Qualification/validation can be defined as “establishing documented evidence which provides a high degree of assurance that specific equipment procured will consistently produce its predetermined specification and quality attributes”.
Validation was a term established by the FDA to obligate pharma/nutra companies to prove the control and reproducibility of their manufacturing process.
The FDA wanted industries to demonstrate statistically and with a scientific basis that the process was sound, reproducible and under control. Validation is intended to be the mechanism by which quality could verify manufacturing.
Qualification term is qualifying an equipment/system/utility/instrument based on URS. Validation comes in picture during the involvement of any parameters used to run the equipments/utilities/systems in as sequence.
Validation term is generally used for process validation and cleaning validation. Validation Master Plan (VMP) plays a significant role for equipments/utilities/ systems and instruments. It ensures that all processes and equipment affecting the quality, integrity, safety and efficacy of the pharmaceutical product are qualified and validated. All necessary activities and responsibilities for the qualification and validation are controlled and specified in VMP.
The life cycle of the qualification is divided into following steps: Project Validation Plan; (PVP). User Requirement Specification (URS); Design Qualification (DQ); Risk Assessment/Risk Management (RA/RM); Factory Acceptance Test (FAT); Site Acceptance Test (SAT); Installation Qualification (IQ); Operational Qualification (OQ); Performance Qualification (PQ).
Project validation plan
The commissioning of new facility, expansion or renovation (including addition or replacement of equipment which requires an alteration of facility or utility services) of existing facility shall be executed as per approved PVP initiated through change control.
User requirement specification
User requirement specification is to provide appropriate design and performance requirements for procurement of equipment/system/instrument/utility including major add-on component or major modification/expansion of area, to meet in house requirement as well as compliance with cGMP. The requirement for preparation of URS shall be evaluated at initial stage i.e. during procurement phase. The preparation of URS shall be applicable to the items intended for use as part of pharmaceutical/nutraceutical manufacturing and control and which impacts GMP.
Design qualification
Design qualification is to qualify hardware, functional and performance requirements for procurement of equipment/instruments/systems/utilities to meet in-house requirements, regulatory requirements as well as compliance with cGMP.
Design qualification is used as an initial activity before the equipments/ instruments/systems/utilities are purchased and installed. DQ defines the operational specification and performance requirement.
All the equipments/instruments/systems/utilities during DQ shall be evaluated for its impact on the product quality. The impact can be classified into three categories as direct impact/indirect impact and no impact. The equipment/instrument/system/utility on abnormal functioning impacts strength, identity, safety, purity and quality of product, have a direct contact with product or product component can be classified as direct impacting (product failure, risk or hazard level). The equipment/instrument/ system/utility that do not fall within direct impact or indirect impact categories will be classified as no impact. The equipment/instrument/ system/utility fall under this category can also be called as minor equipment/instrument/system/utility.
Risk assessment/risk management
Validation/qualification is to attain written evidence that processes and equipment work within their specifications to produce quality products.
Working with processes and equipment, there are always risks that may or may not be acceptable. To demonstrate whether or not possible risks are acceptable for the product quality, a risk assessment or quality risk management shall be performed.
It is to identify potential critical and non-critical points of the process or equipment. Risk shall be quantified using three dimensional risk scales like severity, probability and detectability. A risk probability number (RPN), shall be calculated based on these three factors. In case of RPN is beyond stipulated limit, a risk mitigation recommendation shall be made. A qualification matrix is to be prepared which shall indicate the process and parts of the facility for which assessment must be formed.
Factory acceptance test
Factory acceptance test is a way to ensure that equipment/system/utility being purchased meet the agreed upon design specifications. Ideally this happens before arriving at the customer’s site, however, for complex systems with high integration, tests may need to be performed at the customer’s location. Factory acceptance tests allows any issues to be corrected either at the vendor location or before operational qualification, leveraging the technical expertise and resources of the vendor preventing any potential cross-contamination with the customer’s site and improving the overall quality of the product delivered to the customer.
Site acceptance test
Site acceptance test is the stage where the customer conducts testing for the components supplied under the project scope and tests the conformance of the delivered resolution through the resolution definition document and functional specifications. SAT is performed at the site when the system is installed at the permanent operation position. The SAT is to test and check functionalities with other interfaces at the site. ISPE GAMP 5 defines SAT as a process that shows the system to be working as expected in its operational environment. The test show whether the system interacts correctly with all other systems at the site.
Installation qualification
As per FDA, installation qualification is defined as, establishing evidence that all key aspects of the process equipment and ancillary system installation adhere to the manufacturer’s approved specification and that the recommendations of the supplier of the equipment are suitably considered. IQ is to establish that the equipment/instrument/system/utility is installed and meets approved design specification and drawings and that they are properly interfaced with factory systems. It further details a list of all the cGMP requirements that are applicable to this precise installation qualification. These requirements must all be satisfied before the installation qualification can be completed and the qualification process allows progress to the execution of the OQ.
GMP requires that whatever approach is used, it is fully documented in the individual qualification documents. The IQ should not start with the FAT or commissioning tasks/SAT but it should start before these tasks are completed, enabling the validation team to witness and document the final FAT, commissioning testing/SAT. The integration of these activities greatly reduces the cost and time-consuming replication of unnecessary retesting. IQ shall cover minimal verification checks such as: Equipment design features; Installation and environmental conditions; Verification of all components parts; Material of construction; Safety features; Supplier documents, calibration, preventive maintenance and spare parts; and identify and verify that serial number and model number.
Operational qualification
Operational qualification can be defined as, the compilation of pragmatic evidence that a process can consistently produce regulatory controlled product to within predetermined specifications. OQ shall cover minimal verification checks such as: Determine process control limits with material specification; Determine potential failure modes, action levels and worst case scenario; Perform software qualification checks for intended use; Verification of alarms, Key functionalities; visual and audio display; Categorization of alarm into critical, major and minor; Verification of interlocks and permissive conditions; Standard operating procedure in place.
Performance qualification
As per FDA, performance qualification is establishing confidence through appropriate testing with document evidence that the finished product or process produced by a specified process meets all release requirements for functionality and safety and those procedures are effective and reproducible.
Performance qualification shall cover minimal verification checks such as: Approved procedures and limits from operational qualification; Acceptable product requirements; Simulate actual manufacturing conditions with actual parameters; and Define corrective actions if the system doesn’t meet the established criteria.
(Author is group leader, Strides Shasun Limited)