SUBJECT: Calibration of Instruments
7. FDA Regulations
Some specific GMP calibration regulations that address the pharmaceutical and device industries are:
CFR 21 Part 58 — Good Laboratory Practice for Non-clinical Laboratory Studies Section 58.63 — Maintenance and Calibration of Equipment
(a) Equipment shall be adequately inspected, cleaned, and maintained.
Equipment used for the generation, measurement, or assessment of data shall be adequately tested, calibrated, and/or standard.
(b) The written standard operating procedures required under Section 58.81(b) (11) shall set forth in sufficient details the methods, mate-rials, and schedules to be used in the routine inspection, cleaning, maintenance, testing, calibration and/or standardization of equip-ment, and shall specify remedial action to be taken in the event of failure or malfunction of equipment. The written standard operating procedures shall designate the person responsible for the perfor-mance of each operation, and copies of the standard operating procedures shall be made available to laboratory personnel.
(c) Written records shall be maintained of all inspection, maintenance, testing, calibrating and/or standardizing operations. These records, containing the date of the operation, shall describe whether the maintenance operations were routine and followed the written standard operating procedures. Written records shall be kept of non routine repairs performed on equipment as a result of failure and malfunction. Such records shall document the nature of the defect, how and when the defect was discovered and any remedial action taken in response to the defect.
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Current Good Manufacturing Practices for Finished Pharmaceuticals Section 211.25 — Personnel Qualifications
(a) Each person engaged in the manufacture, processing, packing, or holding of drug product shall have the education, training, and experience, or any combination thereof, to enable that person to perform the assigned functions. Training shall be in the particular
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operations that the employee performs and in Current Good Man-ufacturing Practice (including the Current Good ManMan-ufacturing Practice regulations in this chapter and written procedures required by these regulations) as they relate to the employee’s functions.
Training in Current Good Manufacturing Practice shall be con-ducted by qualified individuals on a continuing basis and with sufficient frequency to assure that employees remain familiar with cGMP requirements applicable to them.
Section 211.68 — Automatic, Mechanical, and Electronic Equipment (a) Automatic, mechanical, or electronic equipment of other types of
equipment, including computers, or related systems that will per-form a function satisfactorily, may be used in the manufacture, processing, packing, or holding of a drug product. If such equip-ment is so used, it shall be routinely calibrated, inspected, or checked according to a written program designed to assure proper performance. Written records of those calibration checks and inspections shall be maintained.
(b) Appropriate controls shall be exercised over computer or related systems to assure that changes in master production and control records or other records are instituted only by authorized person-nel. Input to and output from the computer or related system of formulas or other records or data shall be checked for accuracy.
A backup file of data entered into the computer or related system shall be maintained except where certain data, such as calculations performed in connection with laboratory analysis, are eliminated by computerization, or other automated pr ocesses. In such instances, a written record of the program shall be maintained along with appropriate validation data. Hard copy or alternative systems, such as duplicates, tapes, or microfilm, designed to assure that backup data are exact and complete and that it is secure from alteration, inadvertent erasures, or loss shall be maintained.
Section 211.160 — General Requirements
(a) The establishment of any specification, standards, sampling plans, test procedures, or other laboratory control mechanisms required by this subpart, including any change in such specifications, standards,
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sampling plans, test procedures, or other laboratory control mech-anisms, shall be drafted by the appropriate organizational unit and reviewed and approved by the quality control unit. The require-ments in this subpart shall be followed and shall be documented at the time of performance. Any deviation from the written spec-ifications, standards, sampling plans, test procedures, or other laboratory control mechanisms shall be recorded and justified.
(b) Laboratory controls shall include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling and drug products conform to appropriate standards of identity, strength, quality and purity. Laboratory controls shall include:
(4) The calibration of instruments, apparatus, gauges and recording devices at suitable intervals in accordance with an established written program containing specific directions, schedules, limits for accuracy and precision, and provisions for remedial action in the event accuracy and/or precision limits are not met.
Instruments, apparatus, gauges, and recording devices not meeting established specifications shall not be used.
Section 820.61 — Measurement Equipment
All production and quality assurance measurement equipment, such as mechanical, automated, or electronic equipment, shall be suitable for its intended purposes and shall be capable of producing valid results. Such equipment shall be routinely calibrated, inspected, and checked according to written procedures. Records documenting these activities shall be main-tained. When computers are used as part of an automated production or quality assurance system, the computer software programs shall be vali-dated by adequate and documented testing. All program changes shall be made by a designated individual(s) through a formal approval procedure.
(a) Calibration
Calibration procedures shall include specific directions and limits for accuracy and precision. There shall be provisions for remedial action when accuracy and precision limits are not met. Calibration shall be performed by personnel having the necessary education, training, background, and experience.
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(b) Calibration Standards
Where practical, the calibration standards used for production and quality assurance measurement equipment shall be traceable to the national standards of the National Bureau of Standards, Depart-ment of Commerce. If national standards are not practical for the parameter being measured, an independent reproducible standard shall be used. If no applicable standard exists, an in-house standard shall be developed and used.
(c) Calibration Records
The calibration date, the calibrator, and the next calibration date shall be recorded and displayed, or records containing such information shall be readily available for each piece of equipment requiring calibration. A designated individual(s) shall maintain a record of calibration dates and of the individual performing each calibration.
[The last GMP included in this listing is the original document that identified calibration program requirements but was never formally issued.]
CFR 21 Part 212 — Good Manufacturing Practices for Drugs Section 212.68 — Equipment Calibration
(a) Procedures shall be written and followed designating schedules and assigning responsibility for testing or monitoring the perfor-mance or accuracy of automatic or continuously operating equip-ment, devices, apparatus, or mechanisms such as, but not limited to, the following:
(1) Temperature-recording devices on sterilizing equipment (2) Temperature-recording devices on sterilizers
(3) Pressure gauges
(4) Mechanisms for maintaining sterilizing medium uniformity (5) Chain speed recorder
(6) Heat exchanger pressure differential monitor (7) Mercury–in–glass thermometer
(b) Written records of such calibrations, checks, examinations, or inspections shall be maintained, as specified in Section 212.183.
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Section 212.183 — Equipment Calibration and Monitoring Logs
Written records of calibration and monitoring tests and readings performed shall be maintained for at least 2 years after the expiration date of each batch of drug product produced by the equipment.
(a) Calibration records shall include (1) A description of the equipment
(2) The date the equipment was purchased (3) The operating limits of the equipment (4) The date, time, and type of each test (5) The results of each test
(6) The signature of each person performing a test (b) Monitoring records shall include:
(1) A description of the equipment (2) The date the equipment was installed
(3) The date the equipment was last calibrated, if appropriate (4) The operating limits of the equipment
(5) The date and time of the recording (6) The reading
(7) The signature of each person performing the monitoring (c) Corrective measures employed to bring the equipment into
com-pliance with its operating specifications shall be:
(1) Recorded in the appropriate equipment log (2) Noted in the calibration and/or monitoring record
(3) Immediately followed by testing to assure that the corrective measures were adequate to restore the required operating characteristics.
Section 212.192 — Production Record Review
The review and approval of production and control records by the quality control unit shall extend to those records not directly related to the manufacture, processing, packing, or holding of a specific batch of large volume parenteral drug product but which have a bearing on the quality of batches being produced. Such indirectly related records shall include:
(a) Those dealing with equipment calibration or standardization.
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REASONS FOR REVISION
Effective date: mm/dd/yyyy
First time issued for your company, affiliates, and contract manu-facturers
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