Here you will find answers to the following questions:
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The validation of processes and the qualification of buildings and apparatus as a prerequisite for the process validation requires a considerable investment in terms of personnel, time and money. The tasks at issue should not be carried out as a side job and require full support from the management board. It is therefore important to determine in writing the general strategy and philosophy of a company on the topic of validation from the point of view of the management board, e.g. in the form of a validation policy or validation philosophy. This rather general declaration of intent demonstrates the general attitude of a company regarding validation problems internally (management board, staff) and externally (customers, authorities).
The validation policy can be an independent document, part of a quality assurance manual or a validation master plan.
Beyond the general declaration of intent, the validation master plan documents the structured approach of a company to validation projects (see chapter 2 Example of a validation master plan). The official rules contain the definitions cited in figure 1.
Definition of a validation master plan |
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In accordance with PIC/S PI 006 (4.3.1): In accordance with Annex 15, EU GMP Guideline (2): |
Function of the validation master plan |
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Pharamceutical companies tend to complain that there are no binding guidelines from the legislator for the procedure of how and when validations are to be carried out, and even terminology and contents vary. Quite the contrary, this should be considered as invaluable scientific and corporate freedom. After all, the most varied solution possibilities are conceivable - and each pharmaceutical company is permitted to define an individual validation strategy optimized to its own organisation and product range: the validation master plan is the correct place for defining and justifying a company's individual understanding of validation, as well as company-specific definitions and contents.
A VMP should also point out that validation is not understood as an isolated task, but rather as a continuous process, and should explain that (and how) the required GMP- environment is provided ( e.g. maintenance,, documentation, training, change control).
The type and content of the validation master plan can vary greatly (see chapter 3 Example for a validation matrix). A validation master plan can, for example, give a general overview of the qualification and validation work for a manufacturing site planned from scratch. In this case it is a useful planning tool for the project management, and scope and contents will differ significantly from other VMPґs, e.g. a validation master plan for a manufacturing facility in old buildings, producing a great variety of drug products already marketed for years, but which have never undergone a formally documented validation process. This type of validation master plan is primarily used to define rationales for bracketing, to set priorities and to evaluate the risk for products, where validation has not yet been performed.
If there is extensive validation work to be done for one product, it can be advantageous to write an individual validation master plan for this product in order to "unburden" the individual validation protocols..
In contrast, a validation master plan for a global corporate group has a completely different focus: the concepts and strategies valid for all country representations should be specified here - without being able to go into the local task assignments and responsibilities in much detail
Various types of validation master plan (VMP) |
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VMP as a part of project management |
e.g. for the setting up and qualification of new manufacturing sites |
Cross-project VMP |
e.g. for a manufacturing facility with old preparations: for recording and grouping products |
VMP as a global validation concept of a global corporate group |
Determination of corporate strategies, terminology, acceptance criteria; additional, local master plans may be necessary |
Product-related VMP |
in case of extensive validation work for a product |
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Basic elements that each validation master plan should contain are specified in PIC/S PI 006 and appendix 15 to the EU GMP Guideline (see also figure 4).
The validation master plan should be clear and concise and not repeat the contents of other documents unnecessarily. Cross-references to existing documents are useful here instead. A validation master plan should be confirmed and approved by the management.
Elements of the validation master plan (in accordance with PIC/S PI 006) |
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The VMP as a summarising document provides external parties (clients, customers or the authorities) with the possibility of quickly gaining an overview of the validation strategies of a company. This aspect is particularly interesting for contract manufacturers because the validation often represents a part of the service provided.
1 Validation matrix
A validation matrix, as a component of the validation master plan, is a table which lists all products, processes or systems that have to be qualified or validated and allocates the required action to be taken:
- Scale of the qualification (DQ, IQ, OQ, PQ)
- Cleaning validation
- Method of process validation (prospective, concurrent, retrospective)
- Revalidation activities
- Current status, future planning
- Group/family formation; bracketing and matrixing
The individual activities in the matrix should be indicated with priorities and responsibilities and enable an overview of complex validation projects (PIC/S PI 006).
Formation of product families or product groups; bracketing and matrixing
In particular, when a large number of drug products are to be validated, already marketed for years, it is often necessary for reasons of time and cost to summarise the different strengths of a product or similar products during the process validation, in order to reduce the validation effort. In this case, there are various strategies:
Matrixing: By this approach, the manufacturing processes for various strengths of the same drug product are validated together. The formulations and manufacturing processes must be the same. If there are differences in the composition or manufacturing processes, a risk analysis must be carried out to evaluate the effects that this could have on the validation result. Fewer than three validation batches can be manufactured for each strength if this is scientifically justified in the validation master plan or in the validation protocol. It is not advisable, however, to produce no validation batches at all from individual (e.g. the middle) dosages, because the FDA wants to see the validation of a - no exact figures - "minimum number of production batches for each strength".
Family grouping: This concept is intended to create a combined validation protocol for validating the procedure for different but related drug products.
In this case, it is of particular importance to thoroughly justify why the drug products grouped together into a product group may be validated together. All variations in the formulation or method of manufacture must be described and evaluated in detail (risk analysis). If, however, there are major variations in the equipment used or the procedures performed, each drug product has to be validated separately.
Bracketing: The bracketing concept considers only extreme cases, e.g. the worst case scenario. This may include, for example, preparations with the highest and lowest dosage, drug substances with the best and worst water solubility, the lowest and highest mixing load, the best and worst flow capabilities, etc.
To use the bracketing concept for the process validation, note that a well-justified written reasoning must be submitted to explain why the opinion is that the intermediate strengths, preparations, loads or other features can be extrapolated from the results for the extreme cases. Despite this, a minimum number of production batches must be included in the validation for each drug product and each dosage. This minimum number, however, has not yet been defined and can be determined and justified individually.
For all three procedures, the pharmaceutical company is obliged to develop and justify a procedure suitable for the particular case and to consider similarities/differences between the various strengths or different drug products.
2 Example of a validation master plan
Pharmaceutical |
Validation master plan |
P. x of y |
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VMP-0815-4711 |
Validation master plan for Ixberg site |
valid from 01.05.2003 |
1. Scope This validation master plan applies at the Ixberg site for the process validation of solid dosage forms. It also refers to products manufactured at a contract for other pharmaceutical companies. Furthermore, it is the basis for the process validation of products manufactured and validated by contract manufacturers for the Pharmaceutical company company. This document is binding for all staff in the GMP area involved directly or indirectly in the manufacturing of solid dosage forms as well as external consultants on the payroll. This validation master plan does not apply for bio-technological products manufactured from 2004 in the new facility B6780. The procedure for these products is regulated in a separate validation master plan. This validation master plan does not include the cleaning validation and computer validation. The procedures for the cleaning validation and computer validation are defined in separate validation master plans. 2. Key terms Validation master plan, process validation, validation manager, validation team, validation matrix, statistical techniques, revalidation, qualification, prospective validation, retrospective validation, concurrent validation, change control, deviations, raw material quality, product groups, matrixing, bracketing, contract manufacturers, critical processing steps, testing schedule, acceptance criteria, risk analysis, failure cause analysis, product file, annual product review, APR |
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3. Content 1. Scope page 6 2. Key terms page 6 3. Content page 7 4. Validation policy page 8 5. Organisation and responsibilities page 8 6. Company-specific definitions page 10 7. Format of documents and archiving page 10 8. Description of project page 11 9. Family grouping, bracketing and matrixing page 11 10. Quality of the raw materials used page 12 11. Qualification status of the facilities and equipment used, 12. Validation of analytical methods page 12 13. Risk analysis page 12 14. Critical processing steps and process parameters page 12 15. Determination of the test plan page 13 16. Determination of the acceptance criteria page 13 17. Sampling plan page 14 18. Reference documents page 14 19. Schedule page 15 20. Techniques for test interpretation page 15 21. Changes to the validation protocol page 15 22. Control of changes to validated processes or systems page 16 23. Distribution list page 16 24. Change history page 16 Appendices: Appendix 1: Validation matrix including schedule and capacity estimate Appendix 2: Test plan Appendix 3: Distribution list |
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4. Validation policy It is an aim of Pharmaceutical company to exclusively manufacture products for trade whose manufacturing procedure is reproducible, so that defective batches, overhauls and waste can be avoided and the health of patients is never put into jeopardy. An important tool for achieving this aim is the process validation, which is a basic element of the Pharmaceutical company quality assurance system. The validation process involves all measures and their documentation which prove that procedures and processes yield reproducible products that correspond to the previously defined specifications. A prerequisite is that the building, facilities, equipment, machines, computers, staff and suppliers of raw material involved are suitable (qualified) for the intended use. With our concept of process validation, we want to comply with legal requirements and meet the expectations of our customers with the obligations resulting from our ISO 9001-2000 certification. 5. Organisation and responsibilities The head of production is responsible for process validation at Pharmaceutical company. He provides the necessary capacities and guarantees the time frame in production planning required for the validation. The head of production approves the master production record to be validated. He delegates coordination and execution of validation projects to the validation manager responsible. The validation manager appoints project-specific validation teams, made up of representatives from the relevant departements (pharmaceutical production, quality control, engineering, regulatory affairs department, etc.) and a member from QA. These teams can also be assisted by external consultants if necessary. Decisions are made by the team and approved by the validation manager after consulting the head of production. If necessary, each validation project can be divided into further validation projects. Each individual project can be managed and processed by the corresponding specialised departments. All staff involved in the planning and execution of the process validation must be able to demonstrate profound knowledge in the area of validation - additional to the regular GMP training (SOP 700-120-03 GMP training plan) - and with regards to validation master plans and validation protocols at Pharmaceutical company. The validation team is responsible for identifying training shortfalls and the training coordinator is responsible for organising the training. To guarantee that the resources necessary for planning and executing the validation projects are provided, the validation master plan is finally authorised by the general management. |
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Tasks of the validation team:
Tasks of the validation coordinator:
Tasks of the head of production in this context:
Tasks of the Qualified Person in this context:
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6. Company-specific definitions Process validation is establishing documented evidence that production or packaging procedures are highly likely to consistently produce a product compliant with the specifications. The term "process validation" is not used at Pharmaceutical company for the cleaning validation or validation of analytical methods or for qualification steps. The validation process involves all measures and their documentation which prove that procedures and processes yield reproducible products that correspond to the previously defined specifications. Qualification is documented evidence of the suitability of buildings, facilities, equipment, machines, computers, staff and suppliers of raw materials for the intended use. Successful qualification is a prerequisite for the execution of process or method validations. The qualification of buildings, facilities, equipment, machines and computers is a process of several consecutive steps; the individual steps are described in the qualification master plan QMP 9907834. Prospective validation is applied for all new processes or newly-developed products. The general procedure for prospective validation is regulated in the SOP 100-200-01 Prospective validation of a new manufacturing procedure. Retrospective validation is restricted to those drug products already marketed for long time, which have never undergone formal documented validation up to now. The prerequisites to be met and criteria to be fulfilled so that a process validation can be executed retrospectively are regulated in the SOP 100-210-01 Retrospective validation of manufacturing procedures for old drug products. Concurrent validation is only possible in few cases that are to be well justified in writing. The details are regulated in the SOP 100-230-01 Concurrent validation of manufacturing procedures for transfer to other sites or in the case of slight changes to the procedures. „Critical" factors, processing steps or parameters are those, where a slight change to this parameter or its environment has a significant influence on the process reliability or the quality of the final product. Critical factors are identified with the aid of risk analysis. For further definitions, see the SOP 200-100-03 Definitions and terms. 7. Format of documents and archiving All documents created as part of the validation procedure must correspond with the specifications in the SOP 100-505-02 Creation of validation documents and the respective current templates in the Intranet under Pharmafirma\QA\database\templates\Validation. This also applies for validation documents created by external companies. However, in some cases, it is possible to copy test plans and test reports from external companies into the validation documentation. A prerequisite is that these documents have cover sheets in the format used by Pharmaceutical company. This is the only way to guarantee unique identification and archivability in the Pharmaceutical company archiving system in accordance with the SOP 100-510-04 Archiving GMP-relevant documents. |
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8. Description of project Each validation protocol must include a precise description of the product and the process to be validated in the form of a flow chart. A number must be assigned to each processing step (see SOP 100-505-02 Creation of validation documents) so that this step can be referenced unambiguously. This VMP applies for the following four product groups:
All process validation projects to be carried out within the scope of this VMP, including schedules, priorities and capacity estimations are listed in appendix 1 (see chapter 3 Example for a validation matrix). 9. Family grouping, bracketing and matrixing In order to reduce validation workload, it is possible to define product groups, equipment groups or groups with similar production processes. However, there must be a written, scientific rationale in any case. This approach allows to define and validate the "worst case" within each group, e.g. the most demanding product, the most complicated equipment, the most complex manufacturing procedure, the most unfavourable batch size). It is also possible to address various dosages of a drug product in the same validation protocol according to a bracketing or matrixing concept, as long as the formulation and manufacturing procedure are comparable. Prerequisites for the application of bracketing/matrixing or family grouping:
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10. Quality of the raw materials used The specifications of the raw materials to be used and the suppliers approved for each raw material are documented in the respective validation protocol. For common raw materials, the specifications and suppliers usually used at Pharmaceutical company should be preferred. If it is necessary in some cases to define exceptional specifications or suppliers for a particular validation project, this must be justified in the validation protocol. The suppliers listed in the validation protocol must be qualified. 11. Qualification status of the facilities and equipment used, including measuring instruments The validation protocol must list in detail all machines, facilities, measuring instruments and recording instruments used. The exact equipment type and, if necessary, size must be fixed because the result of the process validation is always only valid for the facilities and machines used in the validation runs. Transferability to similar or other equipment must be proven, where necessary, with revalidation. The qualification status of each of these pieces of equipment must be documented in the validation protocol. The calibration status of the measuring instruments should also be noted. If alternative equipment is permitted for certain processing steps, e.g. different types of blenders, this must be explained in the validation protocol. The validation must be planned in such a way that suitable data material is collected for all specified types of blenders. In this case even more than three validation batches may be required. 12. Validation of analytical methods Valid analytical methods must be prepared for the testing defined in the validation protocol. The validation status of the analytical methods is documented in the validation protocol. 13. Risk analysis (At least) one risk analysis is carried out before or during the creation of a validation protocol. As part of this risk analysis, possible deviations/failures are identified for each processing step and the significance of the effect of these deviations on the quality of the final product is assessed. The processing steps and critical process parameters identified in this way must be validated. For more details see SOP 100-640-01 Carrying out risk analyses. The results of the risk analysis are documented as described in the SOP and are part of the validation protocol as an appendix. 14. Critical processing steps and process parameters As a result of risk analysis, the processing steps are divided into noncritical and critical. Critical processing steps require validation. A test plan, including testing criteria, a sampling plan and acceptance criteria must be created for each critical processing step. |
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15. Compliation of test plans A test plan for each critical processing step is appended to the validation protocol, with detailed descriptions of the tests to be carried out as part of the validation (see chapter 4 Example for a test plan). These are basically investigations that are carried out for validation purposes in addition to the normal in-process controls specified in the manufacturing instructions. Tests may include:
The test plan must also establish:
16. Determination of the acceptance criteria The validation protocol and test plan list the expected results and acceptable ranges of variations. If the validation runs do not comply to these acceptance criteria, this may be a hint to the fact, that the process in not under control. Acceptance criteria must always be defined in advance, prior to the start of the first validation run. The appropriate selection of acceptance criteria is crucial for the outcome of the validation project and is therefore a core element of the validation protocol. When drawing up acceptance criteria, the following must be taken into consideration:
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17. Sampling plan When planning the process validation, particular attention must be paid to the generation of detailed sampling plans and to correct sampling because unsuitable sampling rarely leads to a meaningful test result. For critical manufacturing levels in particular, it is of vital importance that there are precise explanations for whether, for example, samples are taken regularly during a manufacturing operation or from different places in the container. Required details in the sampling plan (cf. SOP 300-240-02 Sampling instructions and plans):
The intended use must be noted for all samples. Samples must not be taken "just in case". In contrast, the test plan can allow for specific testing (e.g. content uniformity), e.g. 40 samples to be taken according to the plan, only 20 of which are to be tested initially and the other samples only to be analysed in a predetermined case (e.g. standard deviation exceeds xyz). 18. Reference documents For a better understanding and clarity, each validation protocol and report must list the relevant reference documents, for example, standard operating procedures, development reports, reports about pilot batches, IQ/OQ/PQ reports, etc. The following documents are valid together with this validation master plan: 1. the qualification master plan QMP 9907834 2. the following SOPs (the current versions):
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19. Schedule Manufacturing validation batches takes considerably more time than routine production. It is important to take this aspect into consideration when scheduling production and to draw up a detailed schedule to prevent misunderstandings and bottlenecks. The three validation batches must be scheduled for manufacture on different days, with different staff or during different shifts, if possible, to make this as realistic as possible. The schedule and capacity estimate for this VMP are found in appendix 1 (see chapter 3 Example for a validation matrix). 20. Techniques for interpretation of test results In order to prevent validation results from being subsequently influenced by choice of questionable statistical techniques, the validation protocol and test plan must establish the methods and statistical testing to be used for the interpretation of the test results (cf. SOP 900-330-02 Statistical techniques for test evaluation). The use of outlier tests is generally not permitted (exception: biological and microbiological tests in accordance with SOP 007-014-02). Significantly different test results are subject to the OOS procedure in accordance with the SOP 400-500-02 Handling of OOS (out-of-specification)-results. However, if this concerns deviations from the targets as part of the process validation rather than deviations from specifications, a written failure cause analysis is performed instead. 21. Changes to the validation protocol If changes to originally planned procedures are necessary during the process validation, the validation protocol must be modified. Either the relevant test plan can be revised (new version number, reason for change), or a new version of the validation protocol can be composed, e.g. in the case of considerable changes. Each change must be approved before being implemented. All staff involved in the validation work must be informed about the changes. Planned changes to the formulation, process, facilities, buildings and analytical methods are also subject to the change control procedure in accordance with the SOP 400-600-03 Reporting, evaluating and carrying out planned changes (Change control). |
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22. Control of changes to validated processes or systems As soon as a process or system is validated, i.e. the corresponding validation documentation has been approved by quality assurance, changes can be made to the process or system but only in accordance with the SOP 400-600-03 Reporting, evaluating and carrying out planned changes (Change control). A product file is saved containing the following current results (with reference to original documents) for each product where process validation is complete:
This product file is evaluated yearly (at the latest during the month of the validation approval) in accordance with the SOP 100-500-02 Annual Product Review, APR to check whether the process can still be considered validated. 23. Distribution list See appendix 3 for the current distribution list for this VMP. 24. Change history
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3 Example for a validation matrix
Pharmaceutical company |
Validation matrix |
P. x of xx |
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VMP-0815-4713 |
Appendix 1 to Validation master plan VMP-0815-4711 for Ixberg site |
valid from 01.05.2003 |
All process validation projects to be carried out as part of VMP-0815-4711 are listed with time and capacity estimates and priorities in tables in this appendix (validation matrix). Matrixing, bracketing and prioritisation are based on individual risk analyses (RA-0815-9912 to RA-0815-9922). |
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Name |
Product no. |
Qualification |
Process |
product group |
Time frame |
Capacity |
---|---|---|---|---|---|---|
Powder and effervescent granules |
31XXX |
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bPowder |
315258 |
yes |
12 |
Dec. 03 - Jan. 04 |
20 |
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cPowder |
315269 |
yes |
13 |
Dec. 03 - Jan. 04 |
30 |
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dGranulates |
315300 |
yes |
4 |
Group A |
Aug. - |
40 |
dGranulate forte |
315325 |
yes |
4 |
Group A |
Aug. - |
see above |
tablets - directly compressed |
95XXX |
|||||
r tablets |
957834 |
yes |
7 |
Oct. - |
25 |
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s tablets |
957869 |
yes |
3 |
Group B |
May - |
50 |
s-Retard tablets |
957641 |
no |
8 |
Oct. - |
15 |
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t- tablets |
957693 |
yes |
3 |
Group B |
see above |
see above |
t- tablets forte |
957695 |
yes |
3 |
Group B |
see above |
see above |
u- tablets |
959695 |
yes |
9 |
Oct. - |
30 |
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tablets |
94XXX |
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v tablets |
947834 |
yes |
10 |
Nov. - |
15 |
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vRetard tablets |
947847 |
yes |
11 |
Nov. - |
10 |
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w tablets |
947941 |
yes |
5 |
Group C |
Sep. - |
30 |
w tablets forte |
947943 |
yes |
5 |
Group C |
see above |
see above |
Film coated tablets |
97XXX |
|||||
xTabs |
978634 |
yes |
12 |
Jan. - |
25 |
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yRetard tablets |
978347 |
yes |
13 |
Jan. - |
50 |
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zLong tablets |
978941 |
yes |
14 |
Jan. - Feb. 04 |
30 |
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Sugar coated tablets |
99XXX |
|||||
mSugar coated |
998783 |
yes |
15 |
Feb. - |
20 |
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nSugar coated tablets |
997834 |
yes |
16 |
Feb. - |
25 |
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Capsules |
56XXX |
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eCapsules |
569834 |
yes |
17 |
Apr. - |
40 |
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fCaps long |
569878 |
yes |
18 |
Apr. - |
20 |
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gCapsules |
569883 |
yes |
6 |
Group D |
Sep. - |
30 |
gCapsules forte |
569884 |
yes |
6 |
Group D |
see above |
see above |
Pellets |
66XXX |
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oPellets |
667841 |
yes |
1 |
Group E |
May - |
40 |
pPellets |
667834 |
yes |
1 |
Group E |
see above |
see above |
pPellets retard |
667342 |
yes |
1 |
Group E |
see above |
see above |
qPellets forte |
667830 |
yes |
1 |
Group E |
see above |
see above |
qPellets retard |
669878 |
yes |
2 |
June - |
20 |
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qPellets long |
669734 |
no |
2 |
June - |
30 |
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Primary packaging: blister |
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957834 |
yes |
19 |
Group F |
May 04 |
15 |
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957869 |
yes |
19 |
Group F |
May 04 |
see above |
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957641 |
no |
20 |
Group G |
June 04 |
20 |
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957693 |
no |
20 |
Group G |
June 04 |
see above |
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957834 |
no |
20 |
Group G |
June 04 |
see above |
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957869 |
no |
20 |
Group G |
June 04 |
see above |
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957641 |
no |
20 |
Group G |
June 04 |
see above |
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957693 |
no |
21 |
Group H |
July 04 |
15 |
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957695 |
no |
21 |
Group H |
July 04 |
see above |
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959695 |
no |
21 |
Group H |
July 04 |
see above |
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947834 |
yes |
19 |
Group F |
May 04 |
see above |
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947847 |
yes |
19 |
Group F |
May 04 |
see above |
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947941 |
yes |
22 |
Group I |
Sep. 04 |
25 |
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947943 |
yes |
22 |
Group I |
Sep. 04 |
see above |
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978634 |
yes |
22 |
Group I |
Sep. 04 |
see above |
|
978347 |
yes |
22 |
Group I |
Sep. 04 |
see above |
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978941 |
yes |
22 |
Group I |
Sep. 04 |
see above |
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998783 |
yes |
23 |
Group K |
Oct. 04 |
15 |
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997834 |
yes |
23 |
Group K |
Oct. 04 |
see above |
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569834 |
yes |
22 |
Group I |
Sep. 04 |
see above |
|
569878 |
yes |
22 |
Group I |
Sep. 04 |
see above |
|
569883 |
yes |
23 |
Group K |
Oct. 04 |
see above |
|
569884 |
yes |
23 |
Group K |
Oct. 04 |
see above |
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Filling of sachets |
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315258 |
yes |
24 |
Group L |
Sep. 04 |
20 |
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315269 |
yes |
24 |
Group L |
Sep. 04 |
see above |
|
315300 |
yes |
24 |
Group L |
Sep. 04 |
see above |
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315325 |
yes |
24 |
Group L |
Sep. 04 |
see above |
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669734 |
no |
25 |
Oct. 04 |
10 |
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Final packaging |
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957834 |
yes |
26 |
Group M |
May - June 04 |
30 |
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957869 |
yes |
26 |
Group M |
May - June 04 |
see above |
|
957641 |
no |
27 |
July 04 |
10 |
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957693 |
yes |
26 |
Group M |
May - June 04 |
see above |
|
957834 |
yes |
26 |
Group M |
May - June 04 |
see above |
|
957869 |
yes |
28 |
Group O |
July 04 |
15 |
|
957641 |
yes |
28 |
Group O |
July 04 |
see above |
|
957693 |
yes |
28 |
Group O |
July 04 |
see above |
|
957695 |
yes |
26 |
Group M |
May - June 04 |
see above |
|
959695 |
yes |
26 |
Group M |
May - June 04 |
see above |
|
947834 |
no |
29 |
Sep. 04 |
10 |
||
947847 |
yes |
30 |
Sep. 04 |
15 |
||
947941 |
yes |
26 |
Group M |
May - June 04 |
see above |
|
947943 |
yes |
26 |
Group M |
May - June 04 |
see above |
|
978634 |
yes |
26 |
Group M |
May - June 04 |
see above |
|
978347 |
yes |
26 |
Group M |
May - June 04 |
see above |
|
978941 |
yes |
28 |
Group O |
July 04 |
see above |
|
998783 |
yes |
28 |
Group O |
July 04 |
see above |
|
997834 |
no |
31 |
Sep. 04 |
15 |
||
569834 |
yes |
32 |
Group P |
Oct. - |
20 |
|
569878 |
yes |
32 |
Group P |
Oct. - |
see above |
|
569883 |
yes |
32 |
Group P |
Oct. - |
see above |
|
569884 |
yes |
32 |
Group P |
Oct. - |
see above |
|
315258 |
yes |
32 |
Group P |
Oct. - |
see above |
|
315269 |
no |
33 |
Dec. 04 |
15 |
||
315300 |
no |
34 |
Dec. 04 |
10 |
||
315325 |
yes |
32 |
Group P |
Oct. - |
see above |
|
669734 |
yes |
32 |
Group P |
Oct. - |
see above |
|
Total |
875 |
4 Example for a test plan
Pharmaceutical company |
Test plan for |
P. x of xx |
---|---|---|
VMP-0815-4715 |
Enclosure 2 for the validation master plan for solid dosage forms for the Ixberg site |
valid from 01.05.2003 |
Validation project: example - tablets 0.5 mg Sampling: 1. For blending uniformity: 2. For angle of repose |
||
|
|
|
|
|
|
|
|
Pharmaceutical |
Test plan for |
P. x of xx |
VMP-0815-4715 |
Enclosure 2 for the validation master plan for solid dosage forms for the Ixberg site |
valid from 01.05.2003 |
Batch |
#03 06 135 |
# 03 06 136 |
#03 06 137 |
|
---|---|---|---|---|
Batch size |
500,000 pc |
650,000 pc |
500,000 pc |
|
Equipment/machine |
Fantasy blender I |
Fantasy blender I |
Fantasy |
|
Machine parameters |
||||
|
200 UpM |
250 UpM |
150 UpM |
|
|
10, 15, 20 mins |
10, 15, 20 mins |
10, 15, 20, 25 min |
|
Test parameters |
||||
|
yes |
yes |
yes |
|
|
yes |
yes |
yes |
|
Sample number |
||||
|
3 * 9 samples: |
3 * 9 samples |
4 * 9 samples |
|
|
3 * 3 samples |
3 * 3 samples |
4 * 3 samples |
Acceptance criterion |
Content Uniformity |
Angle of repose alpha |
||
---|---|---|---|---|
Mean value |
x = 98 - 102 % labelclaim |
< 30° |
||
Single values |
no value < 95 % or > 105 % |
no value > 40° |
||
Standard deviation |
srel < 1.5 % |
srel < 2.5 % |
Summary The validation master plan (VMP) is a document required in the PIC/S guideline PI 006 and in appendix 15 of the EU GMP Guideline, which serves to structure and control the validation work. The general procedure for validation projects, responsibilities and company-specific terminology is defined in the validation master plan. The VMP can be structured in different ways according to the application area. A VMP can, for example, cover the corporate validation strategy of a global group, or concern only a single drug product. The VMP is used for internal and external communication. |