The invention of process validation was rooted in a realization that the single testing of a finished drug product is not enough to guarantee public safety and top-notch patient care.
The FDA released the Guidance for Industry Process Validation: General Principles and Practices in 2011, emphasizing that validating manufacturing and commercialization processes are essential to ensuring product quality. To explain this concept further, here we provide a comprehensive definition of process validation as well as an overview of its three stages and their rationale.
Our ultimate goal is to help readers navigate the complexities of creating large-scale commercialization projects that meet FDA standards while still prioritizing drug quality, effectiveness, and safety.
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What is Process Validation?
According to the FDA, Process Validation is a systematic collection and assessment of data during manufacturing—from initial design right through commercial production— that confirms the process's capability in consistently producing high-quality goods.
The cornerstone of this FDA guidance document lies in the lifecycle concept. This approach not only focuses on initial drug development processes; moreover, it covers all aspects from commercial manufacturing and routine production to discontinuation of a product.
The Main Components of Pharmaceutical Process
Quality assurance is an essential part of the drug manufacturing process and should be implemented in each phase. The three stages of process validation include:
● The manufacturing procedure for a commercial product is carefully outlined and crafted in the process design stage.
● To guarantee consistent, repeatable results and operations, the design is carefully scrutinized to ensure it meets all of the necessary requirements.
● Guaranteeing Process Sustainability, Ensuring that all operational methods remain in a consistent condition of control.
Before production and commercialization, manufacturers must ensure that the products they plan to distribute meet quality standards as well as safety and efficacy regulations. It is vital that appropriate procedures are in place during manufacturing to guarantee these requirements are met.
As manufactures, it is essential to comprehend the potential variations in Active Pharmaceutical Ingredient (API) and drug products that may arise during commercialization or scaling activities.
It is necessary to do our best to understand the origin, severity, and effect of these modifications.
Strict adherence to FDA statutes is of paramount importance, and it's just as important to implement a system that will maintain regulatory compliance. Abiding By Regulatory Standards and Rules Pharmaceutical process validation activities are heavily influenced by Current Good Manufacturing Practices, otherwise known as cGMPs. These requirements must be met for legal purposes and should not be taken lightly.
● The FDA has found that a drug product is considered to be of inferior quality and will therefore become contaminated if it fails to satisfy pre-defined standards during its manufacturing, processing, packaging or storage phases. Consistent and reliable compliance with these requirements is essential for the production of safe medication.
● When collecting samples for testing purposes, it is essential to establish appropriate control standards in order to ascertain any processes in production that could be contributing to variability. All obtained specimens must accurately reflect the batch being examined as well as fulfill predetermined criteria and statistical principles of assurance.
● According to Section 211.180(e), companies must sustain a regular review process of product quality and the compliance with cGMP in order to remain compliant. Thus, perpetual analysis is critical for organizations that strive to adhere to sound manufacturing practices.
● Ultimately, cGMP requires all drug-manufacturing facilities and equipment be of suitable size and design to meet necessary standards. Moreover, every tool must undergo inspection and calibration as outlined by industry regulations.
It is essential that companies have written protocols to guarantee their products possess the specified identity, strength, quality, purity and potency. As expected by law, these procedures must be documented for production and process control regulation compliance.
General FDA Considerations and Recommendations
The FDA encourages industry leaders to adopt unified practices for data collection and other information in order to maximize accessibility of that data later down the line. By taking this step, businesses will be able to reap the rewards from their investments far into the product lifecycle.
● The FDA recommends a team-based approach to process validation, leveraging the skillsets of professionals from multiple disciplines in order to determine appropriate procedures and established practices.
● There is a vast potential for researchers to extend their knowledge of the drug product and process, as long as all protocols are adhered to. Therefore, it is strongly encouraged that studies be conducted in order to explore and observe new information.
● Every characteristic (quality, product, component) and measure (process, operating, equipment) should have controls that are equal to their level of risk in relation to the process and product.
Stage I: Process Design - Establishing Guidelines and Outcomes Creating an optimal process design is essential in order to make sure that the commercial production of a product runs smoothly and efficiently.
● Although early process design experiments do not require strict compliance with cGMP, they should be conducted in accordance with the principles of sound science.
● It is essential to maintain good documentation practices, especially when it comes to studies that aid in strengthening process understanding. Such findings should always be carefully recorded and documented.
● The FDA does not usually anticipate that continuous testing and re-testing should occur until the process fails. Process controls are introduced to guarantee product quality and reduce variability in the output. The FDA requires that process control consists of both material inspection, as well as equipment monitoring. It is especially important when:
● The product attribute is either undetectable or measurable through other methods (e.g. microbial contamination).
● When products and processes are not sufficiently documented..
Stage 2 – Qualifying the Process: Suggestions and Anticipated Results The principal purpose of process qualification is to assess whether the created process can be successfully implemented in a commercial setting.
● Ensuring your manufacturing facility is designed adequately to comply with cGMP mandates is essential.
● It is essential to carefully choose utility systems and equipment that adhere strictly to the established design specifications in order for your project to be successful.
● Ensuring that systems and equipment function within their predetermined parameters.
● The Process Performance Qualification (PPQ) requires the combination of facility, utility and equipment with trained personnel. According to FDA guidelines, objective measurements such as statistical metrics should be employed whenever possible for best results.
● Ensuring the success of process validation is heavily reliant on having written protocols and expected results. Protocol descriptions should be comprehensive, covering all aspects such as manufacturing conditions, data collection procedures, tests that need to be performed and sample plans needed for execution.
The PPQ protocol must be authorized by all applicable departments within the company, including quality assurance teams, before implementation can begin.
Stage 3 – Verification Process: Suggestions and Requirements The purpose of process verification is to guarantee the continual validation of a manufacturing process. Thus, ensuring compliance with commercial production standards and regulations.
● An essential part of the cGMP regulation is a continuous strategy to collect and evaluate information that relates to product excellence.
● Strict adherence to cGMP processes and principles is essential in order to detect any discrepancies that must be investigated and addressed.
● As advised by the FDA, monitoring and sampling should be done on an ongoing basis at a level determined during process qualification. This will provide adequate data for further analysis.
● It is imperative not to overlook the upkeep of facilities, utilities, and equipment.
A Recap and What Lies Ahead
Pharmaceutical process validation ensures that a manufacturing process is safe and secure, shielding the final product from any deviations that may be potentially hazardous to public health or disrupt supply chain operations.
Therefore, staying true to these factors is essential for the safety and efficiency of pharmaceuticals as well as high-quality patient care.
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