Along with the services Prime Technologies can offer, Planning & Validation Management services may include:
Terms:
GMP = Good Manufacturing Practices
QSR = Quality System Regulation
Why is equipment calibration a part of GMP/QSR?
- A manufacturer must develop and implement a quality system that assures all finished products meet the company's device/drug master record specs
- Assurance is obtained in many ways including the measurement of component, product and process parameters during design and production
What are the manufacturer's responsibilities?
To make sure that all production and QA test equipment, including mechanical, electronic, automated and chemical equipment are:
- Suitable for intended use
- Capable of producing valid results
- Operated by trained employees
- Properly calibrated vs. a suitable standard
What's included in the Procedures?
- Purpose and scope
- Frequency of calibration
- Equipment and standards required
- Limits for accuracy, precision and bias
- A description of the calibration process
- Remedial action
- Documentation requirements
Purpose and Scope:
Quality Assurance should determine which measurements are necessary to assure that device/drug design and process parameters are within established specifications for accuracy, precision and bias.
Frequency of Calibration:
- Depends on the type of equipment, the frequency of use and its criticality within the
manufacturing process
- Other factors which can affect equipment operation:
1. Temperature
2. Humidity
3. Contamination
4. Static electricity
5. Magnetic fields
6. Power Supply Fluctuations
Equipment and Standards:
- All equipment and standards used should be fully described in the device/drug master file or quality system records
- Environmental characteristics such as temperature, humidity, vibrations, and cleanliness must be considered when calibrating and using equipment
Equipment:
- Installation Qualification (IQ): action taken to assure that equipment and ancillary systems are properly installed, meet manufacturers' specifications and design intentions, operate appropriately in the intended range of use
- Operational Qualification (OQ): action taken to assure that equipment and sub-systems are capable of consistently operating within established limits and tolerances
- Performance Qualification (PQ): action taken to assure that equipment within a system is performing effectively and consistently over time
Equipment and Standards:
Where practical, standards should be traceable to the national Institute of Standards and
technology (NIST):
- Private standards are sent to NIST for calibration and returned
- NIST provides standard reference materials to be used in the calibration program
Limits for Accuracy, Precision and Bias:
- Accuracy: the measure of an instrument's capability to obtain the true or absolute value
- Precision: indicates the relative degree of repeatability
- Bias: a measure of how closely the mean value in a series of measurements approaches the true value
Remedial Action:
- Takes place when the limits are not met
- Should include the following provisions
1. Describe and initiate any action required to reestablish those limits (recalibration)
2. Evaluate whether there was any adverse effect on the device/drug quality
3. Document any actions taken and evaluations conducted
Documentation Requirements:
Paper system or software program:
- Equipment identification (including model number)
- Serial number
- Calibration date
- Calibrator's name
- Date of next calibration
- Calibration specs
- Address of mfr (optional)
- Reason for calibration (optional)
- Comments (optional)
- Outside service info (optional)
Calibration Personnel:
- Must be adequately trained through education and/or experience to perform calibration
- Should have a basic knowledge of metrology and calibration concepts
- Have an understanding of the basic principles of measurement disciplines, processing steps and acceptance requirements
- Knowledge of the overall calibration program
- Ability to follow instructions regarding maintenance and equipment use
- Conscientious attitude
Confirming Compliance:
- Audit of Calibration Program
Internal audits (required by QSR)
1. Maintaining a suitable schedule
2. Maintaining proper documentation
3. Suitable maintenance of standards
4. Adequacy of remedial actions
External audits
1. FDA considers contract laboratories an extension of a manufacturer's GMP
program so periodic are appropriate
2. Obtain documentation verifying that equipment was calibrated under controlled
conditions using traceable standards
Additional Concerns:
- Manufacturing equipment used in the production process (if automated) must be periodically calibrated
- Manufacturing equipment that is computer controlled must be validated for its intended use and be included in a calibration program
Addendum of definitions:
Installation Qualification (IQ):
Did you get what you wanted?
Do you have the proper facilities to use it?
Is all the equipment properly accounted for:
- Serial number
- Manufacturer
- In-house asset number
- Proper installation
- Instrument logbook in place
- Lab location
Operational Qualification (OQ):
- Documentation that verifies the lab equipment performs across anticipated ranges of use
- Series of functional tests to insure that an instrument/system is operating in accordance within the limits of a pre-determined set of criteria
Performance Qualification (PQ):
- Indicates that a specific set of method parameters is working properly in respect to the historic method validation
- In some cases System Suitability may be acceptable as Performance Qualification
Re-Qualification (RQ):
- Determination that an instrument, after repair, vendor service, location change, or adjustments have been made is operating as expected and intended
- Considerations
- Does instrument meet original protocols established?
- If not, what decisions need to be made?
