In the world of pharmaceuticals, the drug substance manufacturing process is a critical component in bringing life-saving medicines to patients. This complex process involves several steps, adherence to stringent rules, and upholding the highest standards of quality.
This process is based on the basic Good Manufacturing Practice (GMP) principles i.e. SISPQ; which means a drug substance / drug product should be manufactured in such a way, that achieve Safety, Identity, Strength, Purity and Quality.
In this article, we will go through with the various phases from drug development through the ultimate delivery of the active pharmaceutical ingredient (API), taking a close look at the manufacturing process of drug substances/ drug product.
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| Figure: 01: Pharmaceutical Drug Substance Manufacturing Flow: From Discovery to Delivery |
1. Drug Discovery
The process of producing drug substances starts with drug discovery, in which pharmaceutical companies look into and find prospective new chemicals entity (NCE) that might be used to treat particular medical conditions.
To find the most promising options with the needed therapeutic effects, scientists carefully examine thousands of chemicals. An identified lead compound is put through extensive testing to determine its safety and effectiveness.
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| Figure: 02: Drug Discovery |
2. Preclinical Research
As a result of drug discovery, once the lead compound is identified, preclinical research starts. This stage involves a deep dive study performed on cell-cultures and animal models to evaluate the compound's pharmacological characteristics, toxicity, and potential side effects.
The objective of this stage is to collect the crucial data and vital information to assist the "Investigational New Drug (IND)" submission process to regulatory authorities.
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| Figure: 03: Preclinical Study |
3. Investigational New Drug (IND) Application
Once preclinical research establishes the safety and efficacy of the drug candidate, the pharmaceutical company files an IND application with the regulatory agencies.
This submission includes all relevant preclinical data, proposed clinical trial protocols, and information on the drug substance's manufacturing process.
%20Application.png "Investigational New Drug (IND) Application") |
| Figure: 04: Investigational New Drug (IND) Application |
4. Clinical Trials
Clinical trials are a set of carefully organized experiments carried out on healthy people in order to evaluate the efficacy, dose, and safety of the drug substance. These studies are conducted under stringent restrictions & guidance.
This stage typically has four phases.
Phase I: focuses on establishing safety and dose,
Phase II: assesses efficacy and further safety, and
Phase III: entails large-scale trials to validate efficacy and track negative reactions.
Phase IV: Post-Market Surveillance
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| Figure: 05: Clinical Trial |
5. New Drug Application (NDA)
As the clinical trial study gets completed, pharmaceutical companies put all the information collectively into a "New Drug Application (NDA)".
These information are obtained throughout the aforementioned earlier stages of drug substance manufacturing. This thorough dossier contains details on the creation of medicinal substances, including information on preclinical research and clinical trial findings.
The regulatory agencies are subsequently given the NDA to evaluate and approve.
.png "New Drug Application (NDA)") |
| Figure: 06: New Drug Application (NDA) |
6. Drug Substance Manufacturing
After receipt of regulatory approval, drug substance manufacturing gets begins. The process involves multiple intricate steps, including:
A Synthesis: The drug's API is synthesized in controlled laboratory environment / conditions. The synthesis process must be consistent and reproducible, should be documented properly to ensure consistent quality as per required acceptance criteria.
B. Purification: The synthesized API is purified to remove impurities and unwanted by-products. High-performance liquid chromatography (HPLC) and other analytical techniques are employed to check and monitor the purification step, to achieve the desired purity levels.
C. Formulation: Further the Active Pharmaceutical ingredient (API) undergoes some additional processing steps to get the final drug product, such as tableting, encapsulation, or suspension in a liquid form.
D. Quality Control: Throughout the manufacturing process, rigorous quality control checks are performed to ensure the quality of API, which meets all required / desired quality specifications. Any deviations are meticulously addressed to maintain product integrity.
E. Packaging: The final drug substance (API) is carefully packaged and labeled, now at this stage it is ready for distribution to various drug product manufacturers.
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| Figure: 07: Drug Substance Manufacturing |
7. Drug Product Manufacturing
Now, drug substance (API) supplied to drug product manufacturer for formulating as final drug product. Formulation unit of drug product manufacturer formulates the APIs into the final dosage forms, such as tablets, capsules, or injectables.
The process of drug product manufacturing process follows stringent quality standards & GMP (Good Manufacturing Practices) guidelines.
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| Figure: 08: Drug Product Manufacturing |
8. Quality Assurance and Regulatory Compliance
Throughout the entire drug substance manufacturing flow, quality assurance plays a vital role. Stringent quality checks are conducted at every stage to comply with various regulatory requirements.
This ensures that the final product is safe, effective, and of the highest quality.
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| Figure: 09: Quality Assurance and Regulatory Compliance |
The drug substance manufacturing flow is an intricate and highly regulated process that plays a crucial role in bringing life-saving medicines to patients worldwide.
From the early stages of drug discovery to the final delivery of the API, each step demands precision, compliance with strict regulations, and an unwavering commitment to quality.
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