Department of Pharmacy, Shree Dev Bhoomi Institute of Science & Technology, Dehradun, Uttarakhand.
Pharmaceutical Validation is one of the important processes in achieving and maintaining the quality of the final drug product. If each step of the manufacturing/packing process is validated, then we can ensure that the final product is of the best quality. Pharmaceutical Process validation is an essential component for the safety of drug product and to maintain the quality of the product. Validation is establishing documented evidence which provides a high degree of assurance that a specific process for manufacturing tablets will consistently produce a product meeting its pre-determined specifications and quality attributes. Validation and quality assurance will go hand in hand, ensuring the quality of the products. The present article gives an introduction and general overview on process validation of Ursodeoxycholic Acid tablets.
Process validation is a methodical process intended to ensure that a manufacturing process can reliably provide highquality products.It is carried out by a validation team under the direction of the pharmaceutical industry's quality assurance head.Process validation is typically carried out before a new product is released, whenever changes are made to an existing product, and on a regular basis to check the process.protocol should be established at the beginning of the validation process that outlines the parameters to be monitored, the samples to be collected, and the results to be accepted. Process validation ensures that the manufacturing process consistently produces high-quality products that meet regulatory requirements and align with industry standards. It offers uniformity, weight, and dosage across batches, complies with quality benchmarks for attributes such as dissolution and hardness, and ensures regulatory adherence through documented evidence of reliability. In summary, process validation is essential for maintaining consistency, quality, and compliance in tablet manufacturing. Drug product development is a sophisticated process that involves drug discovery, laboratory testing, animal studies, clinical trials, and regulatory registration. Process controls include inspection of raw materials and packing materials, in-process controls, and targets for the final product. Process validation includes monitoring each process involved in the whole manufacturing process to produce high-quality, efficient, and safe products. Process validation is an integral part of CGMPs (Current Good Manufacturing Practices). The requirement of process validation appears as the regulatory agency's requirement to ensure that the product manufactured is consistent, safe, and reliable throughout its lifecycle. Ursodeoxycholic Acid, a secondary bile acid naturally found in small quantities in human bile, plays a pivotal role in reducing the cytotoxic effects of endogenous bile acids. Its therapeutic applications extend to dissolving gallstones, treating primary biliary cholangitis, and improving liver enzyme profiles in patients with chronic liver diseases. UDCA achieves these effects through multiple mechanisms, including reducing cholesterol saturation in bile, exerting cytoprotective effects on hepatocytes, and modulating the immune response. Liver diseases represent a significant global health challenge, with millions of people affected annually by conditions such as cholestatic liver diseases, non-alcoholic fatty liver disease (NAFLD), and primary biliary cholangitis (PBC). These disorders often result from impaired bile flow, leading to bile acid accumulation, which exacerbates liver damage and systemic complications. Among various therapeutic agents, Ursodeoxycholic Acid (UDCA) has emerged as a cornerstone treatment for hepatobiliary disorders, particularly those involving cholestasis. Despite its established efficacy, the formulation and stability of Ursodeoxycholic Acid Tablets IP 300 mg remain critical areas of research. UDCA's poor aqueous solubility and sensitivity to environmental conditions such as heat and humidity present significant challenges in maintaining its therapeutic efficacy over time. Additionally, ensuring patient compliance through optimized dosage forms and minimizing adverse effects are vital for achieving desired clinical outcomes. In recent years, advancements in pharmaceutical formulation technologies have opened new avenues to address these challenges. From enhancing solubility using novel excipients to improving tablet stability through advanced coating techniques, these innovations aim to optimize the therapeutic potential of UDCA. This study seeks to explore the formulation, quality control, and stability aspects of Ursodeoxycholic Acid Tablets IP 300 mg, aiming to overcome the limitations of current products and contribute to improved patient outcomes in the management of liver diseases. By evaluating critical parameters such as dissolution profiles, impurity levels, and stability under varying environmental conditions, this research intends to provide a comprehensive framework for developing a robust and effective UDCA tablet formulation. Ursodeoxycholic Acid (UDCA), a naturally occurring bile acid, is widely used in the treatment of cholestatic liver diseases and gallstone dissolution. As an essential pharmaceutical agent, UDCA Tablets IP 300 mg play a critical role in enhancing bile flow and protecting hepatocytes from bile acid-induced injury. The drug's significance lies in its multifaceted therapeutic applications, pharmacokinetics, and safety profile, making it an important subject for pharmaceutical research. Liver diseases, including conditions like Primary Biliary Cholangitis (PBC), gallstones, and liver dysfunctions, are emerging as significant global health challenges. These disorders are characterized by progressive liver damage, altered bile flow, and disturbances in bile acid metabolism, leading to complications such as cirrhosis, liver failure, and an increased risk of liver transplantation. With rising prevalence rates worldwide, there is an urgent need for effective, reliable treatments that can improve liver function, alleviate symptoms, and prevent disease progression. In this context, Ursodeoxycholic Acid (UDCA), a naturally occurring bile acid, has become a cornerstone in the treatment of several liver and gallbladder-related conditions.
VALIDATION
Validation is the documented act proving that any procedure, process, equipment, material, activity, or system leads to the expected result. Validation as defined in ICH Q7 - ‘Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.’ Validation defined in ICH Q8(R2)/Q11 - Continuous Process Verification is an alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated.
WHO - Process validation. The collection and evaluation of data, throughout the product life cycle, which provides documented scientific evidence that a process is capable of consistently delivering quality products.
ISO definition - Validation is the confirmation by examination and the provision of objective evidence that the requirements for a specific intended use are fulfilled.
FDA Process validation: -
process validation is defined as the collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products. Process validation involves a series of activities taking place over the lifecycle of the product and process. This guidance describes process validation activities in three stages.
Health Canada Process validation - The collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products. Validation is not a single study - it represents the cumulative knowledge gained during product development and manufacturing.
Importance of Validation
A key component of industrial quality assurance, especially in sectors like biotechnology and pharmaceuticals, is process validation. It assures that manufacturing procedures continuously produce products that fulfill predetermined standards and requirements for quality. When a process validation is carried out correctly, producers can: Process parameters and controls are determined during the validation of any process or system.
History of Process Validation
This concept was first introduced in the mid-1970s for improving the quality of pharmaceuticals by two Food and Drug Administration (FDA) officers, Ted Byers and Bud Loftus [1] In 1987, the FDA released the first process validation guidance.[4] The fundamental approach was testing the process to ensure it worked, along with periodic retesting of the manufacturing process to ensure it continued to work. In the mid-2000s, regulatory agencies developed ICH Q8 – Pharmaceutical Development to provide foundational concepts required for companies to develop high-quality manufacturing processes. The final 2009 guidance provided several definitions intended to provide the basis for very important concepts for building processes [5]
Stages of Process Validation
In their definition of process validation, the USFDA places a strong emphasis on data collection and analysis. In order to understand the causes of variation and control it appropriately, the validation team must not only collect data on the activities that take place across the product and process lifecycle, but also analyze that data. The 3 stages of process validation are process design, process qualification, and continued process verification:
Approaches in Process Validation
Figure 2: Approaches of Process Validation
Stage 1: Process Design
During the PD stage, the manufacturing procedure is set up to replicate the delivery of a medication that satisfies pre-established requirements and quality standards. The validation team must have a thorough understanding of the process's real operation in order to accomplish this. Take into account the following resources and techniques for gathering process data: Product development activities
• Functionality and limitations of production equipment
• Predicted contributions to variability
• Design of experiment (DOE) studies
• Risk analysis tools
• Experiments or demonstrations at laboratory or pilot scale
• Computer-based or virtual simulations
Process design stage also involves process control, planning & strategies to reduce input variation or adjust for it during manufacturing. Process controls commonly consist of material analysis and equipment monitoring at significant processing points. In some cases, the use of process analytical technology (PAT) may be needed.
Stage 2: Process Qualification
This stage of process validation consists of process design evaluation to determine if it is effective for qualitative production. First, the production facility should be designed according to the requirements of current good manufacturing practice (CGMP). Next, qualification of utilities and equipment should be conducted such as making sure that they are built and installed in compliance with design specifications. Finally, process performance qualification should be executed through a protocol and documented in a report:
Stage 3: Continued Process Verification
After PD & PQ stages, the third stage of process validation deals with setting of the systems to continually ensure that the validated process will remain in such a state during routine production. Continued process verification often incorporates the use of statistical process control (SPC), the continuous monitoring and sampling of process parameters and quality attributes, and the scheduled maintenance of the facility, utilities, equipment, and related assets. It is essential for good documentation practices to be employed throughout the validation process.
Types of Process Validation
The Process validation is often classified according to the time it is performed in relation to the production schedules. Based on this description, there are 4 types of process validations:
Type 1: Prospective Validation
It is implemented when any product will be manufactured with a new formula or within a new facility. Also known as premarket validation, prospective validation is usually carried out before commencing routine production. It is also considered as the foundational type of validation because it is the starting point for any product that will be released under new conditions.
Type 2: Retrospective Validation
It is conducted only when the manufacturing process has not formally undergone a documented validation. Retrospective validation is normally fulfilled with the use of historical data and trends analysis to provide evidence that the process is at a state that it is intended to be in. In most cases, it is no longer an acceptable approach to process validation because any product should have already been validated before its commercial distribution.
Type 3: Concurrent Validation
It is done during regular pharmaceutical production to demonstrate that the process performs at the level that it should in the course of its actual execution. While concurrent validation is still an acceptable approach to process validation under certain circumstances (e.g. manufacturing medically necessary drugs in coordination with the USFDA to prevent a short supply), the agency continues to emphasize that it should only be used rarely. Recently, an FDA inspection revealed that a US-based manufacturer produced adulterated drug products. To correct their violations, the pharmaceutical company responded with an intention to implement concurrent validation. However, the USFDA warned against it because they failed to show a clear understanding of variability sources in their manufacturing processes. Instead, the agency required them to comply with specific CGMP regulations, including adequately validating manufacturing processes.
Type 4: Revalidation
Revalidation is more widely used for medical devices than drug products. It is executed when prospective validation reaches a conclusion that the manufacturing process is unable to produce the product consistently. Moreover, a criteria for revalidation may be indicated in the original validation protocol. The revalidation process may not be as comprehensive as the initial validation, especially if the situation only calls for some aspects to be repeated.
Stages & Steps during Process validation of Ursodeoxycholic Acid Tablets IP 300 mg:
CONCLUSION
Validation is an integral part of the pharmaceutical industry, meeting the regulatory guidelines to produce a safe, high-quality product. The above review shows the importance of validation for the pharmaceutical platform, which is a regulatory agency's requirement nowadays to produce a consistent, reliable, and safe product.
ACKNOWLEDGEMENT
I would like to express my sincere gratitude to the teachers for their support and guidance throughout the completion of this project. I would like to acknowledge our principal, Prof. (Dr.) Shivanand Patil, Director, Division of Pharmacy, Shree Dev Bhoomi Institute of Science & Technology, Dehradun, for fostering a supportive environment that encourages collaboration and teamwork. I also want to extend my thanks to my teacher, Obed Singh, Associate Professor, Division of Pharmacy, Shree Dev Bhoomi Institute of Science & Technology, Dehradun for guiding me and providing support and encouragement helped me stay on track and overcome any challenges that I faced for the completion of “A REVIEW ON PROCESS VALIDATION OF URSODEOXYCHOLIC ACID TABLETS IP 300 mg”. Huge thanks to the library staff for providing access to valuable resources and materials that were essential to the success of the project.
REFERENCES
Vaibhav*, Obed Singh, Shivanand Patil, A Review on Process Validation of Ursodeoxycholic Acid Tablets Ip 300 Mg, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 5, 3524-3531. https://doi.org/10.5281/zenodo.15476783
10.5281/zenodo.15476783
