Facility Validation in pharmaceutical Pharma Company

Facility Validation in Pharmaceutical Pharma Company

Facility qualification (a part of validation that proves and documents that equipment or ancillary systems are properly installed, work correctly, and lead to the expected results), and validation (establishing documented evidence that provides a high degree of assurance that the manufacturing processes, including buildings, systems, and equipment consistently produce the desired results according to predetermined specifications and quality attributes) activities will establish and provide documentary evidence that:

The premises, supporting utilities, equipment, and processes have been designed under the requirements of GMP. This constitutes Design Qualification (DQ).

The premises, supporting utilities, and equipment have been built and installed in compliance with their design specifications. This constitutes Installation Qualification (IQ).

The facilities, supporting utilities, and equipment operate under their design specifications. This constitutes Operational Qualification (OQ).

The facilities, utilities, or equipment that can affect product quality, perform as intended meeting predetermined acceptance criteria. This constitutes Equipment Performance Qualification (EPQ) Once the facility has been validated (IQ + OQ + Performance Qualification ), then process validation can commence

A specific process will consistently produce a product meeting predetermined specifications and quality attributes. This constitutes Process Validation (PV) or Process Performance Qualification (PPQ).

Establishing a project team that has adequate skills that are appropriate for the size and complexity of the project is key to the project launch. Project team representation should be based on the project scope, resource requirements, and key stakeholdersFacility and Utility Validation Basic Concept:

Facility and Utility Validation Rationale
Installation and Operational Qualification exercises assure through appropriate performance tests and related documentation and records that facilities and utilities have been commissioned correctly and that all will be reliable and within prescribed or specified operating limits.
The validation approach will be based on a risk assessment under SOP for Quality Risk Management and/or the impact assessment outlined in the SOP Validation Impact Assessment Procedure.  If the utility directly affects product quality then qualification of the utility will be performed as described in this section. If the utility does not directly affect product quality qualification may not be required. Justification for not qualifying the utility is required to be approved by Quality. Facility Qualification will be performed in GMP areas only.
Validation Project Plan
For large-scale projects, a Validation Project Plan (VPP) should be written. VPPs represent dynamic, project-specific master validation plans, often accompanied by several appendices that change as the project progresses.
Design Qualification
The first element of the validation of the new facilities and utilities is Design Qualification (DQ). The DQ documents that the design of facilities and utilities meets GMP, process user, and safety requirements and is suitable for its intended use. The DQ process can be incorporated into the IQ or validation report.
Installation Qualification
Installation Qualification (IQ) provides documented evidence that the facilities and utilities have been installed under their design specifications, user requirements, and manufacturer recommendations.  Furthermore, IQ ensures that a record of the principal features of the facilities and utilities, as installed, is available and that it is supported by adequate documentation to enable satisfactory operation, maintenance, and change control to be implemented.
Installation Qualification (IQ) should be performed on new or modified facilities and utilities.  IQ should include an appropriate, but not limited to the following:
tp -Installation of piping, services, and instrumentation checked to current engineering drawings and specifications;
tp -Collection and collation of supplier operating and working instructions and maintenance requirements;
tp -Calibration requirements;
tp -Verification of materials of construction;
tp -Cleaning and passivation results;
tp -Pressure testing/weld checks/pipe slope isometrics;
tp -Safety requirements;
tp -Training.
Operational Qualification
Operational Qualification (OQ) provides documented evidence that the utility operates as intended throughout the specified design or anticipated operating ranges and complies with GMP, OHS legislation, and other relevant standards.
The critical operating parameters of the utility should be identified at the Operational Qualification stage.  The plans/protocols for the Operational Qualification should identify the studies to be undertaken on the critical variables, the sequence of those studies and the measuring equipment to be used, and the acceptance criteria to be met.
Where applicable, a simulated product may be used to conduct the Operational Qualification. Studies on the critical variables should include worst-case conditions.
All testing equipment should be identified in the protocol and calibrated before use.
All critical instruments will be calibrated before Operational Qualification.
Where sampling is performed, the specific sampling site must be identified in the protocol.
Commissioning performed following installation is not a substitute for OQ, however, if the commissioning is documented and witnessed/reviewed by a Site employee, the results may be used as part of the OQ.
The completion of satisfactory Installation Qualification and Operational Qualification exercises should permit a formal ‘release’ of the facility/utility for the next stage in the validation exercise. This release should be documented through the completion of the validation exercise.
Facility / Utility Validation Requirements
Protocols for each type of qualification will be written according to the site SOP.  Depending on the size of the system or item to be validated IQ and OQ may be combined into one protocol and one report.
For new utilities where possible, the manufacturer’s validation package will be reviewed and if suitable purchased. The validation team will make additions to the package as necessary to meet site quality standards.  Vendor protocols must be pre-approved by the site to meet in-house requirements as outlined in this document. A validation report will be issued for vendor protocols.
When there is more than one identical building or utility, each has to be qualified however identical protocols can be used.
Where operating manuals exist for a utility, protocols should reference these manuals.
Validation reports will be written for each protocol. Protocols written for specific utilities must adequately describe the intended use.
An EH&S risk assessment will be considered an essential part of any utility protocol.
The acceptance criteria for each item will be described and justified in the specific protocols for that item. Generally, the facility/utility must conform to GMP requirements, OHS standards, and applicable Australian standards.
Any deviations encountered during the validation study must be documented in the validation protocol/report and must be approved by Quality Operations.
Qualification of Existing Facilities and Utilities
For established facilities and utilities with critical aspects that are not validated, gaps in qualification activities in the existing documentation shall be identified.  If there are gaps, remediation activities shall be developed and implemented.
Qualification of Utilities with Computer Systems
Utilities containing Programmable Logic Controllers and or computer systems must also conform to SOP Computer Validation Guidelines. Usually, the computer system will be qualified as part of the utility qualification. Separate protocol(s) and report(s) are not required.

Re-Qualification Criteria
Modifications to, or relocation of, validated facilities and utilities must be authorized through the change control system. Modification or relocation will require full or partial requalification.
Continuous Maintaining the Validated State
All facilities and utilities once validated will be maintained in a validated state throughout the life cycle of the facility/utility.  Maintaining the validated state will be achieved by the change control system, re-qualification, training, SOPs, calibration, and engineering maintenance programs.

Examples of facility qualification

In this chapter, the various components of facility qualification are illustrated by practical examples.

1 Design qualification

All essential parameters for the subsequent use of pharmaceutical process equipment are defined in the specification (also known as user requirements). Together with the technical specification (the approved supplier specification), this is an important part of the design qualification (DQ). Checks are carried out throughout the remaining qualification modules (IQ/OQ) to verify whether the facility meets the requirements of the specification.

  • Description of facility
  • Functionality
  • Procedural description
  • Accessory
  • Mechanical components
  • Version
  • Dimensions
  • Materials
  • Control and process monitoring
  • Supply of energy and utilities
  • Constructional prerequisites
  • Installation, start-up, and acceptance tests
  • Documentation, validation, qualification
  • Appendix: drawings, internal guidelines

In the following, the specification for a washer is shown as an example:

Preliminary remark

This specification describes the minimum delivery scope for a facility that cleans, disinfects, and dries equipment intended for use in the pharmaceutical industry. This document does not provide a comprehensive or complete description of the system to be delivered. Instead, it defines a minimum technical standard and refers to standards and specifications applicable in this case.

Direct references to standards rules and regulations

The following standards rules and regulations must be taken into consideration during the design and construction of automatic washers. This also applies to specifications not stated here that are relevant to the construction of the facility.

  • EU GMP Guideline of good manufacturing practice for medicinal products
  • Current Good Manufacturing Regulations and Guidelines (cGMP) of the US Food and Drug Administration (FDA)

Description of facility

Functionality: automatic cleaning, drying, and disinfection of pharmaceutical equipment. Cleaning is carried out using water with varying qualities to which a cleansing agent is added depending on the program step. The final rinse must be carried out using purified water.

Description of procedure: A standard cleaning procedure. The tenside-based cleaners are specified.

  • Accessories: washing baskets
  • Figure 2 Rinsing programme
  • Rinsing programme
  • Prewash
  • Main wash with tenside-based cleaner
  • Repeat the main wash cycle, as required
  • Rinsing in cycle
  • Clear rinse with purified water in a single operation
  • Drying
  • Cooling
  • Mechanical components

Full drainage of machine and pumps; no exposed heating elements; variable partitioning of internal compartment Pharma-compliant version characterized by: use of material 316L for all surfaces and pipes coming into contact with fluids, use of diaphragm valves and tri-clamp connections, dead volume-free and fully drainable installation, prevention of mixup or reverse contamination and use of a validatable process control and machine documentation.programmable liquid metering pumps for cleaning fluids with a metering monitoring function.

Drying with a high-performance blower, a HEPA filter in the drying circuit is not required. The suction of drying air from the production room including filtering under clean room grade D. Discharge of drying air via the roof.Condensate drainage in the venting line to prevent backflow contamination


Materials: washing compartment and inner face of door: 316L. Cladding material: 1.4301. The materials used for seals and tubes must correspond with the recommendations of the US Food and Drug Administration (FDA). Works certificates for the above materials must be included in the delivery.


Freely programmable control (microprocessor control or PLC). The program should be structured in a modular fashion. Headings for the individual program modules must be provided.

Plain text displayed in the relevant language

Display of washing program, current program step, the temperature of the washing compartment, and remaining running time.

It must be possible to print out the programs and all their parameters (if required, printer to be connected).

Self-diagnosis, program, and malfunction statistics

The control should incorporate a memory that accommodates several (>10) wash programs that may be called up individually.

The machine must stop if the preset parameters are not complied with. The operator should then be provided with the reason why the process was canceled. When the machine is restarted, the entire wash program must be repeated.

Process monitoring

Monitoring of the following process parameters with display option and limit value monitoring with alarm or machine stop.

  • Temperature of rinsing water
  • Pump pressure (circulatory pump)
  • Drying temperature

The sensors must be readily accessible and removable for calibration purposes (cable length) and it must be possible to calibrate these with the entire measurement chain.

  • Dosage monitoring of detergent pumps
  • Sampling tap for water samples
  • Error display for important functions and utilities

A connection that enables the machine to be regularly requalified must be provided. For example, a connection that can be used to log the progress of the relevant parameters during a rinsing cycle via an on-site chart recorder.

Supply of energy and utilities

Connections for the following water types: purified water, 65 °C, connection to loop provided by installation location; drinking water both warm and cold.

  • Drainage via open funnel siphon to prevent backflow contamination
  • Electrical connection: 400 V/50 Hz
  • Steam connection
  • Connection to exhaust line provided by installation location
  • Constructional prerequisites

The equipment must be installed in a washroom. The particulate and microbiological loading of the room must correspond with clean room grade D. The nominal room temperature must be 20 °C +5/-2 °C, at 50% r.h.. Data on the required limits at the installation location (temperature, rel. humidity, electrostatic and magnetic influencing parameters) must be supplied.

  • Installation, start-up, and acceptance tests
  • The scope of delivery includes:
  • Free delivery and placing at the site (supervision of placing as a minimum)
  • Complete assembly and start-up test operation
  • Instruction of operating personnel

Necessary acceptance tests: the contract giver reserves the right to audit the manufacturing, programming, and quality assurance at the premises of the contract acceptor.

The “pre-delivery check”, otherwise known as the Factory Acceptance Test (FAT), at the manufacturer’s premises, guarantees the necessary manufacturing quality and ensures that the function tests are carried out.

The final acceptance, otherwise known as the Site Acceptance Test (SAT), by the contract giver, takes place at the installation location once assembly and start-up have been completed and the operating personnel have been instructed. It must be verified that the delivery of the facility is complete and correct, the documentation is complete, the installation is correct, the cleaning and auxiliary programs specified by the operator and also the safety devices are functioning faultlessly, and the locks and alarms are functioning faultlessly, the installation and function of the measuring equipment are correct and the initial calibration of the sensors was carried out at the installation location (if carried out by contract acceptor).

The basis for the pre-delivery check and the site acceptance test is a reference program to be compiled by the supplier according to the specifications of the contract acceptor containing all elements of the subsequent cleaning task. This program also serves as the basis for carrying out function tests within the scope of the operational qualification.

Furthermore, three cleaning cycles with contaminated equipment are to be carried out to assess the success of the acceptance test using the following criteria:

  • Visually clean / analytically clean
  • Visually dry
  • Surface quality of the materials washed
  • Analysis of the cleansing agent residues
  • Documentation, validation, qualification

The technical documentation to be supplied to qualify the facility can be found in the basic documents table. (see figure 3, figure 4, figure 5).

Installation qualification

The basic structuring and detailed description of an installation qualification are not dealt with here. This information can be found in the chapter entitled Qualification. (See chapter chapter 6 Qualification.) Only the measures that must be carried out (partly using forms) during the installation qualification are listed below, using fluid bed equipment as an example.

Technical documentation

To complete the technical documentation, documents concerning the facility or its components must be available. These are required for the installation, operation, and maintenance of the facility and must be checked as part of the installation qualification and documented in the form.

Operating procedures (SOPs)

The procedures required to operate the facility or its components must be checked (e.g. calibration, operating, maintenance, and cleaning procedures). Attention must be paid to the personnel training documentation. The form confirms that the check has been carried out.

The facility and its operating functions are assessed and tested during the risk analysis. Critical areas during operation, possible errors, and causes of the various risks, as well as the steps that must be taken to minimize the risks, must be defined and recorded. The completed risk analysis must be included alongside the IQ report. (See chapter 6.B.6 Risk analysis.)

Facility components

The technical data of the facility or its components is to be checked against the functional specification and documented in the form. The available ID numbers of the individual facility components are registered during this check.


The electrical circuit diagram must be used to check whether the wiring of the facility’s components is correct. A random check is sufficient. The circuits to be checked are specified in the form. If no deviations from the manufacturer’s documentation are found during the check, the circuit diagram may be accepted. Where deviations are found, the circuit diagram must be reviewed. The results must be documented in the form.

Hardware installation

The system hardware must be checked by inspecting the hardware configuration, the wiring, and the electrical supply. The results are documented in the form.

Checks must be carried out to verify that the control has been correctly connected to the functional modules and facility sensors, and this must be documented. If the manufacturer delivers an I/O list, a random check on 15 % of I/Os will suffice. If no deviations from the manufacturer’s documentation are found during the check, the list may be accepted. If deviations are found, all I/Os must be checked. The results must be documented in the form.

Software installation

The software installation must be documented. The designation, type, name, and version number (date) of the software must be noted. Similarly, the manufacturer and/or developer and the backup system must be recorded. The results are documented in the form.

Once the installation has been completed for the first time, facilities or their components must be thoroughly cleaned by the relevant operating procedures, and confirmation provided to show that this has been carried out.

Inspection of utility connections

The connected loads of all utilities to and from the facility must be compared with the manufacturer’s data. The connections must also be checked to make sure that they have been carried out correctly. The results must be documented in the form.

A list of the safety devices and locks included with the facility or its components must be compiled concerning the manufacturer’s specifications. When qualifying the installation, checks must be carried out and documented to verify that all facilities are available. The actual function of the facilities is checked within the scope of the operational qualification. The results of the installation qualification are documented in the form.

Emergency off button, Operator control panel, The facility halts operation as soon as the button is pressed. All motors and pumps are switched off and the valves for media supply are no longer supplied with electricity.

Construction and assembly materials

Materials used in the facilities or any of their components that come into contact with raw materials, intermediate or final products, must be listed in the form.

Spray device: stainless steel,

product contact parts: stainless steel

Filter list

A list of the filters required for the operation of the facility must be compiled. For sterile filters, copies of the test reports and the SOP used for implementation are also required. The filters are listed on the form.

Measuring and control points (M&C points)

A list must be compiled of the available M&C points that include the numbers of M&C points, the relevant manufacturer, the date of the last calibration, and the recalibration interval. The documentation of the last calibration must be included with the IQ report.

IQ – site acceptance test

A summary of the results obtained during the installation check is presented in the IQ site acceptance test. The results are checked using the form.

Technical documents are complete:

The facility supplied is checked to verify completeness and compliance with the technical specifications (incl. safety features and equipment).

The facility supplied is assembled and connected correctly.

The hardware and software for the automated system have been compiled, documented, and installed correctly.

The required operating procedures are available: cleaning, operation, and maintenance.

A log book template has been compiled.

Initial cleaning has been carried out.

All deficiencies have been rectified.

The initial start-up has been successfully carried out.

Deficiency report:

Deviations identified during the installation qualification must be documented in the deficiency report. The operator defines the measures required to rectify the deficiencies or deviations; names the departments or persons responsible; specifies deadlines by which the deficiency must be rectified at the latest; and authorizes implementation of the measures. Rectification of the deficiencies found must be documented in the form.

It must be ensured that changes made, as a result of rectifying deficiencies that have been determined, are assessed and documented per the established change control procedures, and also ensured that a requalification is carried out as required. The regulations governing requalification are laid down in the relevant operating procedures.

Operational qualification

The basic structuring and detailed description of an operational qualification are not dealt with here. This information may be found in the chapter entitled Qualification (see chapter chapter 6 Qualification). Only the measures that must be carried out (partly using forms) during the operational qualification are listed below using fluid bed equipment for illustration purposes.

Testing equipment required for qualification

The testing equipment required to carry out the operational qualification (OQ) must be listed. It must be ensured that calibration can be traced back to the standards of the NIST (National Institute of Standards and Technology) or equivalent organizations. It must be checked that the time interval before recalibration has not been exceeded. Copies of the documents from the last calibration of the testing equipment used must be included with the equipment/qualification documents.


The quality-relevant MC points (measuring and control points) have been named. A copy of the compiled list can be found in the installation qualification report. The measuring circuits must be calibrated before the operational qualification is carried out. A copy of the calibration report is filed with the OQ report. (See chapter 4.G Calibration.)


All alarms that respond to malfunctions in the facility must be checked by simulating the appropriate malfunctions. The type of simulation must be described in the form and documented. Care must be taken to ensure that only authorized personnel carry out these simulations.

Safety devices/locks

All safety devices in the facility must be checked to make sure that they are functioning correctly. “Safety devices” means all equipment that protects the operator from personal injury and the facility from improper handling. The tests must be documented with the aid of the form.

The facility halts operation as soon as the button is pressed. All motors and pumps are switched off and the valves for media supply are no longer supplied with electricity.

Press the emergency off button when the facility is in operation:

All motors stop moving

The valves for the utility supply are closed.

Flow rate test

The facility started with a flow rate of 1000 mі/h without heating output and product (this corresponds with the minimum capacity). The air velocity is measured and recorded at three different measuring points. This measurement is then repeated with a flow rate of 3500 mі/h and 6000 mі/h. The values determined at the various measuring points are compared with one another and assessed. The analysis is documented using a form.

Flow rate control

A check must be carried out to verify that the flow rate is being controlled correctly using three different flow rates. This involves starting the facility with a flow rate of 1000 m3/h without heating output and product. This setting is maintained for 15 minutes. The flow rate is then increased to 3500 m3/h for a further 15 minutes and then finally to 6000 m3/h for 15 minutes. During this time the control must maintain a stable value that falls within the specified range. The tolerance values are specified in a form where the results are also documented.

Spray rate

The facility is to be prepared as if a product cycle was about to be carried out, it is started with a flow rate of 2000 m3/h without heating and product. The spray medium to be used is water. Measurements are carried out for 10 minutes with the minimum, 50 %, and maximum spray rates respectively. The spray quantity is determined by establishing the tare weight. The trial must be carried out three times for each spray rate which must not deviate by more than ±5 %. The tests are documented in the form.

Heat distribution

To check the heat distribution, the facility must be prepared as if a product cycle was about to be carried out and must be started with a flow rate of 3000 m3/h without a product load. The temperature is set at 50 °C. Following a five-minute warm-up phase, the temperature is measured at 5 different points above the sieve screen for 10 minutes. None of the measured values may deviate by more than ±5 °C from the average value determined above the screen. The trial is repeated at 80 °C and 110 °C. The tests are documented in a form.

Temperature control

The temperature control is checked without a product with a flow rate of 5000 m3/h, at 50 °C, 80 °C, and 110 °C respectively. After the five-minute warm-up phase, the temperature must settle down to a constant level which is maintained for 10 minutes. The same procedure is then carried out for temperatures of 80 °C and 110 °C respectively and the control checked. The deviations must not be more than ±5 °C from the preset value. The results must be documented. A printout of the plot must be included with the OQ report.

Screen masks

Checks must be carried out to verify whether the screen masks perform the functions they have been assigned. It must be ensured that the operational parameters can be modified within their assigned limits. It must be possible to store new formulations with the programmed operational parameters and call these up again. The temperature, humidity, and pressure values displayed are checked during calibration. A hard copy of each screen mask must be made and included with the form.

Equipment functions

This involves testing specific functions of the facility such as the “on/off” or “raise/lower” operator control elements. The decision as to which tests should be carried out is influenced by insights gained from the risk analysis. The tests are documented in a form.

Product cycle

To check the entire sequence of functions in context, a trial run is carried out with the product. The manufacturing instructions for the product must be used as the basis for the trial run.

The product cycle was implemented by the manufacturing instructions.

It was possible to implement the product cycle without interruption.

The prescription steps were processed correctly.

The step-enabling conditions were achieved and identified.

No process-related malfunctions occurred.

The preset process parameters were complied with.

The product was checked under existing guidelines and corresponds with the specifications.

The final product is checked by the relevant test procedure. The implementation and the test results must be documented. The product cycle data may be used for performance qualification and validation.

Batch record

The recording of a batch starts when the process begins and ends when the container is lowered. It must be ensured that the process data entered and the measured values gathered are reproduced correctly in the batch record. To check this, the batch record for the test run described above must be recorded manually in the form. Once the trial has ended, the batch record which is generated automatically is compared with the manually recorded data. There must be no deviations.

Data backup

Checks must be carried out to determine how the system responds in the event of a power/utilities failure. It must be ensured that the operating data that has accumulated up to this point is not lost in the event of a sudden power/utilities failure. The facility must also be capable of continuing with the last process status following the restoration of the power/utilities and final confirmation. There must be no deviations in the parameters set or the process data. The test is documented using the form.

Access protection

It must be demonstrated that unauthorized individuals cannot access the system and manipulate data. A check must be carried out to determine whether operational parameters can only be modified by authorized personnel. The analysis is documented using the form.

Deficiency report

Deviations identified during the operational qualification must be documented in the deficiency report. The operator defines the measures required to rectify the deficiencies or deviations; names the departments and/or persons responsible; specifies deadlines by which the deficiency must be rectified at the latest and authorizes implementation of the measures. Rectification of the deficiencies identified must be documented.

It must be ensured that changes made, as a result of rectifying deficiencies that have been determined, are assessed and documented per the established change control procedures, and a requalification is carried out as required.

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About Pharmaceutical Guidanace

Ms. Abha Maurya is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 18 years of rich experience in pharmaceutical field. During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube

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