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Training workshop: Training workshop on regulatory requirements for registration of Artemisinin based combined medicines and assessment of data submitted to regulatory authorities, February 23-27, 2009, Kampala, Uganda.
Equipment
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Equipment
Objectives
To review the requirements for equipment selection design use Maintenance
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Validation
Objectives (2)
To discuss the principles of qualification of equipment, with specific focus on: The different stages of qualification Requalification and Qualification of in use equipment
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Equipment
Principle
Equipment must be located designed constructed adapted maintained to suit the operations to be carried out
13.1
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Equipment
Principles
Equipment layout and design must aim: to minimize risks of error to permit effective cleaning and maintenance To avoid: cross-contamination, dust and dirt build-up any adverse effect on the quality of products Equipment must be installed to: minimize risks of error minimize risks of contamination
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
13.1, 13.2
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Equipment
Balances and Measuring Equipment
Appropriate range and precision available In production and quality control Calibrated scheduled basis checks records maintained
13.5
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Equipment
Production equipment
Appropriate design easily and thoroughly cleaned on a scheduled basis procedures and records No hazard to the products contact parts of suitable non-reactive materials non additive and not absorptive Defective equipment removed, or labelled to prevent use
13.9, 13.10
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Equipment
Production equipment
Closed equipment used when possible Open equipment, or when equipment opened, precautions taken to prevent contamination Non-dedicated equipment cleaned according to validated cleaning procedures between different products Current drawings of critical equipment and support systems maintained
13.11 13.13
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Equipment
Control laboratory equipment
Equipment and instruments suitable for the tests to be performed Defective equipment removed labelled
13.7, 13.10
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Equipment
Washing, cleaning and drying
Equipment used for washing and drying not the source of contamination Equipment design should promote easy cleaning Cleaning on scheduled basis, procedures and records Washing and cleaning manual automated (Clean in place (CIP), Steam in place (SIP))
13.6, 13.8
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Equipment
Possible Issues
Poor design Lack of safety
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Validation
General
Qualification policy for systems and equipment To include instruments used in production and quality control
New systems and equipment: All stages of qualification applicable (DQ, IQ, OQ and PQ)
In some cases: Not all stages of qualification may be required e.g. electrical supply systems
3.1 3.4
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Validation
General
Qualification policy for systems and equipment To include instruments used in production and quality control
New systems and equipment: All stages of qualification applicable (DQ, IQ, OQ and PQ)
In some cases: Not all stages of qualification may be required e.g. electrical supply systems
3.1 3.4
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Validation
General (continued)
Qualification should be done in accordance with predetermined and approved qualification protocols
The results of the qualification should be recorded and reflected in qualification reports The extent of the qualification should be based on the criticality of a system or equipment, e.g. Blenders, autoclaves or computerized systems
3.10 3.11
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Validation
General (continued)
Qualification should be done in accordance with predetermined and approved qualification protocols
The results of the qualification should be recorded and reflected in qualification reports The extent of the qualification should be based on the criticality of a system or equipment, e.g. Blenders, autoclaves or computerized systems
3.10 3.11
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Glossary
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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- confirm compliance with specified requirements or criteria (Do you have the right tool for the job?)
- Performed on one element or component of the process to be validated - Conduct tests to establish if the component of a process has the attributes to produce a specified outcome. Validation - Proof. Document that the process will consistently produce a predetermined outcome.
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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
Validation
Stages of qualification
Design qualification
Installation qualification Operational qualification Performance qualification
3.11
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Validation
Stages of qualification
Design qualification
Installation qualification Operational qualification Performance qualification Change control
3.11.
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Validation
General
Systems: Qualified before equipment
Equipment: Qualified before routine use
Validation
Design qualification
User requirements should be considered when deciding on the specific design of a system or equipment A suitable supplier should be selected for the appropriate system or equipment (approved vendor)
4.1 4.2
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Validation
Installation qualification
Verifies that the correct equipment has been received and installed as per plan and protocol. Also that it is complete and undamaged (parts, services, controls, gauges and other components) - Normally advised to prepare requirements for calibration, maintenance and cleaning at this stage Verifies that equipment has been properly installed and calibrated including connections to utilities.
Calibrate the measuring, control and indicating devices against appropriate, traceable national or international standards
5.1 5.4
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Validation
Installation qualification (2)
Documented records for the installation installation qualification report
Indicate satisfactory installation Include details, e.g. The supplier and manufacturer System or equipment name, model and serial number Date of installation Spare parts, relevant procedures and certificates
5.5
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Validation
Operational qualification
Systems and equipment should operate correctly operation verified as in the qualification protocol Verifies that the equipment operates consistently within established limits and tolerances over the defined operating ranges. Studies on critical variable to include conditions encompassing upper and lower operating limits and circumstances (i.e. worst case conditions) Challenges equipment functionally to verify compliance with manufacturers specifications and end user defined requirements. To include verification of operation of all system elements, parts, services, controls, gauges and other components
6.1 6.3
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Validation
Operational qualification (2)
Documented records (Operational qualification report) Finalize and approve SOP (operation) Training of operators provided training records Systems and equipment released for routine use after completion of operational qualification, provided that: All calibration, cleaning, maintenance, training and related tests and results were found to be acceptable
6.4 6.7
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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How may runs are to be performed during Operational Qualification (OQ) testing?
Guidelines stress the importance of equipment qualification simulating actual production conditions, including 'worst case' situations and that "tests and challenges should be repeated a sufficient number of times to assure reliable and meaningful results." "three consecutive batches" is recommended for process validation rather than for equipment qualification. No specific number of "runs" for equipment qualification, but multiple tests to simulate actual operating ranges and to establish consistency are expected
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Qualification of Equipment
IF ONE TYPE AND MODEL OF EQUIPMENT IS QUALIFIED, CAN IT BE USED IN A DIFFERENT PROCESS WITHOUT ADDITIONAL QUALIFICATION? For IQ document whether each equipment is installed correctly and operates consistently according to established limits and tolerances. OQ should also be performed for each different use of the equipment or system to document the suitability for that use Not be required for additional pieces of the same type/model of equipment when used in the same process or for each piece of the same type/model of equipment used in the same process, provided installation qualification has been performed
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Validation
Performance qualification
Verifies that the equipment performs according to design specifications and user defined requirements in a reliable and reproducible manner under normal production conditions.
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Qualification Plan
To ensure that requirements are met and confirm by examination and collection of objective evidence
- Challenges to equipment to be designed
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Qualification Plan
1. Purpose 2. Scope 3. Equipment Description 4. Operational Specifications 5. Acceptance Criteria
6. Testing Results
7. Discrepancies/Corrective Actions
8. Conclusions/Final Report
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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
Validation
The next slide shows a typical format for:
7.2
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Qualification Plan
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Conditions that include upper and lower processing limits Circumstances that present the highest chance of process or product failure relative to ideal situations Identify those conditions that are likely to be experienced during routine manufacture/process
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More Examples
The following case illustrates the importance of performing adequate equipment qualification on each piece of processing equipment A pharmaceutical firm used two blenders to produce a tablet. Both blenders from same equipment manufacturer, same model number and same design. Supplier told the drug manufacturer that the units were "identical." though one was older. Manufacturer did not include the older blender as part of its process validation. Company marketed about 100 batches of tablets using the old blender. Retention samples showed some batches failed content uniformity investigation showed out of specification batches were from one of the two "identical" blenders the old one. The older blender had a slightly smaller capacity and different operational characteristics (RPMs) when run at the same settings as the newer blender. Subsequently, the firm recalled its total production of the product it made using the older blender. The firm decided to qualify the old blender using production size lots.
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Validation
Qualification of in-use systems and equipment
Data to support and verify the suitable operation and performance of systems and equipment Should include operating parameters and limits for critical variables, calibration, maintenance and preventive maintenance, standard operating procedures (SOPs) and records
9.1 9.2
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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If any question is answered Yes, the operation/function should be considered as GMP relevant. During risk assessment, the probability of occurrence and detectability should be considered and measures to reduce the risk identified.
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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda
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Requalification
Required for: - significant change in batch size - change in operating parameters - component specifications have changed - new accessories or components are added to previously qualified equipment - process changes that potentially impact product effectiveness or quality
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Some Experiences
What if the results are not good? Study report destroyed and manufacturer pretends it never happened
Annex 6
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