1.0 Purpose
1.1 To provide documents evidence and procedure of process validation which confirm that a process is capable of reliably and repeatedly rendering a product of the required quality.
2.0
Scope
2.1 This SOP is applicable for process
validation of all products of "NAME" Pharmaceuticals Ltd.
3.0 Responsibility
3.1. Product Development department will form a validation team with the help of Production, QA, QC and Engineering department.
3.2. Product Development department shall be responsible to prepare the process validation protocol for the batches to be validated, co-ordinate the entire process validation activity related to the protocol, preparation of report & summary.
3.3. Engineering department shall be responsible to provide the utilities, status of calibration & preventive maintenance.
3.4. Quality Assurance department shall be responsible to review & appropriate the process validation protocol, co-ordinate the entire process validation activity related to the protocol.
3.5. IPQA shall be responsible to arrange the sample for analysis as per protocol.
3.6. Quality Control department shall be responsible for analysis of the finished product as per protocol.
4.0 Abbreviations and Definitions
4.1 SOP= Standard Operating Procedure
4.2 QA= Quality Assurance
4.3 PD= Product Development
4.4 QC= Quality Control
4.5 STP= Standard Testing Procedure
4.6 IPQA= In-Process Quality Assurance
4.7 PIC/S= Pharmaceuticals Inspection Co-operation Scheme
4.8 Process Validation: process Validation is the process of ensuring and providing documentary evidence that process (within their specified design parameters) is capable of repeatedly and reliably producing a finished product of the required quality.
5.0 Materials and Equipment
5.1 Not Appreciable
6.0 Precaution / Health and Safety Considerations
6.1 Approved validation protocol before starting the process validation activity.
6.2 Identify critical steps before process validation activity.
6.3 Follow validation protocol strictly during process validation activity.
6.4 Collect data and review against predetermined acceptance criteria, while should be reflected in process validation reports.
7.0 Procedure
7.1 Validation Procedure
7.1.1 Product Development department will prepare a validation protocol for three consecutive batches to validate the whole process and get approval from QA.
7.1.2 Product Development department will arrange the necessary materials, manpower, equipment and are to execute the batch manufacturing record and batch packaging record as per protocol.
7.1.3 Product Development department will follow up critical process parameter as per protocol in every stage of process validation activity.
7.1.4 IPQA department will arrange the sample for analysis as per protocol.
7.1.5 Product Development department will analyze bulk and intermediate product as per protocol.
7.1.6 Quality Control department will analyze the finished product as per approved STP.
7.1.7 Quality Assurance will collect and review all analytical reports to release the product.
7.1.8 Product Development department will prepare the validation report on the basis of batch document and process validation report.
7.2 Validation Protocol
A validation protocol should be prepared before starting the process and the following steps/parameter should be included in the protocol (Annexure-I) as draft/sample.
- Process description, Master Formula & Flow Chart
- Details of the equipment/facilities with its calibration status
- Personnel responsibilities
- Sampling plan
- Product Specification & Acceptance limit.
- Critically assessment for process stages, control variables & measuring response justification
7.3 Critical Process and Testing Parameters
The purpose of the critical process parameter is to identify, evaluate and document the critical process parameters, which have a significant effect on the process or the quality of the product and to describe the ranges of the operational parameters that lead to a compliant product (design space), based on actual data generated at lab, pilot and full scale. The process must be validated within a specified range of operational for the identified critical process parameters.
Table
1: Example of potentially critical parameters for oral solid dosage form
|
Example of potentially
critical parameters |
Example of quality characteristics to be monitored |
|
-
Drug substances
specification |
- Disintegration
time |
|
-
Excipients specification |
- Dissolution
rate |
|
-
Mixing & choppering
speeds times |
- Content
uniformity |
|
-
Quantity of granulation
liquid |
- Weight
uniformity |
|
-
Sequences and speed of
adding components |
- Friability |
|
-
Compression/ ejection force
during tabletting |
- Hardness |
|
-
Spray rate, inlet/out air
temperature of the coater |
- Thickness |
|
-
Drum rotation speed |
- Homogeneity
(blend uniformity) |
|
-
Process time |
- Yield |
|
-
Amount of used film coating
suspension/solution |
- Loss
on drying/ Moisture content |
Table
2: Example of potentially critical parameters for oral solid dosage form
|
Example of potentially
critical parameters |
Example of quality characteristics
to be monitored |
|
-
Drug substances
specification |
- Homogeneity
|
|
-
Excipients specification |
- Yield |
|
-
Packaging material
specification |
- pH |
|
-
Temperature of solvent |
- Filling
volume weight & sealing |
|
-
Sequences and speed of
adding components |
- Microbial
status |
|
-
Dissolving time |
- Viscosity |
|
-
Stirrer speed time stirring |
- Particle
size dispersed drug |
|
-
Drum rotation speed |
- Biological
activity |
|
-
Process time |
- Stability
immediate |
|
-
Amount of used film coating
suspension/solution |
|
If required, one or more optimization batches (smaller than the standard batch size) can be produced using the production facilities for detailed assessment of process parameters. Protocol and Report for optimization batches have to be maintained.
7.5 Re-validation
Revalidation is required based on the assessment in the change request whenever there are changes in the process, components, equipment/ facilities or the stating materials, which could impact on product effectiveness or product characteristics and whenever.
Revalidation for non-sterile products has to be performed after two years only for highly regulated market and five years for others market depending on trend, modifications, deviations and/or changes assessed in the annual product review/ product quality review.
The documentation for revalidation is to be established in the same way as for the initial validation.
A formal change control to initiate which defines how changes are evaluated and managed.
In case of planned changes, it has to be considered whether and to what extent a revalidation of the process has to be performed. In case of deviations, resulting in e.g. failing analytical results, the process has to be thoroughly investigated and the root cause determined. The affected process steps have to be reviewed and optimizes process may have to be validated, based on a risk assessment.
Examples of changes:
Manufacturing:
changes of the manufacturing procedure, specifications, analytical procedures
-
Drug substances: Changes of
the route of synthesis, of physical properties, of specifications, of supplies
-
Excipients: Changes of
supplier, change of specifications
-
Equipments: Changes of type or
size, change in maintenance and/or calibration, change of cleaning procedure
-
Batch size
-
Change in the facility and/ or
plant (location or site)
-
Production area support system
-
Accumulation of a number of
minor changes
7.6 Validation report
The process validation report documents the validation activities performed. It presents all pertinent findings and conclusion, especially the validation status. It has to contain at least the following as draft/sample.
- The study objective and a reference to be validation protocol.
- A summary of the performed activities with conclusions and validation status.
- Any deviations from the protocol, from the process or the acceptance criteria set with short description, evaluation, assessment, corrective/ preventive action as needed and conclusion. A documented investigation of any deviations from the protocol, from the process or the acceptance criteria set and of any analytical OOS result must be performed, including the discussion of the effects on the process and product quality and the conclusions to be drawn. Deviations in the analytical laboratory (out-of-specification {OOS} test results assigned to laboratory error) must be subjected to investigations according to applicable SPs. Any aborted validation attempts or rejected batches must be includes in the discussion.
- The starting materials used including batch numbers or a reference to attached batch
- documentation.
- Facilities, equipment and control instruments used or a reference to the validation protocol or
- A detailed summary of all results, as required by the validation protocol from in process controls,
- final testing and additional testing. The results have to be compared with their acceptance criteria as defined or referenced in the validation protocol.
- Results of any supplementary studies as defined in the validation protocol.
- The decision to accept or not accept the validation study and as appropriate the rationale.
- Anny corrective or follow-up actions needed.
- As appropriate recommendations with respect to the extent and frequency of monitoring and in-process controls and their limits necessary routine production based on the experience from the validation batches.
- Final process parameters and their corresponding ranges
- Actions to be taken in the event of the acceptance limit being exceeded
- Short assessment/ reference to transport studies and stability reports for bulk holding times and final product as appropriate.
- The conclusion and recommendation should be incorporated in to the batch manufacturing and the batch packaging documents. Action to be taken in the events of limits being exceeded should be specified.
7.7 Release Procedure of Validation Batches
After completion of validation of one batch a preliminary release notification documents will be approved by QA intended to be sold or supplied when all raw data has been generated, reviewed and meets the pre-determined acceptance criteria and when all deviations or OOS results have been investigated, evaluated, assessed, resolved documented and approved by QA.
On the basis commercial distribution of the drug product will be initiated while the validation report is being completed.
8.0 Reference Document
8.1 As per WHO GMP guideline, Volume 2
8.2 PIC/s; PI 006-3, 25 September 2007
9.0 Annexure
9.1 Not Appreciable
10.0 Revision History
|
Revision No. |
Brief
reason for the revision |
Effective Date |
Remarks |
|
01 |
New |
|
|
|
02 |
|
|
|
11.0 Training
11.1 Head of Product Development or his/her nominee shall give the SOP training before effective date.
