Biopharmaceutical Product Development (Biologics 2026: Emerging Frontiers) and the 3rd Edition of the International Conference on Advances in 3D Cell Culture (3DCC 2026) – was held.

The initiative aimed to bring together stakeholders to promote collaboration and accelerate the translation of affordable therapies from bench to bedside. It also highlighted recent advances in 3D cell culture for developing monoclonal antibodies, cell and gene therapies, and other next-generation biotherapeutics. 

However, the question remains: What makes such technologies possible in the first place? How do biologics, ranging from fertility treatment to vaccines and RNA platforms, differ from conventional drugs? 

What are biologics?

Modern medicine is dependent on two broad categories of therapeutics:

1) Chemically synthesised drugs – It includes drugs like paracetamol (an antipyretic) and amlodipine (used to control blood pressure), whose chemical structures are known and well characterised.

2) Biologics – Like blood, plasma, monoclonal antibodies, and insulin. Biologics are generally obtained as complex mixtures, and are not easily identified or completely characterised. 

They are generally derived directly from natural sources like microorganisms, animals and humans (e.g., blood, platelets), or through cutting edge biotechnological procedures (cell free synthesis).  

Crucially, the rapidly evolving field of biotechnology has made the biotech industry highly dynamic with frequent innovations and short product life cycles. And biologics now encompass a wide range of therapeutic solutions from IVF to vaccines. 

Modern in vitro fertilisation 

With advances in therapeutics and rising incomes, the demand for biologics has increased significantly. For instance, many middle-income couples now choose delayed pregnancy. In such cases, the Anti-Müllerian Hormone (AMH) test is widely used in reproductive medicine because it helps assess ovarian reserve.

Compared to earlier tests determining the ratio of follicle-stimulating hormone to luteinizing hormone (FSH/LH), AMH level is considered a more reliable indicator of fertility potential.

Consequently, modern in vitro fertilisation (IVF) treatments rely heavily on accurate AMH testing. These tests typically use mouse monoclonal antibodies produced in hybridoma cell lines. These antibodies are highly specific antibodies produced by identical immune cells derived from a single parent cell.

Maternal age strongly influences pregnancy outcomes, as advanced age increases the risk of conditions such as Down syndrome in newborns, while early first pregnancy is protective against certain cancers. Nevertheless, IVF treatments continue to be widely marketed.

But IVF has limited success rates (around 17 per cent per cycle) compared with natural conception (around 31 per cent), partly due to the artificial environment of fertilisation. Alternative approaches, such as gamete intrafallopian transfer (GIFT), use superovulation drugs produced in Chinese hamster ovary (CHO) cell lines.

Vaccine technologies

Vaccine technologies range from inactivated viruses to nucleic acid–based platforms such as RNA vaccines and viral vector vaccines (e.g., adenovirus-based platforms like Covishield).

CRISPR-based genome editing therapies are also advancing rapidly in the field of genomic medicines. As of 2025, however, monoclonal antibodies (mAbs) remain the largest segment of products, accounting for 54.2 per cent of the biologics market. 

Challenges in therapeutic biologics

However, therapeutic biologics face many challenges involving the production, purification, administration, detection, quantification, and targeting of proteins of interest (POIs) among thousands of background proteins. 

Earlier, researchers purified only microgram to milligram quantities of proteins from kilograms of  animal tissue, often obtained from slaughterhouse waste. However, this approach has two major limitations:

First, protein distribution in cells is highly skewed. For example, about 97 per cent of protein in human red blood cells is haemoglobin, while thousands of other proteins constitute only about 3 per cent. 

Second, even with extensive purification and quality control, contaminant proteins often remain. This is particularly concerning during therapeutic administration, as proteinaceous infectious agents (prions) such as those causing diseases of the nervous system (like mad cow disease, kuru, and scrapie) pose serious risks. In addition, contaminating viral nucleic acids requires extensive safety testing.

How advances in cloning technology address challenges

Major advances in cloning technology have addressed many challenges in protein production. Because genes are modular, a gene from one organism can be expressed in another unrelated host with minor modifications. 

For example, human genes can be cloned into simple unicellular bacteria to produce proteins, which are then extracted and purified after cell lysis. This approach poses minimal ethical concerns and low risk when non-pathogenic bacteria are used. 

However, biologically active proteins – particularly larger ones – often require complex folding mechanisms and specialised cellular machinery that can vary between organisms. Proteins can also contain an additional layer of structural information beyond the amino acid sequence known as glycosylation (addition of sugar molecules to proteins). AMH is a glycosylated peptide. 

Why therapeutic proteins are produced in mammalian cells

In some cases, protein function and recognition depend not only on the amino acid code but also on specific sugar modifications, which simple bacteria cannot produce. While some glycosylation patterns are conserved from yeast to humans, others vary between organisms. 

Therefore, such therapeutic proteins are produced in mammalian cells like Chinese Hamster Ovary (CHO) cell lines. In these systems, extrachromosomal plasmid DNA is introduced into CHO cells, which gets integrated into the genome through random or cite-specific integration. The gene dose and protein production can be controlled by varying the concentration of suitable selection marker (mostly an antibiotic added to the culture). 

However, integration of foreign DNA can result in genetic instability of host cells. Clones are sometimes lost or can accumulate sub-variants in a subpopulation of clonal cell lines. It affects purity, titre, and quality of the final product. Also, spontaneous mutations can accumulate and further affect the final product. 

Decoding biomanufacturing: cells, systems, and scale-up

These challenges are particularly important because a large spectrum of current vaccines is usually manufactured using cell-based expression systems, such as mammalian and insect cell lines, as well as bacterial or yeast cultures. 

Recently, plant molecular farming has been used for the production of seasonal influenza vaccines. It is envisaged to play a unique role in low-resource areas in the development of niche and orphan vaccines, and in the production of virus like particles (VLPs).

Molecular engineering is followed by process scale-up in bioreactors, which convert low-value inputs into high-value biological products. Key determinants of biological production are temperature, pH, dissolved oxygen, cell density, and growth media composition. In bioreactors, these variables are monitored and controlled through oxygen transfer, mixing, and flow rates to optimize product formation. 

Since different cells vary in size and structural properties, shear forces must also be regulated. Thus, stirred tank reactors are suitable for robust microbial cells, while gentle bag reactors are ideal for mammalian cells. Advances in sensors and process analytics now enable precise monitoring and balancing of bioreactor input and output fluxes.

Current trends emphasise continuous production, single-use bioreactors, and cell-free synthesis, supported by automation and AI-driven process monitoring to improve manufacturing and scalability. 

Ethical and economic concerns

Despite rapid advances in biotechnology, important ethical and economic concerns are emerging. Many innovations are developed using publicly funded research, yet their commercialisation often limits access for those who cannot afford them. 

Early biotechnology research investments were largely venture-driven, with profits frequently reinvested into scientific research. But as breakthrough achievements become increasingly difficult, investors may choose safer options. Such options may be less relevant to the current priorities of societies, and primarily cater to only a few. 

For example, the current flow of funds in ageing research outpaces the funding required for neglected tropical diseases like Leishmania, Schistosomiasis, and even enteric diseases like cholera and diarrhoea that still cause a large number of fatalities in poor countries. 

Post read questions

What are biologics? How do they differ from small-molecule drugs in terms of structure, production, and regulation? Illustrate with suitable examples.

Discuss India’s potential to become a global biomanufacturing hub. Evaluate the role of initiatives such as Biopharma SHAKTI.

What are the challenges faced by India in scaling advanced biologics such as cell and gene therapies?

Why are biologics more complex to produce than conventional drugs? Discuss with reference to glycosylation and cell-based expression systems.

Discuss the intersection of biotechnology, ethics, and reproductive rights in India.

(Dr. Arunangshu Das is the Principal Project Scientist at the Centre for Atmospheric Sciences, Indian Institute of Technology, Delhi.)

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