Concept of URS,DQ, IQ, OQ, PQ in Pharma

Concept of URS,DQ,IQ,OQ,PQ in Pharma

Introduction

Validation

User Requirement Specification.(URS)

Phase of validation

Design qualification (DQ)

Installation Qualification (IQ)

Operation Qualification (OQ)

Performance Qualification (PQ)

Maintenance Qualification (MQ)

Component Qualification (CQ)

Instrument Re-Qualification

According to the Food and Drug Administration (FDA), the goal of validation is to: “Establish documented evidence which

provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined

specifications and quality attributes.”

It is a requirement for Good Manufacturing Practices and other regulatory requirements.

What does this mean? An quantitative approach is needed to prove quality, functionality, and performance of a

pharmaceutical/biotechnological manufacturing process.

This approach will be applied to individual pieces of equipment as well as the manufacturi
manufacturing
ng process as a whole. Guidelines

for validation are set by the FDA, but the specifications of validation are determined by the pharmaceutical/biotech

company.

User Requirements Specification (URS), is the most critical of documents and yet, the most often bungled. Whether the

system is purely mechanical, or a mix of electro

electro-mechanical,
mechanical, or solely a software program, the successful compilation and

execution of the Installation Qualification (IQ) (for installation), Operational Qualification (OQ) (for functionality) and the

Performance / Product Qualification (PQ) (for operability), is dependent on an User Requirements Specification (URS)

containing clear, concise and

nd testable requirements.

Once the end user requirements specification is documented, agreed and approved they form the basic

URS Level-11 document. The engineers (or vendor) can then commence the preliminary design to establish
exactly what functions are required for each of the items specified in the user requirements specification, the end user

has listed. Once this functionality is documented and approved it forms URS Level
Level-22 document. This is the final level

of the URS unless software is used. If software is to be used, the URS Level
Level-22 document, is passed to the code writers.

As the code is written, lines, or groups of lines, of code must be attributed to the individual functions that necessitate

their presence. The completion of this task results in the completion of the URS Level
Level-33 document

Developing the URS to this level is unique in most industries, but is, standard practice in strictly regulated industries,

as it is a major building block in the creation of quality software. The URS Level
Level-33 document, contains all the

traceability which is deemed mandatory for software assessed to be critical to product quality, in the pharmaceutical

regulated industries.

The URS can contain a large number of requirements and should therefore be structured in a way that will permit easy

access to information.
on. The requirement specification must be formally reviewed and approved by the pharmaceutical

manufacturer.

The following guidelines should be followed during the production of the URS :

1. Each requirement statement to be uniquely referenced,and no longer than 250 words.

2. Requirement statements should not be duplicated nor contradicted.

3. The URS should express requirements and not design solutions.

4. Each requirement should be testable.

5. The URS must be understood by both user and supplier; ambiguity and jargon should be avoided.

6. The use of diagrams is often useful.

7. The scope for readers to make assumptions or misinterpret should be minimized.

8. Wherever possible, the URS should distingui

distinguish
sh between mandatory/regulatory requirements and desirable

features.

The URS for a GMP computer control system application will typically address the following: Scope of system

supply

Objectives

Regulatory requirements

Process overview

System boundaries

Operational considerations

Manufacturing design data

 Instrument application data

Data records

System functions

System software

System hardware and peripherals

System interfaces Environmental conditions Access security Diagnostics System availability Safety Test and calibration

Quality procedures Software development life cycle Documentation requirements Training

Engineering/installation standards Ongoing support Warranty Delivery/commercial requirements

Newly sanctioned systems will require compliance with regulations for GMP electronic records and electronic

signatures, and definition of the functionality required will need to be included. The structure of the URS be used as

the basis for the presentation format of the FDS and hardware and software design specifications; this helps ensure

design decisions are auditable back to the source requirement. Once reviewed and approved internally, the URS is

issued to prospective
ospective suppliers as part of the tender document set so that detailed quotations for the system application

can be obtained.

URS provides the following key benefits for the validation program:

1. Clarifies technical, quality, and documentation requirements to the vendor( s).

2. Enables the pharmaceutical manufacturer to assess the technical, regulatory, and commercial compliance

(or otherwise) of submitted bids against a formal specification.

3. Ensures the basis of a structured approach to the presentation of information.

4. Provides a basis for testing and test acceptance criteria.

5. Provide a baseline for validation and verification..

They must be comprehensive. Each and every requirement relating to product safety, identity, strength, purity, and

quality must be identified. Hence, Quality Assurance (QA) must have a significant role in reviewing and approving

the final set of requirements,

ts, and must be an approver of changes to any requirement that can affect the above

product or process attributes (e.g., cGMP’s).

Given a comprehensive User Requirements Specification that has been approved by QA and is under project

change management, the Design Qualification(DQ) process then can be reduced to two key objectives:

Documented verification that the overall

erall design appears to address, by some means, each and every requirement

affecting the product and performance of the manufacturing process (or, in the case of uunknown
nknown product or multi-
multi

product manufacturing facility,

acility, the required equipment system performance
mance capabilities).
 Identification (and documentation) of the critical individual physical components, attributes, and operational features

that directly support meeting each requirement.

Validation is broken down into 5 main phases,

Design qualification (DQ)

Installation qualification (IQ)

Operational qualification (OQ)

Performance qualification (PQ)

Maintenance Qualification (MQ)

Component qualification (CQ)

Vendor’s Site Owner’s site Before Purchase Before Use After Use Structurally Validated Products DQ Functional

Validation Installation Operational Performance Qualification Maintenance OQ, PQ,IQ, OQ, PQ System Suitability

During Use

Validation: Refers to the total life cycle of a product from development through use and maintenance.

Owners are responsible for Validating Their Processes (personnel, equipment, methods, SOPs) to ensure compliance to

cGMP/GLP regulations.

Qualification: (Inspection, functional testing and documentation review)

Is a part of the validation process which verifies module and system functional performance prior to being placed on
on-

line and thereafter according to a standard operating procedure.

It is a basic requirement of good analytical chemistry that balances and other analytical instruments must be suitable for

the purpose for which they are used and that they must be appropriately calibrated. As a consequence, Equipment

Qualification is gaining
ning more and more importance in ensuring the validity of results. Regulatory bodies also seem to be

turning their attention increasingly to this area, and manufacturers of analytical equipment are forced to play a significant

role in the various steps of Equipment Qualification.

Step 1: Design Qualification (DQ) defines the functional and operational specifications of a balance or instrument.

Step 2 :Installation Qualification (IQ) ensures that a balance or instrument is received as designed and specified. It

documents the installation in the selected user environment.

Step 3: Operational Qualification (OQ) demonstrates that a balance or instr

instrument
ument will function according to its

operational specification in the selected environment.

Step 4: Performance Qualification (PQ) demonstrates that a balance or instrument consistently performs according to

a specification appropriate to its routine use.

Step 5: Maintenance Qualification (MQ) describes and documents any maintenance required on the equipment
.

Design qualification (DQ) is the process of completing and documenting design reviews to illustrate that all quality

aspects have been fully considered at the design stage. The purpose is to ensure that all the requirements for the final

systems have been clearly defined at the sta

start.
rt. Design Qualification (DQ) defines the functional and operational

specifications of the instrument and details the conscious decisions made in the selection of the supplier. DQ should

ensure that instruments have all the necessary functions and performa
performance
nce criteria that will enable them to be successfully

implemented for the intended application and to meet user requirements.

The list below shows the recommended steps that should be considered for inclusion in a Design

Qualification.

– Description of the analysis problem

– Description of the intended use for the equipment

– Description of the intended environment

– Preliminary selection of the functional and performance specifications (technical, environmental, safety)

– Preliminary selection of the supplier

– Final selection of the supplier and equipment

– Development and documentation of final functional and operational specifications

As part of the design qualification process, the vendor should be qualified; the question is how should this be done? Is an

established and documented quality system enough (e.g. ISO 9001), or should there be a direct audit? The answer is that

there may be situations where a vendor audit is recommended: for example, when complex computer systems are being

developed for a specific user. However, this is rarely the case for balances and analytical instruments. If equipment does

not include a computer system, a good reputation, one’s own experience or good references from other users – together

with ISO 9001 certification - can be sufficient.

Installation qualification (IQ) is the process of checking the installation, to ensure that the components meet the

approved specification and are installed correctly, and to see how that information is recorded. The purpose is to ensure

that all aspects (static attributes) of the facili

facility
ty or equipment are installed correctly and comply with the original design.

all of the instrumentation components are identified and checked against the manufacturer’s component listing. The

working environment conditions are documented and checked to ens

ensure
ure that they are suitable for the operation of the

instrument.
 Installation Qualification establishes that the instrument is received as designed and specified, that it is properly installed

in the selected environment, and that this environment is su

suitable
itable for the operation and use of the instrument. Before

installation: – Obtain manufacturer’s recommendations for installation site requirements. – Check the site for the

fulfillment of the manufacturer’s recommendations (utilities such as electricity, water and gases plus environmental

conditions such as humidity, temperature, vibration level and dust). – Allow sufficient shelf space for the equipment itself,

related SOPs, operating manuals, logbooks and software.

Operational qualification (OQ) is the process of testing to ensure that the individual and combined systems function

to meet agreed performance criteria and to check how the result of testing is recorded. The purpose is to ensure that

all the dynamic attributes comply with the original design. Each of the instrument’s function are checked to ensure

that they conform to the manufacturer’s specifications. This includes the use of certified, traceable electrical

simulators and standards to verify that the equipment is processing input signa
signals correctly.

Performance qualification (PQ), also called process qualification, is the process of testing to ensure that the individual

and combined systems function to meet agreed performance criteria on a consistent basis and to check how the result of

testing is recorded. The purpose is to ensure that the criteria specified can be achieved on a reliable basis over a period of

time. The performance of the equipment for its routine analytical use is checked to ensure that this complies with its

specification. The temperature sensor readings are compa

compared
red with a certified reference thermometer. After calibration, the

conductivity sensor readings are compared using certified, traceable control standards.

Control Standards of similar values to the intended test samples must be used for PQ. Performance Qu
Qualification (PQ) is

the process of demonstrating that an instrument consistently performs according to a specification appropriate to its

routine use. Important here is the word consistently. The test frequency is much higher than for OQ. Another differenc
difference is

that PQ should always be performed under conditions that are similar to routine sample analysis.

PQ should be performed on a daily (or at least a weekly) basis, or whenever the instrument is used. The test frequency

depends not only on the stability of the equipment but also on everything in the system that may contribute to the

analysis results.

1. Define the performance criteria and test procedures.

2. Select critical parameters.

3. Define the test intervals.

The MQ describes and documents any maintenance required on the equipment. This includes routine servicing and

any repairs necessary. Details of any maintenance contracts are also documented in this
section, together with a list of authorized service engin
engineers.
eers. In addition, the MQ includes the routine cleaning of

the equipment and also its ultimate disposal.

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

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 manufa
manufacturer.

Instrument Validation should not be viewed as a one

one-off event – confidence in analytical results is required for the whole

of the instrument’s working life.

To ensure that this confidence is retained, the instrument validation process should be repeated at regular intervals

during the instruments operational life.

The difference between Installation Validation and Re

Re- Qualification is that IQ is omitted for the
th Re-

Qualification.

Re-Qualification
Qualification should be performed at least annually and should be performed more frequently for applications

whose test results have critical implications