Управление бизнесом
Маркетин
R&D
GLP
GCP
Проектирование (GEP)


GMP по разделам:
Персонал

Документация

Контроль качества
Аутсорсинговая деятельность
Самоинспекция
Логистика
GSP
GDP
GAMP
GPP
GACP
Терминология GMP
Экологический менеджмент
Forum
Ссылки
О проекте

Для содержимого этой страницы требуется более новая версия Adobe Flash Player.

Получить проигрыватель Adobe Flash Player




6.H Special cases of qualification

Here you will find answers to the following questions:

  • What is understood by the term "retrospective qualification"?
  • When must "requalification" be carried out?
  • What is a "review"?
  • How is the "qualified status" of a facility sustained?
  • What needs to be noted when qualifying simple equipment?

6.H.1 Retrospective qualification

The term "retrospective qualification" is usually used for qualification of equipment that is already available and in operation. The aim of retrospective qualification is to compile current technical and pharmaceutical documentation that is as complete as possible.

For the qualification of an existing facility/equipment, risk analysis is very helpful as it makes it possible to limit the scope of testing of the qualification. It offers the possibility of reducing the extent of the test, e.g. though existing operating experiences. Moreover, the risk analysis leads to in-depth scrutiny of the process and equipment. Existing GMP deficits can be addressed and evaluated.

By definition, installation qualification (IQ) cannot be carried out here, as the facility has already been assembled and connected. As a minimum requirement for the IQ, the documentation specified in figure 6.H-1 should be available in the latest version or should be brought to the latest version by means of a review. Any deviations that are ascertained must be evaluated.

Figure 6.H-1 Minimum requirements for the scope of documentation for retrospective qualification

Minimum requirements for the scope of documentation for retrospective qualification

  • User requirements with corresponding work conditions and critical limits (risk analysis!) for the equipment
  • R & I plans, facility plans, construction drawings
  • List of measuring and control points (M&C list) including quality relevant measuring points
  • Hardware and software documentation
  • Procedures for calibration and maintenance
  • Results of calibration and maintenance (if available)
  • Equipment log
  • Cleaning procedures
  • Operating procedures
  • Proof of staff training

Retrospective qualification is usually spoken of if an evaluation of various records (e.g. logs, minutes, deviation reports, change control documentation, entries in the production's record) is used for qualification in terms of the OQ.

Increasingly, retrospective qualification as defined above is not acceptable. The aim should be to carry out OQ with the minimum requirements of tests specified in figure 6.H-2.

Figure 6.H-2 Minimum requirements for the scope of OQ for retrospective qualification

Minimum requirements for the scope of OQ for retrospective qualification

  • Alarm and fault reports
  • Function control plans
  • Selected functions from risk analysis
  • CIP/SIP/DIP functionalities
  • Checking of change controls
  • Evaluation of deviations
  • User administration (if available)

6.H.2 Requalification

The term requalification covers several aspects. This can be the regular requalification of facilities, requalification of an already qualified facility after significant changes and maintenance of the qualified status.

Every company should have a policy of how to deal with this issue, e.g. in the validation master plan.

Various approaches are feasible for this company policy.

  • in the form of a review every three years, with evaluation of the changes made, deviations, etc. and as a result, a derivation of the requalification
  • general requalification after a period of time x
  • general requalification after a certain number of changes
  • general requalification only after significant changes
    (the term significant must be defined.)

Relevant changes to qualified equipment involve requalification. Whether or not the changes are relevant must be decided based on a risk analysis. In the process, the extent to which the change exerts an influence on the product quality must be taken into consideration. Depending on the evaluation, the planned changes must be evaluated and documented as part of a change control procedure.

The scope of a requalification is established via a risk analysis, the change control documentation and the deviation documentation. The basic procedure for requalification is the same as that for initial qualification. It must be ensured that any ascertained deviations from proper operation of a facility trigger a deviation during requalification.

6.H.3 Content of a review

Irrespective of the execution of required requalification measures, the qualification can be reviewed and evaluated in the form of a review in order to prepare inspections/audits or to adapt the qualification to the state-of-the-art.

The aim of a review is to ascertain whether or not the equipment is still in a qualified status. Figure 6.H.2 shows a summary of the content.

Figure 6.H-3 Contents of a review

Contents of a review

  • Calibration
  • Maintenance measures
  • Log book
  • Deviations
  • Changes
  • Risk analysis
  • Qualification documentation

In addition, the review is a good way to check the implementation of the quality assurance system. Any deviations found always lead to a deviation and review of the impact on the product.

Calibration

During the review, a check is carried out to see if the calibration is carried out regularly in accordance with the prescribed calibration interval.

Special attention must be paid to whether or not warning and/or tolerance limits have been exceeded, or whether or not trends can be recognised. From this review, it may be possible to derive changes to the calibration interval or warning and tolerance limits (see also chapter 4.G Calibration).

Maintenance measures

This review chapter deals with the servicing and maintenance reports and evaluates them in terms of the possible impacts on the qualification status.

Servicing must have been carried out regularly according to the defined servicing type. Attention must be paid to trends, e.g. frequent occurrence of certain defects. If relevant, changes to the servicing interval may be derived from this review (see also chapter 4.H Maintenance).

Log book

The documentation of the log book is checked in terms of technical problems and trends.

Any technical deficiencies observed must have previously led to adequate measures (see also chapter 4 Log book).

Deviations

The deviation reports on the operation of the equipment are evaluated in terms of failure trends.

A possible influence of the deviations that occurred on the qualification status is assessed. The aim of this part of the review is to identify systematic failures.

Changes

While larger changes usually involve requalification measures directly during the change process, this can often be avoided for so-called "small" changes (e.g. the exchange of components of the same type during maintenance measures).

However, the total of several of these small changes over time can exert a significant influence on the overall system. During the review, series of small changes that have not lead to requalification are evaluated as a whole in terms of their influence on the qualification status.

Risk analysis

The risk analysis is discussed here again and reviewed if necessary.

This is carried out by the qualification team based on the operating experience that has been gained since the time of initial qualification, and on the basis of the findings from the issues dealt with during the review.

Qualification documentation

The available qualification documentation is checked to see if it corresponds to the current requirements (internal/external regulatory requirements, state of science and technology).

The extent to which the working area (ranges of the process parameters) within which the equipment is currently used may also have changed is also checked. A possibly revised risk analysis must be covered by the existing qualification, or test plans must be recompiled and implemented.

M&C points

It is checked if the measuring and control data sheets have to be updated or recompiled.

This is carried out based on the revised risk analysis (e.g. changed classification of M&C points) and the results from the "Calibration" review point (e.g. changed calibration interval).

Review documentation

To document the review, a review report is compiled which also contains all deviations or changes.

The activities carried out and their results are documented in the review report and compared with the acceptance criteria. The overall evaluation can conclude with the following results:

  • The equipment is now, as before, in a qualified status.
  • The equipment is placed in "qualification quarantine" status until the deviations/deficiencies ascertained are eliminated.

6.H.4 Maintenance of the qualified status

The qualified status of a facility is maintained via the change control procedure (CC). Every change requires qualification and is thus subject to the principles of qualification. The change is to be documented in the same way and the reference is to be made to the test plans from the initial qualification. The changes are to be formally checked for correct installation, documentation and operation. In addition, the CC application must describe and evaluate the risks of the change, the impacts and the interfaces to other components and functions. Which user requirements from the original qualification are affected by this change must be formally checked, and the required tests can then be deduced from the trace matrix. The tests from the risk assessment of the change are then added to this. The test protocols are released with the CC. The results are documented, reviewed and released promptly. They are enclosed with the facility documentation so that it always describes the current status of the facility (Life Cycle). This procedure can also be considered as requalification. In addition to the tests from the original qualification and risk assessment, accompanying measures, such as approval by the plant, cleaning, checking of the official documentation and impacts on the process validation, are usually also necessary.

Like-for-like exchange of equipment does not come under a formal change control procedure. Nonetheless, the exchange of this equipment must also be documented in the facility log book. In addition, the facility documentation must be adapted, as this data is required for failure analyses and maintenance strategies, and the releases by the plant are required. The facility status must be marked. The documentation must be maintained, as prescribed by Good Engineering Practice (GEP).

Figure 6.H-4 gives an example of tests for exchanging a valve (1:1) in a pipe:

Figure 6.H-4 Tests when exchanging a valve (1:1)

Type of test

Possible details of the test

Raw data

Comments

Test against specification

Material

Certificate
(e.g. 3.1.B)

 
 

Surface roughness

Measuring record

 
 

Seals
(conformity)

Certificate

 
 

Dimensions (geometry)

Test against drawing

 
 

Passivation

Certification

 

Adaptation of the documentation

Flow chart

Version
management

 
 

Isometries

Version management

 
 

Storage of the order

   

Labelling of the valve

Application and testing of the labelling

Flow chart

 

Function check

   

Depending on the function of the valve

Release by plant

     

Rinse documentation

Before and after installation of the valve

   

Documentation in the facility log book

     

6.H.5 Qualification of simple equipment

In the case of simple analysis or manufacturing equipment, which is not a computerised system and does not generate any electronic raw data, the proper mode of operation can be proven by an operational test. Examples of such equipment are balances and pH meters (see also chapter 13 Examples).

The reduced scope of qualification in this case can, for example, be documented in the corresponding equipment SOP. The SOP contains, amongst other things, the description of the operational test and is also the qualification plan. There is no need for a separate risk analysis. The equipment is to be set up and operated in accordance with the manufacturer's specifications. The equipment must, if necessary, be calibrated. Qualification is completed with the passed and documented first operational test. This is signed by the person responsible for validation and represents the qualification report. Requalification/review can be omitted as the functionality is proven through a regular operational test.

Figure 6.H-5 lists examples of equipment documents as part of qualification of simple equipment.

Figure 6.H-5 Content of the equipment documentation

Content of the equipment documentation

  • Order documents/investment call (corresponds to start of project)
  • Operating instructions/Manufacturer's instruction manual
  • Certificate of EMC test/EMC test protocol (if required)
  • List of responsible persons (e.g. person in charge of equipment, person in charge of validation)
  • M&C data sheet
  • List of trained employees (if required)
  • Maintenance schedule/report
  • Installation certification/equipment acceptance (optional)
  • Log book
  • Calibration reports/operational test reports/calibration instructions
  • Repair certification/service reports/conformity certification/CE certificates

Summary

Existing facility can be qualified retrospectively. Minimum requirements for retrospective qualification of equipment are described.

A qualification status once reached must be maintained over the entire life cycle through to decommissioning of the equipment. This is achieved via regular calibration, servicing and maintenance measures, regular testing (reviews) or a change control procedure, which can lead to renewed qualification (requalification) depending on the change in the equipment.

It may be the case that simple equipment can be qualified in a reduced scope which focuses on the operational qualification.


Рейтинг@Mail.ru Rambler's Top100