VALIDATION

 VALIDATION

                                                                                                                                                   Deepak Garg

                                                                 M Pharmacy (Pharmaceutics)

VALIDATION

Definition:

Process validation is establishing documented evidence which provides a high degree of assurance that a specific process (such as the manufacture of pharmaceutical dosage forms) will consistently produce a product meeting its predetermined specifications and quality characteristics.

According to the FDA, assurance of product quality is derived from careful and systemic attention to a number of important factors, including: selection of quality components and materials, adequate product and process design, and (statistical) control of the process through in-process and end-product testing.

THE REGULATORY BASIS FOR PROCESS VALIDATION:

“There shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess.”

FDA regulatory officials established that there was a legal basis for requiring process validation. The ultimate legal authority is Section 501(a)(2)(B) of the FD&C Act [4], which states that a drug is deemed to be adulterated if the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or were not operated or administrated in conformity with CGMP.

Advantages…Process Validation

• Expanded real time monitoring and adjustment of process

• Enhanced ability to statistically evaluate process performance and product variables

e.g., individuals; mean; range; control limits

• Enhanced data and evaluation capabilities and increased confidence about process reproducibility and product quality

• Improved ability to set target parameters and control limits for routine production, correlating with validation results

• Enhanced reporting capability

Equipment validation

1.      Prepurchase or prequalification phase [ venders specification & design qualification]

2.      Post purchase or qualification phase [ installation, operational and performance qualification ]

3.      Routine or ongoing evaluation phase.

PREPURCASH PHASE

 Identified the bases functional requirement to defined type of equipment to fulfill their needs.

1. Vender specification

2. Design qualification

VENDER SPECIFICATION

1 .      Extent of resources and funds are considered what the vender previous experience in implementing similar projects.

2 .      The vender financial stability.

3 .      The level of training offered by vender.

4 .      Delivery time.

5 .      The vender familiarity with regularly requirement of equipment.

6 .      Vender documentation and support for testing.

 DESIGN QUALIFICATION

 Design qualification outline the prefecture of the system design of address the user requirement regulatory compliance and selection rational of a particular supplier. Design qualification is impact on installation, operational and performance qualification user and regulatory requirement should be demonstrated and documented.   

POST PURCHASE PHASE:

 INSTALLATION QUALIFICATION

Installation qualification aims to check documentation against reality. The result is “as-built documentation.” The other task in the IQ is to ensure that the GMP requirements are fulfilled.

Installation qualification is defined as “The performance and documentation of tests to ensure that equipment (such as machines, measuring equipment) used in a manufacturing process, are appropriately selected, correctly installed and work in accordance with established specifications.”

STEPS OF QUALIFICATION

INSTALLATION QUALIFICATION

Installation qualification aims to check documentation against reality. The result is “as-built documentation.” The other task in the IQ is to ensure that the GMP requirements are fulfilled.

Installation qualification is defined as “The performance and documentation of tests to ensure that equipment (such as machines, measuring equipment) used in a manufacturing process, are appropriately selected, correctly installed and work in accordance with established specifications.”

OPERATIONAL QUALIFICATIONS

Operational qualification is defined as “Documented verification that the system or sub-system performs as intended throughout all anticipated operating ranges.” Operational qualification tests whether or not the system works as expected. The approach to a successful OQ is the same as described for IQ , approve OQ protocols (by the quality assurance, production, and technical departments), perform OQ, work out OQ report, and approve OQ report (by the quality assurance, production, and technical departments).

Operational qualification of the control unit of a technical system is one of the most important steps during the OQ phase. It tests all critical functions and alarms of the technical system. The result of the OQ is a documented approval that the technical system fulfills the user requirements and all GMP-related functions of the technical system.

PERFORMANCE QUALIFICATION

The PQ is the phase in which either a technical system is tested over a long period of time (e.g., water system), or a complex technical system is tested overall (connected filling line). For many systems OQ is the last phase performed during qualification. If there are only a few performance tests needed, it might be more practical to include them during OQ or process validation.

Performance qualification should be executed by customer personnel. It is a great disadvantage if it has to be performed by the supplier. Ideally this phase allows know-how to be established at the pharmaceutical company. The following technical systems need to be performance-tested and quality.

High purity water systems (monitoring of the quality parameters: pH, conductivity, temperature)

HVAC systems (temperature, pressure, humidity)

Complex connected systems (e.g., filling line, performance parameters)

ROUTINE ON ONGOING EVALUATION PHASE

Instrument calibration involve measuring and adjusting the instrument record using non standard calibration is done at suitable interval and instrument not meeting established specification must not be use. Following points must be considered for calibration:

1.      Responsibility of personal involved in the calibration of equipment.

2.      Frequency of calibration for each type of instrument.

3.      Review and approval of calibration date.

4.      Procedure of issue of calibration stickers.

5.      Documentation requirement for calibration and report keeping.

6.      Reminder action in event of calibration failure.

7.      Procedure to notified user and obtained impacted assessment in case of calibration failure.

Requalification or change control

Relocation of equipment should only follow satisfactory review and authorization of the documented change proposal through changed control procedure.

Change control

It is a monitoring system which requires that a validated system remains validated by recognizing and addressed the potential impact of change of the system.