• Validation
  • Validation

    What is Validation ?

    Validation is a process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in production or testing maintains the desired level of compliance at all stages. In Pharma Industry it is very important apart from final testing and compliance of product with standard that the process adapted to produce itself must assure that process will consistently produce the expected results. Here the desired results are established in terms of specifications for outcome of the process. Qualification of systems and equipment is therefore a part of process of validation. It is a requirement of food and drug, pharmaceutical regulating agencies like FDA's good manufacturing practices guidelines.


    Since a wide variety of procedures, processes, and activities need to be validated, the field of validation is divided into a number of subsections including the following:

    • Equipment validation
    • Facilities validation
    • HVAC system validation
    • Cleaning validation
    • Process Validation
    • Analytical method validation
    • Computer system validation
    • Packaging validation
    • Cold chain validation

    Reasons for Validation ?

    FDA, or any other food and drugs regulatory agency around the globe not only ask for a product that meets its specification but also require a process, procedures, intermediate stages of inspections, and testing adopted during manufacturing are designed such that when they are adopted they produce consistently similar, reproducible, desired results which meet the quality standard of product being manufactured, such procedures are developed through the process of validation. This is to maintain and assure a higher degree of quality of food and drug products. Validation is "Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes.". A properly designed system will provide a high degree of assurance that every step, process, and change has been properly evaluated before its implementation. Testing a sample of a final product is not considered sufficient evidence that every product within a batch meets the required specification.

    CSV/PLC Validation:

    Computerized System Validation for PLC based system

    Drugs are essential for maintaining human life and health, while they have significant influence on the human body. This requires proper quality of drugs medicines. In order to produce drugs with proper quality, appropriate production processes are necessary in addition to use of proper raw materials and their blending percentage. Drugs have been produced manually in the past. Recently, however, they are produced by production facilities that are automatically controlled by CS in order to enhance production efficiency. Therefore, proper workability and operability of CS has become more important. On the other hand, there exist issues that poor quality drugs are produced due to the malfunction of CS. For this reason, the regulatory authorities required drug production companies to prove that their drug production processes and CS that controls such processes are adequate to produce high-quality drugs by showing evidence based on documents or electronic data regarding drug development and verification. The procedure that proves the adequacy of the production processes is referred to as Process Validation (PV), while the procedure that proves the adequacy of the CS used for production is referred to as Computerized System Validation (CSV).

    Usually, PV and CSV procedures are implemented in a parallel manner along development when production facilities are built. At first, the CSV standards are stipulated according to each country that produces and sells drugs. Therefore, export of drugs on which CSV is conducted in accordance with the export country requirements must also be conducted again to meet the CSV standards of the importing country. Since a lot of labor is needed to conduct CSV, this has actually produce significant work load on drug production companies. Therefore, the International Society for Pharmaceutical Engineering proposed CSV standards that incorporate the CSV standards of each country. These standards are referred to as the Good Automated Manufacturing Practice (GAMP). Implementation of CSV in accordance with GAMP makes it comparatively easier to export drugs to other countries. Therefore, GAMP has become the de facto CSV standard. Currently, the fifth edition of GAMP is being used.

    Outline of PLC based Computerized System and Validation Procedure:

    PLC is a controller that can store programs that are equivalent to relay circuits which control processes. PLC consists of the common part that is fully in accordance with the integrated regulations, and parts that are individually different depending on each manufacturer. Each part is an independent computer called a unit, and each of the parts is interactively connected with other units or networks. The common part is written in the programming language It would be expected that the regulated user’s Validation Policy or Validation.

    Validation Master Plan (VMP) should identify the company’s approach to validation and its overall philosophy with respect to computerized systems. The VMP should: Identify which computerized systems are subject to validation. Provide brief descriptions of the validation strategies for different categories of computerized systems as well as other validation activities. Outline protocols and related test procedures for all validation activities including computer systems. Define reporting requirements to document validation exercises and related results. Identify key personnel and their responsibilities as part of the Validation Program.

    Our Experience:

    Integral Solutions Engineers are experienced in the validation of PLC and SCADA systems, of various industrial facilities. We are able to assist in the Development of the VALIDATION MASTER PLAN and executing it accordingly.

    In the real business world, it has often been seen that validation professionals from pharmaceutical companies lack practical experience in relation to the development and use of PLC application software. Also, control system integrators or system suppliers are not trained in current good manufacturing practices (cGMP) or good X practices (GxP) relating to Food and Drug Administration (FDA) compliance where ‘x’ can mean clinical, laboratory, manufacturing, pharmaceutical and others. They also do not possess the solid validation operational experience required for FDA compliance. The know-how gap between supplier and users in the pharmaceutical industry is obvious, and problems caused by this gap can be numerous. As a result, good automation manufacturing practice (GAMP) has come into being to address these issues as it considers the overall automation system validation methodology.

    Yet, even GAMP serves to provide a guideline only rather than dealing with practical development of the PLC cycle.

    Therefore, the emphasis is on good engineering practice (GEP) which ensures that engineering or software development methodology generates deliverables that support the requirement for qualification or validation in the pharmaceutical industry. The control system integrator or system supplier must plan a software development strategy that holds the key to a successful compliant system.

    Good Manufacturing Practice (GMP) in Process Plants:

    Today’s control software packages use a variety of programming languages such as function blocks, ladder logic, sequential function charts, etc. These programs must be clearly documented and easy to update in order to improve the plant’s productivity over its expected life. A simple, universal system of matrix-based documentation can be easily developed jointly by the process control system engineers and production engineers.

    Such a methodology of documentation has been created and applied to several batch control plants, the most recent of which are several multirecipe, multi-product specialty chemical plants. This concept of software documentation, which involves mainly the sequence control and safety interlock logic functions, has proven to be an effective way to transfer process technology and operational know-how of an existing pilot scale operation to a new, fully automated, large-scale production plant.

    The Validation Process:

    The validation scope, boundaries and responsibilities for each process or groups of similar processes or similar equipment's must be documented and approved in a validation plan. These documents, terms and references for the protocol authors are for use in setting the scope of their protocols. It must be based on a Validation Risk Assessment (VRA) to ensure that the scope of validation being authorized is appropriate for the complexity and importance of the equipment or process under validation. Within the references given in the VP the protocol authors must ensure that all aspects of the process or equipment under qualification; that may affect the efficacy, quality and or records of the product are properly qualified.

    Validation Process

    Good Manufacturing Practice (GMP) in Process Plants:

    Design qualification (DQ) - Demonstrates that the proposed design (or the existing design for an off-the-shelf item) will satisfy all the requirements that are defined and detailed in the User Requirements Specification (URS). Satisfactory execution of the DQ is a mandatory requirement before construction (or procurement) of the new design can be authorized.

    Installation qualification (IQ) – Demonstrates that the process or equipment meets all specifications, is installed correctly, and all required components and documentation needed for continued operation are installed and in place.

    Operational qualification (OQ) –Demonstrates that all facets of the process or equipment are operating correctly.

    Performance qualification (PQ) – Demonstrates that the process or equipment performs as intended in a consistent manner over time.

    Component qualification (CQ) – is a relatively new term developed in 2005. This term refers to the manufacturing of auxiliary components to ensure that they are manufactured to the correct design criteria. This could include packaging components such as folding cartons, shipping cases, labels or even phase change material. All of these components must have some type of random inspection to ensure that the third party manufacturer's process is consistently producing components that are used in the world of GMP at drug or biologic manufacturer.

      Although PQ is described as a separate activity, it may in some cases be appropriate to perform it in conjunction with OQ  

    Qualification includes the following steps:

    Good Manufacturer