Pharmaceutical Manufacturing Processes: An Overview

The pharmaceutical industry is among the largest industries in the world with an expected compound annual growth rate (CAGR) of 5.9% between 2024 and 2031. The growth of this industry depends heavily on developing new medications and products. A huge part of this growth is attributed to pharmaceutical manufacturing processes.

It is necessary to understand pharmaceutical manufacturing processes to ensure drug safety and efficacy, ensure compliance with regulatory standards, foster innovation within the company, effectively manage crises, and fulfil ethical responsibilities. People working in the pharmaceutical industry, both directly and indirectly, should especially understand pharmaceutical manufacturing processes.

This article highlights the three most common pharmaceutical manufacturing processes: chemical synthesis, fermentation, and bioprocessing.

Chemical Synthesis

Chemical synthesis is one of the most important pharmaceutical manufacturing processes because it involves the creation of complex compounds from basic materials. These complex compounds are used to synthesize the drug formulation.

Importance of chemical synthesis

Chemical synthesis is important for any pharmaceutical company because:

• Affords APIs: Chemical synthesis processes are used to synthesize active pharmaceutical ingredients (APIs). These APIs are the core of any medication as they carry the ingredients that will have the desired treatment effect on the individual.
• Allows scalability and consistency: Without a proper chemical synthesis process, it is difficult to prepare large batches of drugs, which is often required by all pharmaceutical companies. Chemical synthesis processes allow pharmaceutical companies to accurately synthesize multiple batches of products. Furthermore, because synthesis protocols are pre-defined during the research and development stage, they also ensure batch-to-batch consistency of the product.
• Improves cost efficiency: Developing efficient chemical synthesis processes ensures companies can use their resources to the fullest extent. This ensures low product loss, high yield, and low byproduct formation, which decreases the total cost of production.

How are chemical synthesis processes developed?

• Route selection: It is necessary to choose the synthesis route with the highest production efficiency. This may not be the quickest process.
• Feasibility study: After selecting the process, feasibility studies should be performed to determine the scalability of the route and whether the process meets the necessary production requirements.
• Procurement: If the process passes the feasibility study, appropriate reaction apparatus such as instruments, materials, and catalysts should be purchased.
• Laboratory setup: In most cases, synthesis processes are a combination of multiple reactions such as fabrication, isolation, and purification. Hence, the laboratory setup should be such that these reactions do not interfere with each other, and workers can swiftly initiate the next reaction after the first ends.
• Optimisation: The reaction conditions need to be adjusted to obtain maximum yield. The products should be characterised to ensure they have the best quality. If not, reaction conditions should be further optimised.
• Production: Once the necessary parameters are optimised, batch-scale reactions can be performed for large-scale synthesis.

Fermentation

Fermentation is a biochemical process in which microorganisms such as yeast, fungi or bacteria are used to convert compounds into desired products.

Importance of fermentation

• Antibiotic production: Fermentation processes are used to manufacture various antibiotics such as erythromycin and tetracycline.
• Vaccine manufacturing: Fermentation is an important step in the manufacturing of vaccines. Microbial fermentation systems are used to produce vaccines such as hepatitis B vaccine.
• Production of other building blocks: Common building blocks used in drug development are often synthesized via fermentation. For example, proteins, amino acids, vitamins, hormones, enzymes, and probiotics are produced via fermentation processes.

How are fermentation processes developed?

• Culturing: A small quantity of microorganisms (bacteria, yeast or fungi) are grown under controlled conditions.
• Scaling-up: This small quantity is then scaled up to prepare inoculum.
• Procurement and laboratory setup: Fermentation processes are usually performed in bioreactors or fermenters. Therefore, these instruments along with all materials, microorganisms, catalysts, and enzymes, need to be purchased and set up in the laboratory.
• Fermenting: Once the lab is set up, the fermentation process is performed according to pre-decided guidelines. During the process, microorganisms metabolize the substrate to afford the product.
• Optimization: The fermentation conditions like temperature, volume, and humidity need to be optimized to ensure the highest yield.
• Additional processing: Some products may require additional processing to remove byproducts, denatured enzymes, microorganisms.

Bioprocessing

Bioprocessing uses biological materials to produce pharmaceutical products such as medicines. Bioprocessing encompasses many pharmaceutical manufacturing processes. However, for the purpose of this article, we will discuss bioprocessing as a whole.

Importance of bioprocessing

• Complex therapies: Bioprocessing is required to obtain complex biological materials which cannot be synthesized via chemical reactions. For example, monoclonal antibodies and nucleic acid-based drugs cannot be synthesized via chemical reactions.
• Advanced therapies: Bioprocessing can be used to develop advanced therapies to treat genetic mutations and disorders such as cancer. Cell therapies and gene therapies are advanced options that cannot be realized via the chemical or physical route.

How are bioprocessing processes developed?

The steps of bioprocessing are very similar to those of fermentation because fermentation is a type of bioprocessing. However, some steps are different and more important.

• Cell lines: In most bioprocessing procedures, cell lines are used. Therefore, appropriate cell lines need to be selected and prepped for the experiments. Furthermore, cell lines also need to be optimized to realize better scalability, stability and efficiency.
• Upstream processing: This usually involves prepping the cell lines or microorganisms for the process and preparing the culture media.
• Downstream processing: This is usually performed after the cells or organisms have been cured in the necessary media and have undergone necessary reactions. In this step, cells are harvested, purified, and analyzed.
• Regulatory compliance: There are strict regulatory guidelines where bioprocessing is concerned. Furthermore, companies also have to adhere to ethical guidelines when using mouse, animal and human models.

Conclusion

Chemical synthesis, fermentation, and bioprocessing are only three examples of pharmaceutical manufacturing processes. However, these are the three most widely used processes, and most pharmaceutical companies use at least one of the three.

This article has highlighted the definition, importance and steps of each pharmaceutical manufacturing process. However, one key thing to remember is that before engaging in any of the three practices, thorough study and understanding are required. This article provides only a brief idea; before starting any of the three processes, remember to learn more about these processes, especially their regulatory guidelines and compliance requirements.

FAQs

1. Which is the most important pharmaceutical manufacturing process?

It is difficult to quantify the importance of a pharmaceutical manufacturing process in the industry because each process plays a different role and affords a different product. In most pharmaceutical companies, manufacturing processes are a combination of multiple mini-processes such as synthesis, isolation, purification, characterization, etc.

2. What are some common challenges in pharmaceutical manufacturing processes?

Regulatory compliance and quality control are common challenges for most companies. Companies have to regularly review their manufacturing processes to ensure they are compliant and afford high-purity products.

3. How are manufacturing processes divided?

Pharmaceutical manufacturing processes are divided into batch processing (products are synthesised in batches) and continuous processing (products are synthesised using a continuous never-ending process).