How to make a Process Validation in 3 steps.

CIQA Process Validation



Process Validation means “establishing by objective evidence that a process constantly produces a result or product meeting its predetermined specifications.”

In other words, 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 a quality product.”

Typically, the process validation considers the most relevant and critical operating parameters of the system at the full range established and recommended by the specific product’s specifications at the intended use.

FDA Guidance for Industry: Process Validation:

General Principles and Practices

This guidance outlines the general principles and approaches that the FDA considers to be 21 appropriate elements of process validation for the manufacture of human and animal drug and 22 biological products, including active pharmaceutical ingredients (API or drug substance). For more information refer to httpss://

Performance Qualification (PQ) is NOT equal to Process Validation (PV).

Some people confuse performance qualification with process validation.

Performance qualification is just one activity of the whole process of validation activities required to be done by the FDA statutory and regulatory requirements for process validation.  For more information about performance qualifications, click here.

Performance Qualification (PQ) Definition

The Performance Qualification is a collection of test cases used to verify that a system behaves as expected under simulated or real-world conditions demonstrating that the process or equipment is consistent over time with the user’s requirements and functional requirement specifications.

The term “qualification” refers to activities undertaken to demonstrate that utilities and equipment are suitable for their intended use and perform properly.

During the (PQ), the process design is evaluated to determine if it is capable of a reliable and controlled commercial manufacture within specifications.  In this phase, the PQ aims to verify and document that the equipment is working with reproducible results within a specific production working range.

Instead of testing components and instruments one-by-one, PQ tests them all as a whole and overall process.  Depending on the size and complexity of the system, Performance Qualification PQ-E and PPQ can be combined in the same protocol document(s) with Installation Qualification or Operational Qualification.  But, the testing must be performed and executed in established chronological order: IQ first, OQ second, and PQ third.

The protocol must be prepared as per the FDA guideline “Process Validation: General Principles and Practices,” which officially defines the PROCESS VALIDATION into three (3) steps elements: httpss://

Step 1. Design of the facility and qualification of the equipment and utilities (sometimes called by the industry as PQ-E)

The PQ-E generally includes the following activities:

• Selecting utilities and equipment construction materials, operating principles, and performance characteristics based on whether they are appropriate for their specific uses.

• Verifying that utility systems and equipment are built and installed in compliance with the design specifications (e.g., built as designed with proper materials, capacity, and functions, and properly connected and calibrated).

• Verifying that utility systems and equipment operate in accordance with the process requirements in all anticipated operating ranges. This should include challenging the equipment or system functions while under load comparable to that expected during routine production. It should also include the performance of interventions, stoppage, and start-up as is expected during routine production. Operating ranges should be shown capable of being held as long as would be necessary during routine production.

Step 2. Process Performance Qualification (PPQ)

The Process Performance Qualification (PPQ) protocol is a fundamental component to demonstrate how the equipment or system achieves and run. Its purpose is to ensure ongoing product quality by documenting performance over a period of time for certain processes.

The PPQ combines the actual facility, utilities, equipment (each now qualified), and the trained personnel with the commercial manufacturing process, control procedures, and components to produce commercial batches.

A successful PPQ will confirm the process design and demonstrate that the commercial manufacturing process performs as expected using objective measures (e.g., statistical metrics) wherever feasible and meaningful to achieve adequate assurance.

Data from laboratory and pilot studies can provide additional assurance that the commercial manufacturing process performs as expected.

PPQ will have a higher level of sampling, additional testing, and greater scrutiny of process performance than would be typical of routine commercial production.

A written protocol that specifies the manufacturing conditions, controls, testing, and expected outcomes is essential for this stage of process validation.

The PPQ protocol generally includes the following activities:

• The manufacturing conditions, including operating parameters, processing limits, and component (raw material) inputs.

• The data to be collected and when and how it will be evaluated.

• Tests to be performed (in-process, release, characterization) and acceptance criteria for each significant processing step.

• The sampling plan, including sampling points, number of samples, and the frequency of sampling for each unit operation and attribute. The number of samples should be adequate to provide sufficient statistical confidence of quality both within a batch and between batches. The confidence level selected can be based on risk analysis as it relates to the particular attribute under examination. Sampling during this stage should be more extensive than is typical during routine production.

• Criteria and process performance indicators that allow for a science- and risk-based decision about the ability of the process to consistently produce quality products. The criteria should include:

— A description of the statistical methods to be used in analyzing all collected data (e.g., statistical metrics defining both intra-batch and inter-batch variability).

— Provision for addressing deviations from expected conditions and handling of nonconforming data. Data should not be excluded from further consideration in terms of PPQ without a documented, science-based justification.

• Design of facilities and the qualification of utilities and equipment, personnel training and qualification, and verification of material sources (components and container/closures), if not previously accomplished.

• Status of the validation of analytical methods used in measuring the process, in-process materials, and the product.

• Review and approval of the protocol by appropriate departments and the quality unit.

Step 3.  – Process Verification:

Ongoing assurance is gained during routine production that the process remains in a state of control.

The goal of the third validation stage is a continual assurance that the process remains in a state of control (the validated state) during commercial manufacture. A system or systems for detecting unplanned departures from the process as designed is essential to accomplish this goal.

Adherence to the CGMP requirements, specifically, the collection and evaluation of information and data about the performance of the process, will allow the detection of undesired process variability. Evaluating the performance of the process identifies problems and determines whether action must be taken to correct, anticipate, and prevent problems so that the process remains in control.

An ongoing program to collect and analyze product and process data that relate to product quality must be established. The data collected should include relevant process trends and quality of incoming materials or components, in-process material, and finished products.

The data should be statistically trended and reviewed by trained personnel. The information collected should verify that the quality attributes are being appropriately controlled throughout the process.

It requires a statistician or person with adequate training in statistical process control techniques to develop the data collection plan and statistical methods and procedures used in measuring and evaluating process stability and process capability.  Procedures should describe how trending and calculations are to be performed and should guard against overreaction to individual events as well as against failure to detect unintended process variability.

Production data should be collected to evaluate process stability and capability. The quality unit should review this information. If properly carried out, these efforts can identify variability in the process and/or signal potential process improvements.

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More details on specific FDA expectations for PQ and PPQ can be found in the guidance document below. httpss://

Three (3) options to create a Process Validation Protocol

Option 1. You can create a great protocol, using a template.

You can download a free sample of a validation template in .pdf format. 

To see the complete list of the most popular validation templates, click here.

In addition, you can request a quotation to buy online a full validation template document in MS Word format that is completely editable, ready to fill, and adapt to your needs.

Option 2. We can bring you a formal training on how to create your own validation protocols using our template(s).

This option is recommended if you want to learn more about how to build a robust validation protocol. One of our expert(s) will provide online step-by-step training to your team (unlimited assistance) on how to build a reliable validation protocol using a template. You can improve your corporate validation procedures and policies incorporating our template sections.  It includes the template, an exam, and a training certificate for each assistant.  Request a quote now.

Option 3. We can create a customized process validation.

One of our expert(s) will create and prepare for you a customized validation protocol with the inputs and specific information of your company. It may include, online support in document creation, execution, or final reporting, Request a quote online.




Validation for drugs (finished pharmaceuticals and components) is a legally enforceable requirement under section 501(a)(2)(B) of the Act (21 U.S.C. 351(a)(2)(B)), which states the following:

“… a drug (including a drug contained in a medicated feed) shall be deemed to be adulterated if the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirement of the act as to the safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.”

Process validation for drugs (finished pharmaceuticals and components) is a legally enforceable requirement under section 501(a)(2)(B) of the Act (21 U.S.C. 351(a)(2)(B)), which states the following:

FDA regulations describing current good manufacturing practice (CGMP) for finished pharmaceuticals are provided in 21 CFR parts 210 and 211.

The CGMP regulations require that manufacturing processes be designed and controlled to assure that in-process material and the finished product meet predetermined quality requirements and do so consistently and reliably.

Process validation is required, in both general and specific terms, by the CGMP regulations in parts 210 and 211. The foundation for process validation is provided in § 211.100(a), which states that “[t]here shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess…” (emphasis added). This regulation requires manufacturers to design a process, including operations and controls, which results in a product meeting these attributes.

Other CGMP regulations define the various aspects of validation. For example, § 211.110(a), Sampling and testing of in-process materials and drug products, requires that control procedures “. . . be established to monitor the output and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product” (emphasis added).

Under this regulation, even well-designed processes must include in-process control procedures to assure final product quality. In addition, the CGMP regulations regarding sampling set forth a number of requirements for validation:

Samples must represent the batch under analysis (§ 211.160(b)(3)); the sampling plan must result in statistical confidence (§ 211.165(c) and (d)); and the batch must meet its predetermined specifications (§ 211.165(a)).

In addition to sampling requirements, the CGMP regulations also provide norms for establishing in-process specifications as an aspect of process validation. Section 211.110(b) establishes two principles to follow when establishing in-process specifications. The first principle is that

“. . . in-process specifications for such characteristics [of in-process material and the drug product] shall be consistent with drug product final specifications . . . .”

Accordingly, in-process material should be controlled to assure that the final drug product will meet its quality requirements. The second principle in this regulation further requires that in-process specifications “. . . shall be derived from previous acceptable process average and process variability estimates where possible and determined by the application of suitable statistical procedures where appropriate.”

This requirement, in part, establishes the need for manufacturers to analyze process performance and control batch-to-batch variability.

The CGMP regulations also describe and define activities connected with process design, development, and maintenance. Section 211.180(e) requires that information and data about product quality and manufacturing experience be periodically reviewed to determine whether any changes to the established process are warranted. Ongoing feedback about product quality and process performance is an essential feature of process maintenance.

In addition, the CGMP regulations require that facilities in which drugs are manufactured be of suitable size, construction, and location to facilitate proper operations (§ 211.42). Equipment must be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use (§ 211.63). Automated, mechanical, and electronic equipment must be calibrated, inspected, or checked according to a written program designed to assure proper performance (§ 211.68).












Related topics and resources:

Validation Plan, Installation Qualification, Operational Qualification, Performance Qualifications, Component Qualification, Traceability Matrix, Ppk, Control Charts, Cpk, User Requirements, Functional Requirement Specifications, GAMP5, risk assessment

Picture of Ramon Cayuela, MS, BS, Chemical Engineering

Ramon Cayuela, MS, BS, Chemical Engineering

CIQA President and CEO.
I've been working in validation engineering since 1992 with many multinational pharmaceutical companies. I love sharing my passion and knowledge with others. If you have any questions about anything (or just have general questions). I will be more than happy to assist you. You can count on the BEST customer service on CIQA. I go to great lengths to make sure my clients are 100% satisfied with their purchases and check emails/messages consistently throughout the day. You can rest assured that everything being sold here is as-described or your money back. I look forward to working with you!