DOYEN MEDIPHARM LTD
Member of Doyen Group PLC
Validation Plan
Doyen Medipharm Ltd. have been contracted to design and manufacture a machine to pack various product reference for customer order number XXXX ,dated XXXX and received by Doyen on XXXX .
The packages are to be terminally sterilised and the machine is to be validated to ensure it produces products of specified integrity.
This document is the validation plan for the generation and implementation of an overall validation procedure to cover the design, manufacture, and installation of the machine at customer plant in XXXX. The scope of Doyen’s activities in validation shall be up to and including installation qualification and performance qualification. Process qualification (i.e. the act of proving the materials produce products to standard ) or process optimisation are not covered by these documents.
Validation Concept
The validation envisaged by this document will generally follow the validation features of the GAMP 4 guidelines but will address only the elements affected by the regulatory environment. The procedure utilised in the validation process is shown on the attached flow chart Appendix 1. The risk analysis shown in the flow chart will be used to determine those elements of the design that impact pack integrity and thus are affected by mandatory regulations. The term risk analysis, throughout this and related documents, relates only to the assessment of risks that impact product integrity and are not concerned with general functionality. Tests on all elements of the machine (including mechanical, electrical and software) will be designed to challenge risks identified in the analysis.
The validation process will comprise four essential elements :-
- Design verification - mechanical, electrical and software.
- Risk analysis to determine those elements of the design that may impact on product integrity.
The risk analysis approach uses a “double redundancy” approach, ie any single event that may cause a faulty product = fault (probable risk) Any 2 events that may together may cause a faulty product = fault (highly improbable risk). Therefore by implementing dual redundancy on controls the probable risks can be eliminated.
The Risk analysis approach gives the following results when each risk is identified and addressed.
- No Risk to product
- Risk that can be tested to prove fail safe operation
- Risk that cannot be tested – Requires re-design
- Risk that can be tested, however requires regular checks of system, or human intervention in a controlled manner – Standard operating procedure (SOP)
- Modification of the design where the risk can be eliminated or automatically monitored within the machines own control system.
- The construction of a series of tests to challenge the potential risks that have been identified.
The design verification process will ensure that the machine complies with product critical parts of the user requirement specification. Changes in design will be recorded in all engineering disciplines to provide an audit trail of design decisions and ensure the reasons for changes are clear. During the design process a document titled ‘Hardware Conformance’ will be produced to substantiate component choice and robustness of the design. Flowcharts will be used during software design to facilitate understanding of the logic and will form the basis of design evaluation and risk analysis.
The documented risk analysis of each potential failure mode for each machine element or discipline will be included in the validation document file. The risk analysis will be based upon the specification, hardware specified, mechanical drawings, and the electrical and software elements of the machine. The tests to challenge risks will be cross-referenced with each risk element. Tests will specify expected results or acceptance criteria for each test or part of test. Where risks are identified that are operator or maintenance related , mandatory operating and maintenance procedures will be documented. The software risk analysis will embrace the guidelines covered in 21CFR part 11, and suitable testing will be carried out to substantiate compliance of electronic records and data.
Each test will be conducted in accordance with an overall protocol for the range of tests or the instructions on the test sheet. The results are to be recorded on relevant test sheets. In the event that any test fails, the failure mode will be noted on the test sheet and the test sheet will remain in the overall test programme. Details of re-tests and any changes are to be included on the failure sheet for cross-reference purposes.
Design Modularisation
Where practical and possible, the machine design will be constructed on a modular basis. Where such modules exist, and simple measurable interfaces exist between the modules, only the module and its’ interface with other modules need be re-appraised and if necessary revalidated in the event of a change within the module.
User Definable Controls and Recording of Critical Machine Features
The status or accuracy of user definable features (such as temperature) and the condition of critical change parts will be recorded using measuring devices that have current calibration certificates to National standards. Engine divided steel rules will not require calibration certificates.
Factory Acceptance Tests
Validation tests and completion of validation documentation are part of factory acceptance. Additional factory acceptance tests will be constructed to challenge the machine functionality and compliance with specification. Such additional tests that are not designed to challenge product critical features will not be included in the validation file. Factory acceptance tests will include some provisional Process Optimisation. Such optimisation will be informal and not part of the validation procedure.
Testing is carried out as follows:
- Installation Qualification (IQ) is carried out by use of Doyen “tick list” approach, and is completed at Doyen’s premises prior to OQ testing.
- Operational Qualification (OQ) is carried out using the test protocols developed from the Risk analysis approach. These tests are completed at Doyen’s premises and are then repeated following installation on the customers site. A facility is provided for the customer to witness and sign as approved each OQ test once completed. The customer will use his own discretion with regard to approval of these tests.(Note it is not a Doyen requirement that the customer sign off the completed tests as approved, this is purely as an aid to the customer, should he wish to include the Doyen documentation within his overall validation package)
- Performance Qualification (Optimisation) Doyen may, where contracted carry out informal optimisation works. However formal documented optimisation cannot be completed by Doyen at Doyen’s works, as control of goods in, environmental and SOP working practices cannot be maintained outside of the customers control and clean room environment.
Machine Installation Qualification
All tests conducted during the validation part of machine acceptance will be re-conducted to satisfy Installation Qualification requirements and to demonstrate no degradation of machine performance has occurred during shipment. This testing will be an exact duplication of the OQ testing carried out prior to machine acceptance at Doyen.
Documentary Controls.
All validation documents will be controlled by Doyen Medipharm and a master validation file will be kept in Doyen premises in Cambridge, England. All documents issued by Doyen will contain issue numbers and date of issue. A master index is maintained showing current date of each issue and issue number of all documents. For any changes, italics will be used in documents to denote changes between issues. Facility for Customers to approve changes will be included in the change documents but does not imply Customers must sign all change documents.
Document and test approval
The approval procedures and responsibilities are detailed in document No.VAL-4SS- XXXX-2
Validation timetable
No specific timetable will be defined for validation activities, but:-
-
Design work will not commence until the validation plan, quality plan and functional specification have been produced.
-
Validation documentation will be generated throughout the project.
-
Designs will not be finalised until completion of the risk analysis.
-
No tests will be conducted until the full test programme has been approved.
The objective of the validation documents are to :-
-
Provide full documentary evidence that mechanical, electrical and software design of the machine is robust and will produce products of the specified integrity.
-
Enable the machine leaving the works to be accompanied with a full record of tests conducted showing the results of those tests.
-
Ensure initial set-up of user definable elements and critical change features are recorded to enable repeatability of the set-up conditions throughout the machines’ life.
-
Provide the basis of generation of mandatory operating procedures necessary to ensure the maintenance of pack integrity.
-
Enable the generation of mandatory planned maintenance procedures necessary to ensure pack integrity.
f) Provide a documentary source of evidence should any regulatory body wish to satisfy themselves that design and manufacturing procedures to ensure pack integrity have been followed.
Approved
------------------------- |
------------------------- |
Doyen Medipharm |
customer . |
Date
------------------------- |
------------------------- |
|
