How Organic Synthesis is Accelerating Drug Discovery in Pharma

In an interaction with India Pharma Outlook, Ajay Bhardwaj, CEO, Anthem Biosciences Private Limited discusses about the role of organic synthesis in accelerating drug discovery, highlighted the significance of diligence at an early stage, AI-driven innovations, and green methodologies strategies. With over three decades of experience in the pharmaceutical and biotechnology sectors, he has played a key role in advancing life sciences, contract research and clinical research.

How can companies streamline organic synthesis process to speed up drug discovery and reduce development costs?

The success of drug discovery depends on the quality of target selection and the identification of potential drug candidates. While identifying a potential candidate, the level of diligence has gone into that, decides the quality of candidate. Then it will be less iteration required to get to a drug, possible drug candidate.  However, nowadays there is a significant emphasis on AI, and there are new packages, and new tools being developed, which will speed up drug discovery. People are quite enthused about the emergence of AI in drug discovery.

What effective methodologies can businesses adapt to enhance the efficiency of early-stage organic synthesis and speed up drug development?

Modifying a compound later can be inefficient and costly, which is why the initial selection of a drug candidate is so crucial. The amount of diligence applied during this phase has direct effects on the success of drug development. In some cases, lots of work was done only to find out that the compound was poorly soluble. Consequently, the whole process had to be re-done, resulting in lost time and money.

Solubility is a basic requirement—without it, efficacy testing is not practical, and the compound will not be successful as a drug. Basic but essential mistakes such as this can lead to major setbacks. Thus, it is necessary to establish the problem statement at an early stage so that all the required criteria are fulfilled. A well-organized checklist ought to contain important considerations like the desired route of administration (oral tablet, solution, or injectable), whether the medication is systemic or localized, and frequency of dosing (e.g., once a day for chronic therapy). Only after careful consideration of these factors should the synthesis of the organic compound be initiated. Any necessity to go back to drug development is a costly undertaking. Moreover, early-stage testing, including toxicity screening, should be given priority to prevent costly revisions down the line.

The first step in drug development involves carrying out in vitro tests and animal testing to assess toxicity, determine metabolites, and identify if any genotoxic material is formed during the process. Through early proactive evaluation of these elements, researchers can refine their strategy before going further in development, conserving considerable amounts of time and money.

How can companies simplify organic synthesis approaches for structurally complex drug molecules to reduce cost and shorten development timeline?

To minimize the drug development timeline, it is necessary to complete the required phases efficiently. Drug development is a highly regulated industry and preclinical work is followed by Phase 1, Phase 2, and Phase 3 clinical trials. As the process goes on, the costs are exponentially higher, and hence late-stage development is very costly. Efficiently managing costs and time is identifying issues early during the development stage. It takes care of fixing problems at an early stage before it causes rework at a later stage. This is where the experience and expertise of people like Anthem who are specialized in their field comes into play. Our expertise will ensure that the development takes place in a Good Manufacturing Practice (GMP) environment so that rework can be avoided.

Also, clinical study batches need to be manufactured in a certified facility with the required regulatory approvals. Since this information is so important to regulatory submissions, any failure to monitor could mean repeating expensive and time-consuming processes. A solidly planned and strictly followed early-stage development process minimizes risks significantly, and there is an easier transition through subsequent stages without unnecessary delays or costs.

This is also very time-consuming and expensive. In order to reduce development times, one method is to seek out alternatives to traditional organic and small-molecule medicines. Biologics, providing more targeted therapies, can be a very effective choice. However, creating biologics needs an entirely different set of skills than that required for small-molecule drug development.

Such players as Anthem, with experience in both biological and small-molecule development, are crucial in this area. It is very important to identify whether the drug candidate will be a large molecule (fermentation-based biologic) or a small molecule. This has major implications for the development strategy, regulatory needs, and overall project duration. Determining the optimal approach upfront provides a more efficient and cost-saving drug development process.

How can businesses adapt sustainable organic synthesis practices without compromising on speed, cost, or profitability?

It is a misconception that adopting green methodologies results in additional costs. If it is properly implemented, it can generate substantial cost savings. Our company is a good example of such a practice, having one of the lowest ESG ratings among our peers due to our commitment to sustainability, which also enhances cost efficiency. For example, take the processes of fermentation. A complicated big molecule can be produced using multi-step organic synthesis, which involves time and costs. Instead, fermentation can obtain the same result more economically by using microorganisms to naturally execute the process. This method reduces time and cost and also aligns with sustainable practices.

Another cost-saving and sustainable method is embracing continuous manufacturing rather than traditional batch processing. While increasing batch sizes is a common strategy to reduce costs, continuous manufacturing optimizes production efficiency by maintaining a steady process flow, which results in additional cost savings and enhanced sustainability.

What approaches can companies take to ensure efficient and cost-effective scale-up of organic synthesis for commercial technical production?

In laboratory-scale research, the objective of a researcher is to get the product done. Researchers focus on speed rather than economics, they need speed to be able to manufacture enough material so that they can do screening against appropriate drug targets. So that is a different approach. This approach differs significantly from the scale-up process. When scaling up, several critical factors must be addressed early on. One key consideration is economics—ensuring cost-effective production. Another is hazard assessment, which involves evaluating potential risks in manufacturing, such as safety concerns for both the plant and its workers. This level of study takes place after the R&D phase and requires specialized expertise and that's what Contract Development and Manufacturing Organizations (CDMOs) such as Anthem offer.

We have the expertise to assess a process to ensure that, once scaled up, it remains economical, viable, and efficient. It is essential to avoid reliance on raw materials from regions prone to conflict, as this could disrupt production. These considerations play a significant role in the scale-up process. So the best thing is that scale-up should be left to people who are experts in scale-up, and lab work is left to scientists or bench chemists who are good at doing that. So it requires different skills, and the best way to do it is to entrust it to people who have scale-up experience.

How can companies improve the organic synthesis purification process to meet regulatory standards faster and at a lower cost?

During purification, people will do a common chromatography approach. However, not every purification process requires that. People who are experts at scale-up often emphasize that columns are very expensive to do any column chromatography. However, a crystallization technique will save so much cost, money, and speed. Chromatography can be time-consuming, sometimes taking days to complete a single step due to the loading and processing involved.

Scale-up is a different challenge and minimizing costs at this stage requires strategic techniques—crystallization being one such effective approach. In a laboratory setting, you may be isolating components at each step. Rather than isolating a component at every stage, it is often more efficient to proceed directly to the next step. This approach minimizes material loss and saves time, as unnecessary purification between stages can lead to both inefficiencies. Also, there are various techniques available to optimize this process.

It is not a straightforward, one-line answer, but to employ modern manufacturing techniques with greater instrumentation and control is essential. Additionally, in our industry, maintaining data integrity is a critical requirement. During development, it is important to ensure that the process stands up to regulation and scrutiny. Considering these factors early in the drug development process is vital, as it saves both time and costs.

Organic synthesis and drug discovery have been around for a long time. However in today's digital world, particularly with advancements in AI, the focus is on optimizing processes to reduce the number of steps in a shorter timeframe. For example, if a screening algorithm screens a million compounds and comes up with a short list of a thousand, AI can make it in a more sophisticated way by further refining the selection to just ten highly probable candidates. Instead of analyzing a thousand compounds, you only need to focus on ten, significantly reducing the time and effort required compared to starting with a vast pool of compounds. This is the advancement made possible by modern AI and machine learning.