A Standard Operating Procedure SOP for Validation Requirements: Responsibilities and Definitions pertinent to ensuring that processes, systems, or equipment meet predefined criteria for accuracy, reliability, and performance.

OBJECTIVE:

To define the responsibilities necessary for the successful completion of SOP for Validation Requirements: Responsibilities and Definitions program at ———-Pakistan facility.

SCOPE:

1. This policy applies to ——– manufacturing facility. It is the responsibility of ——— Validation Lead Team to assure that validation is completed.
2. ———- Pakistan believes that validation is the key element in assuring that the company’s quality assurance goals are met.

GENERAL REQUIREMENTS:

Product Validation:

a. The manufacturing of a new product is to be validated prospectively based on the process validation guidelines.
b. For existing products, retrospective validation may be used provided that the process has not been changed and demonstrates a successful history of process control.

Cleaning Validation:

Cleaning procedures require validation. In certain circumstances, as defined in the cleaning validation guidelines, the cleaning validation studies may be limited to most difficult products to be cleaned.

Equipment/Systems Validation:

1. IQ and OQ of the equipments used to support the manufacturing are to be validated based on IQ and OQ guidelines.
2. Automated control and monitoring systems to support production are to be validated based on their validation guidelines.

Air / Water Systems:

Air system, purified water and water-for-injection systems are to be validated based on their validation guidelines.

RESPONSIBILITIES:

Validation Lead Team:

1. Ensure that new products are validated prior to sale.
2. Ensure that the manufacturing processes are properly validated within a reasonable time as per validation guidelines.
3. Approve the validation protocol and reports.
4. Provide the necessary resources to conduct the validation.
5. Administer the change control program.

Engineering:

1. Execute the validation protocol for equipment qualification
2. Perform the IQ of the new equipments.
3. Perform the OQ of process equipment and systems, and then on regularly schedule basis and after repair.

Quality Assurance:

1. To organize the equipment calibration through outsource.
2. Conduct the required laboratory testing.
3. Review and approve the validation protocol and report.
4. Approve change control forms, as appropriate.

Validation Coordinator:

1. Develop and take the approval of validation protocol.
2. Maintain or organize records, files and necessary support documentation.
3. Coordinate with Validation team members for both Sterile and non-sterile validation program.
4. Prepare and approve take the approval the final validation report from Validation Lead Team.

SOP for Validation Requirements: Responsibilities and Definitions

 

DEFINITIONS:

Validation:

Establishing documented evidence, which provides a high degree of assurance that a specific process SOP for Validation Requirements: Responsibilities and Definitions will constantly produce a product meeting its predetermined specifications and quality attribute.

Validation Guidelines:

Validation guidelines developed by Validation group that serve as a guideline for conducting the validation studies.

Validation Protocol:

A written plan stating how validation will be conducted, including test parameters, product characteristics, production equipment, and decision points on what constitutes acceptable test results.

Validation Report:

The validation report presents the results of the validation

Process Validation:

Process validation is intended to verify by testing and following a written validation protocol that a process will reliably perform its purported function. Process validation studies are completed mainly on sterile products.

Product Validation:

Process validation is intended to verify by testing and following a written validation protocol that a product manufactured by a defined process will reliably applicable product specifications. Product validation studies are completed mainly on non-sterile dosage forms.

Validation Report:

The validation report presents the results of the validation

Cleaning Validation:

Cleaning validation is intended to verify measurement and testing that cleaning procedures, intended to minimize the risk of cross contamination of the identified product, achieves the purported function in a consistent and reproducible manner.

Calibration:

The comparison of a measurement standard or instrument of known accuracy with another standard or instrument to detect, correlate, report, and /or eliminate by adjustment any variation in the accuracy of the item being compared.

General:

1. Validation studies are conducted to determine the validity of significant production processes for each pharmaceutical product line or product group.
2. “Significant production processes” are those that could affect the identity, strength, quality, or purity of the drug product.
3. A “drug product line” or “drug product group” refers to those products that contain the same active ingredient(s) in a dosage form of similar processing parameters.
4. Validation / qualification studies may be performed by a combination of prospective, retrospective, and /or concurrent means.

Prospective validation:

Prospective validation is typically performed on new products and on existing products that undergo a significant formula or process modification. Normally it is performed on the first production batches (usually three consecutive lots) after the final batch size has been optimized. After procedure establishment, this approach is also used in the performance of cleaning validation studies and in equipment, utility and facility qualification studies.

Retrospective validation:

Retrospective validation is typically performed on existing products that have a large database. It is performed by statistically reviewing quality assurance release test data and batch record processing information form batches manufactured within a given period (typically the expiration date period of the product) and comparing these data with compendial or internal control specifications. It must include a history of rejected batches.

Concurrent validation:

1. Concurrent validation is a form of prospective validation usually reserved for low volume products, e.g. products made once per year. Further, it may be used for initial scale-up, in reworking lots, and in early operations of a continuous process.
2. Validation studies will proceed only after the preparation, approval and issuance of a written validation protocol.
3. A validation committee is to be appointed by Technical Director. This committee will be composed of members from Manufacturing, Quality Assurance and Engineering departments.
4. SOP for Validation Requirements: Responsibilities and Definitions
5. The validation committee is responsible for the design of the validation study and the preparation of the protocol.
6. Validation studies will proceed only after the preparation, approval and issuance of a written validation protocol.

Following are the steps of prospective process validation:

ACTIVITY RESPONSIBILITY

1. Preparation of Protocol Validation coordinator
2. Review and Approval of Validation Validation Lead Team QA Manager (For approval)
3. Qualification of systems and sub-system:
4. Installation Qualification Engineering
5. Operational Qualification Engineering, QA & Production
6. Calibration Engineering, QA
7. Protocol Execution Validation Coordinator
8. Sampling QA
9. Testing of samples QA
10. Preparation of validation report Validation Coordinator
11. Review and approval of validation report QA Manager
12. SOP for Validation Requirements: Responsibilities and Definitions
13. It is the responsibility of the above individuals to provide the necessary expertise and full support to the validation study.
14. Complete records of all validation studies will be maintained and permanently filed by the validation committee.
15. Results obtained from a given validation study will be summarized and reported by the validation Coordinator, and the approved report will be circulated as a support document for any changes required in the respective report for product specifications and /or standard operating procedure(s).
16. Each critical step in the process/procedure is validated /certified if it passes the acceptance criteria. Processing/procedural stages can be that and the subsequent stages will require validation/certification.

Acceptance criteria are determined as follows:

1. Process (Product) validation: Compendial or internal product control specifications.
   Cleaning validation: As described in cleaning validation protocol.
2. Equipment utility & Facility Qualification: Manufacturer’s specifications and/or company performance requirements.
3. Validation priorities are established based on the manufacturing volume associated with the product.

PROCEDURE:

Preparation of Protocol: A protocol is a document that gives details of equipment’s used in manufacturing, their operational qualification and calibration, parameters that should be measured e.g. RPM, with allowable range of variability details of manufacturing process with critical part like mixing times, moisture contents etc. The manner and locations from which the samples will be drawn and tested and their acceptance criteria.

Qualification of Systems & Sub-System:

1. In this phase each sub-system is qualified. To qualify, means to prove that the system does what it purports to do.
2. When a system is installed for the first time its qualification is done which is called Installation Qualification (IQ) may be defined as documented verification that all key aspects of the installation adhere to manufacturer’s recommendations, appropriate codes and approved design intentions. The IQ part encompasses such items as the suitability of the building. Services (air, water) the materials of construction equipment, and the suitability, positioning, accuracy and calibration of instruments.
3. Operational qualification (OQ) is a documented verification that the system or sub-system performs as intended throughout all specified operating range OQ covers investigation of control of the variables occurring with any piece of equipment or operation e.g. temperature distribution RPM etc.
4. Calibration of measuring devices may be treated as a form of qualification separately from IQ & OQ. Calibration may be defined as demonstrating that a measuring device produces results within specified limits of those produced by a reference standard device over an appropriate range of measurement. This SOP for Validation Requirements: Responsibilities and Definitions process results in corrections which may be applied if maximum accuracy is required. Measuring devices used for validation are calibrated both before and after validation work.
5. Engineering Department carries out qualification of systems and sub-systems.

Protocol Execution:

In this phase manufacturing process is carried out by production in Presence of Q.A. and R&D representatives. Initially all the ingredients are checked for weight and identified by verifying the materials labels and production order. Then the manufacturing is carried out exactly in accordance with manufacturing procedure, if it is required to make any changes in the process then the consent of R&D and Q.A. Manager is taken and changes recorded.

Sampling:

Samples for testing will be drawn as per protocol by QA department.

Testing:

Testing of the samples is carried out in accordance with latest approved monograph and acceptance criteria for composite samples will be release specification of the monograph and the acceptance criteria for individual positions will be same as described in protocol this is usually the content uniformity limit i.e. ± 15% of the added amount and a statistical limit (RSD) as defined in the protocol.
Note: If product is non-pharmacopeial then in-house specifications should be used.

Protocol Supplement:

If in the course of validation of two or three batches, it is observed that the results differ from expectation then a protocol supplement is prepared. Such practice provides a clear chronological history. A protocol supplement is a document, which explains a change to the original protocol, including reasons for its need.

Reviewing Validation Results:

Once validation execution is complete the data is reviewed /analyzed by Q.A and R&D, if required production Manager is also consulted. The results are reviewed after the manufacture of every batch if found satisfactory other batches will be manufactured with the same process. If the results are not found satisfactory then the analytical method/parameters/process/formulation shall be reviewed and the whole process of validation will be repeated in accordance with the supplement protocol.

Documentation:

After completion of test results, the Validation Coordinator prepares a report. A validation report is a scientific report of the results derived from executing a validation protocol. Validation report conclusions are a brief summary indicating the success of validation process and designating acceptable mean ranges that have resulted. QA Manager views the validation report and conclusions.

This SOP provides a structured framework for defining validation requirements, responsibilities, and procedures to ensure consistency, compliance, and reliability in validation activities across the organization.