Validation in Pharmaceutical Manufacturing: Ensuring Quality and Compliance

Process validation in pharmaceutical manufacturing is a detailed procedure to ensure the manufacturing process consistently produces high-quality products. Validation processes are generally performed by validation teams such as quality assurance teams. They are usually performed before releasing new products, changing existing products, integrating new processes or equipment, or for quality control/assurance of existing methods.

Validation processes are an integral part of the manufacturing process, and every company has to design and integrate them to meet the standards. However, despite being a necessity, many must understand the importance of validation in pharmaceutical manufacturing. Therefore, here’s an overview highlighting everything you need to know about validation in pharmaceutical manufacturing.

What is the role of validation processes in pharmaceutical manufacturing?

There are several advantages of implementing validation processes in pharmaceutical manufacturing, such as ensuring quality and compliance. Here’s how successfully validation can be advantageous for pharmaceutical companies:

Enhanced product quality

The primary advantage of validation processes is that they ensure the production line manufactures products with consistent quality and up to the pre-determined quality standards. Consequently, the pharmaceutical company can sell consistent, high-value drugs that meet the market standards.

Regulatory compliance

Pharmaceutical manufacturing processes need to meet strict guidelines and standards decided by regulatory agencies. Validation processes ensure these guidelines are consistently met. Furthermore, it allows compliance lapses to be identified.

Risk mitigation

Frequent quality validation processes can be used to identify potential risks in manufacturing processes, such as equipment defects, etc. This can reduce the drop in product quality, which may result in product recalls, batch failures, etc.

Compliance with GMPs

Process validation allows pharmaceutical manufacturers to comply with good manufacturing practices (GMPs). GMPs are critical for maintaining the safety and integrity of products. These also hinder market entry, and non-compliance with GMPs may result in product recalls.

Faster market access

Process validation is a prerequisite for market entry and maintaining access to the market (i.e., to continue selling the product). The development of validation processes shows regulators and other stakeholders that the developed methods can produce high-quality products consistently and efficiently.

The development, implementation, and validation in pharmaceutical manufacturing are essential. However, a question often arises: which key validation processes must be integrated? Here’s a simple answer.

Which are the critical validation processes used in pharmaceutical manufacturing?

The critical aspects of validation include the following:

1.Process validation

Process validation ensures the manufacturing process operates according to necessary standards and requirements. During this validation, data is collected from the process design stage to the commercial production stage. Validators also use historical data and operational data to validate information.

2.Equipment validation

Equipment validation is integral to ensure that product quality remains consistently high. Generally, equipment validation is divided into three:

• Installation qualification (IQ): IQ aims to verify whether the equipment is installed according to appropriate guidelines. For example, some instruments may require sunlight, and others may need frequent air flow – all of which must be verified after installation.
• Operational qualification (OQ): OQ determines whether the equipment operates as intended. During OQ, validators check equipment parameters (e.g., temperature, noise level, cleanliness, accuracy, etc.) to determine whether they meet necessary standards.
• Performance qualification (PQ): PQ aims to verify the performance of the equipment under production conditions. Validators usually take data during operation/manufacturing.

3.Analytical method validation

Analytical methods are used to test product quality and consistency. Analytical method validation studies whether these analytical methods are reproducible and reliable. Validators study analytical methods' accuracy, precision, detection limit, range, etc.

4.Cleaning validation

Pharmaceutical manufacturing equipment must be thoroughly and frequently cleaned to ensure no contamination. Pharmaceutical companies usually create strict cleaning schedules and protocols. Cleaning validation is the validation of these cleaning schedules and protocols. Validators assess whether the protocols can efficiently remove residue. They also validate the levels of cleaning agents, cleaning time, cleaning frequency, and cleaning instruments used.

5.Computer system validation

Integrating as many technologies as possible is necessary to make manufacturing simple and efficient. However, computer systems often control these technologies, equipment, and instruments. These systems also need to be validated. This generally includes assessment of data measurement accuracy, data analytics accuracy, etc. It also assesses how, where, and why data is stored, used, and analysed.

6.Facility Validation

Last but most important is facility validation. Facility validation is performed to ensure the manufacturing facility meets the required standards. Validators assess the humidity, contamination control, temperature, light intensity, and other factors affecting product quality. Facility validation is usually performed periodically after the facility is set up.

Pharmaceutical companies generally develop these validation processes. However, the integration of such robust processes often needs to be improved. Here are some common challenges facing validation in pharmaceutical manufacturing.

Challenges facing validation in pharmaceutical manufacturing

High costs

The implementation of validation processes is expensive. Companies have to hire experts and train staff to ensure they can perform the necessary procedures. They may have to hire consultants or outsource validation, both of which are expensive.

Shifting guidelines

Regulatory guidelines constantly change, and validation processes must be updated regularly to ensure compliance. Keeping up with evolving guidelines from multiple regulatory bodies is daunting. Furthermore, different regulatory bodies and governments have different policies, increasing complexity.

Resource requirement

For validation to be effective, it must be performed by skilled personnel with expertise in quality assurance, regulatory compliance, and engineering. Companies must constantly upskill and train their staff on new guidelines and requirements.

Conclusion

Validation in pharmaceutical manufacturing is an integral process that ensures quality and compliance. It allows pharmaceutical companies to manufacture good-quality products consistently. There are six types of validation: process, equipment, analytical methods, cleaning, computer system, and facility validation. However, performing these validations takes time and effort, primarily because many resources are required, and guidelines are constantly changing. Pharmaceutical companies have made excellent strides in integrating these validations despite these challenges.

FAQs

1. How often are validation processes conducted?

Validation is performed several times: when the facility is established, during process integration, during integration of new equipment, and periodically throughout operation.

2. How is validation performed?

Validation is often performed using standard operating procedures, which the pharmaceutical company establishes according to regulatory guidelines and GMPs.

3. Is validation the same as verification in pharmaceutical manufacturing?

No. Validation ensures a process performs consistently, whereas verification confirms whether specific requirements are met.