Process Validation SOP

SOP for Process Validation in Pharmaceutical Industry | Process Validation SOP in Pharma |

Process Validation SOP covers below points:
- Process Validation definition
- Purpose of Process Validation
- General principle to be considered for the process validation
- Process Validation is of four types:
  - Prospective
  - Concurrent
  - Retrospective
  - Re-validation
- Process Validation Protocol format
- Process Validation Report format

1.0 OBJECTIVE :

To define the Procedure of Process Validation for Tablet and Hard Gelatin Capsule dosage forms.

2.0 SCOPE :

This procedure is applicable to Process Validation of Tablet and Hard Gelatin Capsule products.

3.0 RESPONSIBILITY :

Quality Assurance Officer / Executive is responsible to prepare the Process Validation Protocol & Report. He / She is also responsible to perform the validation activity along with of Production, Quality Control, Warehouse & Engineering Personnel.
Quality Assurance Head is responsible to approve the Process validation Protocol & Report. It is the responsibility of Quality Assurance Department that this SOP is followed at the time of the process validation.
Validation Team is responsible for overall co-ordination & execution of Process Validation as per the approved protocol & also for the preparation of report with the help of production personnel.

4.0 ACCOUNTABILITY:

Q.A. Head

5.0 PROCEDURE :

5.1 Process validation is defined as the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products.

5.2 It is documentary evidence which will provide high degree of assurance that the process, by which particular product is manufactured and packed, consistently produce the product which meets predetermined specifications and quality attributes.

5.3 The general principle to be considered for the process validation during the manufacturing of the pharmaceutical products are as follows :

All Critical production processes are to be validated.
Validation studies shall be essential part of GMP and Validation Studies are conducted in accordance with pre-defined protocols (Refer Annexure No. 02). Written reports (Refer Annexure No. 03) summarizing recorded results & conclusions are prepared, evaluated, approved & maintained for 10 years.
A protocol is document that gives detail of agreed set of standard and test.
Changes to production processes, operating parameters, equipment or materials that may affect product quality and / or the reproducibility of the process are also to be validated prior to implementation.
A report summarizing recorded results and conclusions shall be prepared, documented and maintained.

5.4 During the processing of the validation batches, extensive sampling and testing should be performed on the product at various stages and should be documented comprehensively. Detailed testing should be done on the final product in its package. Also the stability studies are carried out on the validation batches.

5.5 Process Validation is of four types: Prospective, Concurrent, Retrospective and Re-validation.

5.6 Prospective validation: It is carried out during the development stage and/or on first three commercial batches on the basis of a risk analysis of the production process, which is broken down into individual steps; these are then evaluated on the basis of past experience to determine whether they may lead to critical situations.

During the product development phase the production process should be broken into individual steps. Each step should be evaluated on the basis of experience or theoretical considerations to determine the critical parameters of these factors. Each experiment should be planned & documented carefully in an authorized protocol.

5.7 All equipment, utilities, production environment & analytical testing methods to be used should have been fully qualified / validated. Final Master batch documents can be prepared only after the critical parameters of the process have been identified & machine settings, component specifications & environmental conditions have been determined. In the mean time the approved draft with limited validity are to be used.

5.8 Concurrent validation: It is carried out during the routine commercial scale production. Concurrent validation is carried out when a new product has been prospectively validated in manufacturing facility or there is a change in manufacturing process but the impact of change is not significant or there is a change in supplier of key Raw Material in existing production formula.

In this type of validation also all equipment, utilities, production environment & analytical testing methods to be used should have been fully validated. The justification for conducting the concurrent validation must be documented & the protocol must be approved by Quality Assurance Head.

It is generally acceptable that three consecutive batches within the finally agreed parameters, giving the product of the desired quality would constitute the proper Concurrent Validation. The necessary data can be taken from APQR.

5.9 Retrospective validation: Processes that are stable & in routine use & have not undergone a formally documented validation process is considered for Retrospective validation. Historical data may be utilized to provide necessary documentary evidence that the processes are validated.

The steps involved in this type of validation still require the preparation of protocol, the reporting of the results of the data review, conclusion & the recommendation.

Batches manufactured for a defined period (minimum of 10 last consecutive batches) or the numbers of batches release per year are used for retrospective validation. The necessary data can be taken from APQR.

5.10 Revalidation Criteria: Re-validation is usually performed to the confirmation of initial validation for a periodic review. Re-validation provides the evidence that changes in a process and / or the process environment that are introduced do not adversely affect the process characteristics & product quality. The requirement will be the same which is required for the process validation. Following are the examples of some planned or unplanned changes that may require re-validation.

Changes in raw materials physical properties such as density, shape, particle size distribution & moisture etc. that may affect the process or product.
Changes in the source of active raw material manufacturer.
Changes in container closure system.
Changes in the process, eg., mixing time, drying temperature & batch size.
Changes in the equipment.
Changes in the plant / facility.
Variations revealed by trend analysis eg. Process drifts.

5.11 Whenever necessary optimization batch can be planned to optimize the process. Process validation requirement is different for Tablet and Capsule, depend on the process and Critical Control Points.

5.12 The process validation is initiated & monitored by Quality Assurance department with the help of the individual department head & validation team members.

5.13 Different brand of same product (formula, process and batch size) will not be subjected for validation.

5.14 The process validation is carried out by validation team as per the process validation protocol.

5.15 Validation will be waived in case of + 10% change in batch size.

5.16 Process Validation for Tablet manufacturing:

Process Validation study of 3 batches manufactured by using same manufacturing process, under same environmental conditions, same Raw Material vendors and same manufacturing equipments is mandatory.

5.17 Process Validation for Capsule manufacturing:

Process Validation study of 3 batches manufactured by using same manufacturing process, under same environmental conditions, same Raw Material vendors and same manufacturing equipments is mandatory.

5.18 Validation Protocol :

A written plan stating how validation will be conducted, including test parameters, product characteristics, production & packaging equipment & decision points on what constitutes acceptable test results. The document should give details of the critical steps of the manufacturing process that should be measured, the allowable range of variability & the manner in which the system will be tested.
The validation protocol provides a synopsis of what is hoped to be accomplished. The protocol should list the selected process & control parameters, state the number of batches to be included in the study & specify how the data are assembled, will be treated for relevance.
In the case where a protocol is altered or modified after its approval, appropriate reasoning for such a change must be documented.
The validation protocol should be signed & dated by respective authorities & should contain the following minimum information :
- Objective
- Scope
- Responsibility
- Reference Document
- Procedure
- Product Details
- Product Composition
- Pre-Validation Requirement
- Equipment/Instrument Details
- Process Flow Diagram
- Description of critical and Non critical stages during processing
- Critical process parameter
- Process validation sampling plan
- Acceptance criteria
- Summary & Conclusion
- Schematic sampling plan from FBD
- Schematic sampling plan from octagonal blender
- Abbreviation used in the document

5.19 Validation Report:

When the validation is carried out, the actual data is recorded, compared with the requirement & acceptance criteria & a conclusion is made & authorized in the form of report.
The validation report should be signed & dated by respective authorities & should contain the following minimum information :
- Product details
- Analytical data
- Summary and Conclusion
- Recommendation
- Revalidation

5.20 The Process Validation Protocol should be numbered as follows :

For Tablet: QA/PVP/XXX/TAB/YYY/000
- Where; QA: Quality Assurance, PVP : Process Validation Protocol, XXX : Abbreviation form Product, TAB : Tablet, YYY : Three digit of Calendar year, OOO : Serial number of protocol.
For Capsule: QA/PVP/XXX/CAP/YYY/000
- Where; QA: Quality Assurance, PVP : Process Validation Protocol, XXX : Abbreviation for Product, CAP : Capsule, YYY : Three digit of Calendar year, OOO : Serial number of protocol.

5.21 The Process Validation Report should be numbered as follows :

For Tablet: QA/PVR/XXX/TAB/YYY/000
- Where; QA: Quality Assurance, PVP : Process Validation Report, XXX : Abbreviation for Product, TAB : Tablet, YYY : Three digit of Calendar year, OOO : Serial number of protocol.
For Capsule: QA/PVR/XXX/CAP/YYY/000
- Where; QA: Quality Assurance, PVR : Process Validation Report, XXX : Abbreviation for Product, CAP : Capsule, YYY : Three digit of Calendar year, OOO : Serial number of protocol.

6.0 ABBREVIATIONS:

Abbreviation	Expanded form
SOP	Standard Operating Procedure
Q.A.	Quality Assurance
Q.C.	Quality Control
QAD	Quality Assurance Department
GEN	General
APQR	Annual product quality review

7.0 ANNEXURES:

Annexure No.	Title
01	Process validation Protocol
02	Process validation Report
03	Process validation calculation sheet for dry mixing
04	Process validation calculation sheet for blending
05	Process validation calculation sheet for initial middle and final stage of compression
06	Process validation calculation sheet for compression (full, half and low hopper level)
07	Process validation calculation sheet for coating stage
08	Process validation calculation sheet for initial middle and final stage of capsule filling
09	Process validation calculation sheet for dried granules
10	Process validation Register