Qualification of Systems and Equipment in Pharmaceuticals

In the production of pharmaceuticals, there are many steps that must be completed consistently. A small issue with a piece of equipment or the utility system can greatly affect how products are made and cause products to be contaminated or rejected and cause pharma manufacturers to be out of compliance with regulations. For this reason, pharmaceutical manufacturers must complete qualification of all systems and equipment.

Qualification is the documented process that proves that systems and equipment have been designed adequately, installed properly, operated correctly and can continually perform to their originally intended use as indicated by their design specifications. Qualification of systems and equipment is required by the regulatory agency as a part of Good Manufacturing Practices and is therefore part of what makes up the pharmaceutical quality system.

What is Qualification?

The term Qualification refers to the proving process and the documentation that equipment, systems and utilities are fit for their intended use. The Qualification process documents the following:

• The equipment is installed correctly
• The systems operate correctly
• There is consistency and reliability in performance

Qualification is relevant for a number of different systems used in the production of pharmaceuticals, including:

• Manufacturing equipment
• HVAC systems
• Water systems
• Compressed air systems
• Analytical instruments
• Computerized systems

Importance of Qualification in Pharmaceuticals

The effect of the pharmaceutical product on the patient will impact the patient's health, therefore any pharmaceutical manufacturing process must be controlled with great care. Qualification will contribute to the following:

• Product Quality
• Process Consistency
• Equipment Failures
• Regulatory Compliance
• Reliability in Operations

Without the proper qualification, there can be no scientific assurance that the equipment will provide consistent performance.

Difference Between Qualification and Validation

Qualification and Validation are terms that sometimes get confused. Although the two have many similarities, they mean vastly different things.

Qualification

Qualification emphasizes the qualification of equipment, system, utility, etc.
Examples:

• Qualification of an Autoclave
• Qualification of HVAC Systems

Validation

Validation emphasizes the validation of processes and procedures.
Examples:

• Validation of a Process
• Validation of Cleaning

Qualification is the basis for Validation activities.

Qualification Life Cycle

The Qualification of Pharmaceuticals is completed according to a lifecycle methodology. Its completion consists of 4 phases of Qualification. The foundational phases of Qualification are:

• Design Qualification (DQ)
• Installation Qualification (IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)

Each of these phases confirms a different aspect of how a system or piece of equipment is suited for its intended use.

Design Qualification (DQ)

The primary purpose of Design Qualification (DQ) is to confirm that the proposed design of an equipment or system meets the following user and regulatory requirements. DQ's activities include the review of:

• Design specifications
• Engineering drawings
• Material of construction
• Capacity requirements
• Safety features

The intent of DQ is to ensure that the selected system will be appropriately qualified before proceeding to installation.

Installation qualification (IQ)

The installation qualification is a way to ensure that your piece of equipment or system was installed correctly according to the specifications that have been approved. The IQ activities include:

• Verifying that the piece of equipment has been installed properly
• Verifying that the utility connections have been made
• Verifying the instrument calibrations
• Identifying the equipment components
• Reviewing the manuals and documentation associated with the equipment

The purpose of the IQ is to ensure that the installation conformed to the engineering requirements and was good manufacturing practice.

Operational Qualification (OQ)

The operational qualification is an indication that the piece of equipment or system is working correctly and within established operating ranges. The operational qualification activities include testing the following systems:

• Controls and alarms
• Operating parameters
• Safety equipment
• Interlocks
• Start and stop procedures

The goal of the OQ is to ensure that the systems are working as expected.

Performance Qualification (PQ)

The performance qualification provides assurance that the equipment will meet process requirements when it is used for normal business activities on a continuous basis. The performance qualification activities include:

• Operation of the system while it is running normally
• Monitoring the system for a period of time
• Evaluating the consistency of the process

Performance Qualification will verify that the equipment is capable of supporting actual manufacturing operations, with a high probability.

Systems and Equipment Requiring Qualification

Several different systems are considered qualifying pharmaceutical systems.

1. Manufacturing Equipment

Examples of manufacturing equipment include:

• Mixing equipment
• Granulation manufacturing equipment
• Tablet compression manufacturing equipment
• Coating manufacturing equipment

Manufacturing equipment directly impacts the manufacturing of products.

2. HVAC Systems

HVAC systems within clean rooms maintain appropriate environmental conditions in clean rooms.
Qualification of HVAC systems ensures:

• Air flow
• Temperature of air
• Humidity of air
• Pressure differentials between the clean room and the outside environment

3. Water Systems

Water in a variety of water systems (purified water and WFI) will require qualification because water will be used widely in Pharmaceutical Manufacturing.

4. Compressed Air and Gas Systems

Compressed air and gas systems utilized in the production process will require qualification through established quality requirements.

The qualification process will provide assurance that compressed air and gases utilized in production will continue to be of the required purity and also will provide the reliability of consistent purity.

5. Sterilization Equipment

Examples of sterilization equipment will include:

• Autoclaves
• Dry Heat Sterilizers
• Depyrogenation Tunnels

These systems are essential to the sterile manufacturing process.

6. Analytical Instruments

Laboratory equipment, including HPLC and GC laboratory instruments, will require qualification to ensure that analytical results are accurate.

Qualification Procedure for Systems and Equipment

Performing qualification per documented procedure is an effective way to ensure successful qualification.

Step 1: User Requirement Specification (URS) Preparation

User Requirement Specifications (URS), which define the functionality, capacity and regulatory expectations of the System/Equipment, form the basis of Qualification activities.

Step 2: Risk Assessment

The Risk Assessment identifies critical functions and parameters that may impact product quality, in addition to establishing:
- Qualification scope
- Testing requirements
- Critical Operating Conditions

Step 3: Qualification Protocol Preparation

Qualification Protocols should define:
- Test scope
- Acceptance criteria
- Responsibilities
- Test Procedures
Protocols must be executed per approval prior to execution.

Step 4: Execution of Installation Qualification (IQ)

The installation of all components should be verified against approved specifications through the following:
- Equipment Verification
- Utilities Verification
- Calibration Status Verification

Step 5: Execution of Operational Qualification (OQ)

Operational Qualification (OQ) testing must be completed at all required operating conditions. Testing will include:
- Alarm Testing
- Temperature Mapping
- Speed Verification
Results of testing must meet defined acceptance criteria.

Step 6: Execution of Performance Qualification (PQ)

Performance Qualification (PQ) shall be completed while operating in routine conditions. Performance data will be captured and compared to confirm consistency during operation.

Step 7: Quality Assurance Review and Approval

The Quality Assurance department must review and approve all qualification data to ensure compliance with manufacturer’s specifications. Final reports of qualification are presented to the Quality Assurance department after all qualification data is reviewed and approved for compliance.

Documentation Requirements

It is essential that proper documents are completed throughout the qualification process. The following documentation is used most often as part of the qualification process:

• User Requirement Specification (URS)
• Risk Assessments
• Qualification Protocols
• Testing Data Sheets
• Qualification Reports
• Calibration Records

These documents demonstrate that Good Manufacturing Practices are being followed.

Acceptance Criteria

Acceptance criteria must be established and documented prior to starting the qualification process. An example of acceptance criteria is:

• Temperature Range
• Pressure Range
• Speed Limitations
• Alarm Functionality

Clearly defined acceptance criteria provide an objective basis for determining if the qualification systems are acceptable.

Requalification Requirements

Systems that have been qualified must remain in a qualified state for their entire life cycle. Requalification may be necessary after:

• Substantial Changes or Modifications to Equipment
• Equipment Relocation
• Repeated Deviations
• Preventative Maintenance on Critical Components

Periodic Requalification can also be scheduled.

Common Challenges in Qualification

There are a lot of problems an organization may encounter during the qualification process. Common problems that occur during qualification include:

• Missing Documentation
• Unclear Acceptance Criteria
• Limitation of Equipment Design
• Calibration Fails
• Poor Testing Methodology

Taking time to plan will help limit most of the above issues.

Risk-Based Qualification Approach

The modern method of qualification of pharmaceuticals follows the principles of risk management. According to ICH Q9 (Quality Risk Management), the systems that have a greater effect on the quality of the product will receive more thorough qualification efforts. Benefits of using a risk-based training approach include:

• The ability to better utilize the available resources
• Concentrating attention on the critical and most important systems
• Improving compliance

Best Practices for Equipment Qualification

The best practices that should be utilized are:

• Ur-Define your User's Requirements (URS) Before Purchasing
• Have cross-functional teams involved
• Utilize authorized Protocols
• Perform a complete review of the documentation
• Training for anyone using the product with regard to training & procedures

By utilizing these types of practices to improve the efficiency of qualification, you can also assist in improving compliance.

Quality Assurance's Role in Equipment Qualification

Quality Assurance (QA) maintains assurance the qualification of product through compliance and scientific soundness. QA is responsible for:

• Reviewing qualification protocol
• Approving qualification documentation
• Investigating deviations
•  Ensuring compliance of the product to the current Good Manufacturing Practice (cGMP) Guidelines

QA plays a major role in providing assurance that the integrity of the qualification will be maintained.

Regulatory Authority's Expectations in Equipment Qualification

Regulatory authorities expect pharmaceutical manufacturers to:

• Qualify the instruments, systems and material that are critical to the manufacturing process
• Maintain complete and up-to-date documentation
• Utilize a risk-based qualification approach
• Review and requalify critical equipment on a periodic basis

During an inspection, your qualification records will be thoroughly reviewed in order to verify compliance with all applicable regulations.

Benefits of Effective Qualification

A strong qualification program will provide the pharmaceutical organization with many operational advantages. The key advantages are:

• Increased Equipment Reliability
• Decreased Downtime
• Greater Consistency in Processes
• Reduced Risk of Contamination
• Increased Readiness for Regulatory Compliance

Properly executing a quality program that utilizes a risk-based approach will ultimately enhance the overall pharmaceutical quality system.

The importance of system and equipment qualification (also referred to as verification) in pharmaceutical manufacturing cannot be overstated since it provides assurance that the utility, equipment and system is appropriate for the intended application and will provide consistent support of the Product Quality for the totality of usage.

Pharmaceutical manufacturers are able to achieve Regulatory Compliance and operate efficiently by maintaining complete and well-structured qualification documentation, as well as utilizing risk-based qualification approaches during their qualification processes. The requirement for qualification is not only a Regulatory requirement in a highly-regulated industry, but also represent a critical part of Quality Assurance (QA) and Patient Safety.

Frequently Asked Questions (FAQs) on Qualification of Systems and Equipment

Q1. What is equipment qualification in pharmaceuticals?

Answer: Description of procedures used to qualify a piece of equipment or system so that it is appropriate to be used for the purpose intended.

Q2. What are the stages of qualification?

Answer: The steps involved are: Design Qualification (DQ), Installation Qualification (IQ), Operation Qualification (OQ) and Performance Qualification (PQ).

Q3. Why is qualification important?

Answer: The qualification of equipment is important because it results in the assurance of reliable equipment, consistent processes and compliance with regulations.

Q4. What is the purpose of IQ?

Answer: The purpose of IQ is to confirm that the installation of a piece of equipment or system has been performed correctly.

Q5. What is tested during OQ?

Answer: During OQ, testing of the operating parameters, alarms, controls and safety functions will take place.

Q6. What is Performance Qualification (PQ)?

Answer: PQ is the verification of ongoing performance during continued operations.

Q7. When is requalification required?

Answer: Requalification is necessary when a major modification or relocation is made to the equipment and/or following a significant maintenance event.

Q8. What do regulators expect during qualification?

Answer: During qualification, regulators will expect to see documented procedures, validation of protocols, testing activities and the supporting documentation required for Good Manufacturing Practices.

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