EQUIPMENT

NURUL HIDAYAH 08110110 16

INTRODUCTION
The Good Manufacturing Practices (GMP) regulation

requires that all equipment used to manufacture a device be designed and installed so that it can be adequately cleaned, serviced, and adjusted as necessary to maintain the equipment's accuracy, performance, and reliability.
The degree of maintenance of all equipment and

frequency of calibration of measuring equipment will depend on the type of equipment, frequency of use, and importance in the manufacturing process.

MAINTENANCE
Device manufacturers must maintain, clean, and

adjust equipment used in the manufacture of medical devices where failure to do so could have an adverse effect on the equipment's operation and hence the device. For example, failure to maintain, clean, and adjust a sealing and/or packaging machine used for primary packaging of sterile devices will eventually result in defective packages and thus nonsterile products.

If it is necessary to maintain, clean, or adjust equipment, the manufacturer must:

have a written schedule for performing these

activities; post the schedule or make it readily available; document the activities; where adjustment is necessary to maintain proper operation, post the inherent limitations and allowable tolerances of the equipment or make these readily available to personnel responsible for making the adjustments; and audit the activities and document the audit.

Records
As appropriate, maintenance records should be

maintained for each piece of equipment. Maintenance records and schedules are not needed for equipment such as lathes, presses, grinders, etc., that are used in a machine shop and maintained by skilled employ ees on a daily basis. Automated machining equipment will require maintenance schedules.

Equipment Selection

The purchase of stable and accurate measuring

equipment can reduce the frequency of calibration and increase confidence in the company's metrology program. Where economically feasible, equipment with more accuracy than needed for various measurements can be used longer without recalibration than equipment that marginally meets the desired accuracy requirements. Delicate instruments, however, that are "pushing the state-of-the-art" should not be used for routine measurements unless no other approach is feasible.

MANUFACTURING MATERIALS
Analyze Use The use of manufacturing materials that may adversely

affect the finished device should be carefully analyzed. Each process should be designed to use a minimum amount of adverse materials so as to reduce costs, reduce removal efforts, and increase the in trinsic safety of the device. Control Use the procedure used for routine cleaning of the device and its assemblies can be used for this purpose. If so, a special procedures is not necessary; however, when residues from such agents as ethylene oxide must be removed, special instructions usually are necessary.

AUTOMATED PRODUCTION AND QA SYSTEMS

The hardware system, software program and general quality

assurance system controls discussed below are essential in the automated manufacture of medical devices. The systematic validation of software and associated equipment will assure compliance with the GMP regulation; and reduce confusion, increase employee morale, reduce costs, and improve quality. Further, proper validation will smooth the integration of automated production and quality assurance equipment into manufacturing operations. Medical devices and the manufacturing processes used to produce them vary from the simple to the very complex, thus, the GMP regulation needs to be and is a flexible quality assurance system. This flexibility is valuable as more device manufacturers move to automated production, test/inspection, and record-keeping systems.

Software Validation Guidelines

The GMP regulation requires that software programs be

validated by adequate and documented testing when computers are used as part of an automated production or quality assurance system. Software used in automated production and quality assuranc e systems consists of programs or codes that cause computerized equipment to perform desired tasks, plus operator manuals and instructions. FDA has drafted general guidelines, "Principles of Process Validation" located in the appendix, that can be used wi th the GMP regulation to establish a software validation program. There are also standards, books, and articles that can be used for guidance. Military Specification MIL-S-52779A and the Institute of Electrical and Electronic Engineers (IEEE) "Standard fo r Software Quality Assurance Plan"

Formal Development of Software

The software should be appropriately structured and

documented so that any future changes can be accomplished, even by a different programmer, with a minimum of difficulty and maximum reliability.

To validate software, it must be: structured, documented and evaluated as it is developed; checked to make sure that it meets specifications; adequately tested with the assigned hardware systems; and operated under varied conditions by the intended operators

or

persons of like training to assure that it will perform consistently and correctly.

Validation of Equipment and Processes

Automated machine tools such as lathes, printed-circuit

drills and component inserters usually can be validated by conducting a first-and last-piece inspection of representative product lots. The record of this activity may be noted on the routine quality control or production records for the machine. Validation of complex microprocessor-controlled equipment, such as sterilizers, to verify satisfactory operation is generally a more extensive activity than the validation of machine tools. Typically, verification must be done by using a calibrated measurement instrument to check the actual parameters achieved during trial runs, and comparing these measurements with the setpoints and data outputs of the automated system.

Automated Data Collection and Processing

In addition to aiding the production of devices, computers

may be used to collect and maintain quality control and production records. These records are called the device history record in the GMP regulation. A device history is a compilation of records containing the production history of a finished device. When device history records or master records are maintained by computer, appropriate controls must be used to assure that data is entered accurately, changes are instituted only by author ized personnel, and records are secure. Hard copy or alternative systems such as duplicates, tapes, or microfilm should also be used to avoid losing records as a result of inadvertent erasure or other catastrophe. As appropriate, access to records and data bases should be restricted to designated individuals.

EQUIPMENT CALIBRATION
The GMP regulation is intended to help assure that

devices will be safe, effective and in compliance with the FD&C Act. To support this goal, each medical device manufacturer must develop and implement a quality assurance (QA) program that assures with a high degree of confidence that all finished devices meet the company's device master record specifications. These specifications should, in turn, reflect the company quality claims (see section 501(c), FD&C Act). Such assurance is obtained by many activi ties including the measurement of component and device parameters. These measurements must be made with appropriate and calibrated equipment.

 Each manufacturer must assure that production

equipment and quality assurance measurement equipment (mechanical, electronic, automated, etc.) are: suitable for the intended use in manufacture and testing of in-process and finished devices; operated by trained employees; capable of producing valid results; and properly calibrated versus a suitable standard.

CALIBRATION REQUIREMENTS
The GMP regulation requires that equipment be calibrated

according to written procedures that include specific directions and limits for accuracy and precision Precision has no unit of measure and only indicates a relative degree of repeatability, i.e., how closely the values within a series of replicate measurements agree with each other. Repeatability is the result of resolution and stability. Accuracy is the measure of an instrument's capability to approach a true or absolute value. Accuracy is a function of precision and bias. Because different manufacturers have different accuracy requirements, each manufacturer must decide the level of accuracy required for each measurement and provide equipment to achieve that accuracy.

GMP calibration requirements are:

routine calibration according to written procedures; documentation of the calibration of each piece of equipment requiring calibration; documented validation of the software programs used in automated production or quality assurance equipment; specification of accuracy and precision limits; training of calibration personnel; use of standards traceable to the National Bureau of Standards (NBS), or other recognizable standards; and provisions for remedial action to in-process or finished devices. Remedial action includes recalibration and evaluation of the impact of out-of-tolerance measurements on the quality of existing in-process or finished devices, and appropriate corrective action.

Procedures
A typical calibration procedure includes:

purpose and scope;

frequency of calibration; equipment and standards required; limits for accuracy and precision; preliminary examinations and operations; calibration process description; remedial action for product; and documentation requirements.

Personnel
The selection and training of competent calibration

personnel is an important consideration in establishing an effective metrology program. The GMP regulation requires that, "calibration shall be performed by personnel having the necessary education, training, and experience." Personnel involved in calibration should ideally possess the following qualities:

echnical education and experience in the area of job

assignment; basic knowledge of metrology and calibration concepts; an understanding of basic principles of measurement disciplines,

 data processing steps, and acceptance requirements;

ability to follow instructions regarding the

maintenance and use of measurement equipment and standards; knowledge of the overall calibration program; and mental attitude which results in safe, careful, and exacting execution of his or her dutie

Records
Calibration of each piece of equipment must be

documented to include the calibration date, the calibrator, and the date the next calibration is due. Many manufacturers use a system where each device has a decal or tag which contains the date of calibration, by whom calibrated, and date the next calibration is due. Examples of such decals are shown on the next page.
These decals are examples of the types commonly

used to identify the status of measurement instruments and tools. They are available as catalog

Schedules
Measuring instruments should be calibrated at

periodic intervals established on the basis of stability, purpose, and degree of usage of the equipment. Intervals should be shortened as required to assure prescribed accuracy as evidenced by the results of preceding calibrations. Intervals should be lengthened only when the results of previous calibrations indicate that such action will not adversely affect the accuracy of the system, i.e., the quality of the finished product.

Standards
Where practical, the GMP regulation requires that

standards used to calibrate equipment be traceable to the National Bureau of Standards (NBS), or other recognized standards. Traceability also can be achieved through a contract calibration laboratory whi ch in turn uses NBS services.

EQUIPMENT ENVIRONMENT
As appropriate, environmental controls must be

established and monitored to assure that measuring instruments and standards are calibrated and used in an environment that will not adversely effect the accuracy required. Consideration should be given to the effects of temperature, humidity, vibration, and cleanliness when purchasing, using, calibrating, and storing instruments.

AUDIT OF CALIBRATION SYSTEM

When a medical device manufacturer utilizes a

contract calibration laboratory, FDA expects the manufacturer to have evidence that the equipment was calibrated according to the GMP requirements. The manufacturer can do this by: requiring and receiving certification that the equipment was calibrated under controlled conditions using traceable standards; maintaining an adequate calibration schedule; maintaining records of calibration; or periodically auditing the contractor to assure

INTEGRATING MEASUREMENTS INTO THE QA SYSTEM

A good quality assurance program must include

calibration activities. However, proper calibration will be of little use unless the applications of the measurement equipment are properly developed and qualified during the preproduction development of insp ection test methods and procedures. As stated, effectiveness depends on the participation and influence of QA at the preproduction stage. Calibration of equipment cannot correct poor design of products nor can it compensate for poor applications of equipm ent and techniques. It is the continued use of a completed, integrated quality

EXHIBITS
Examples of calibration cards, decals, and cycle

cards were presented above in the text. Examples of a device cleaning procedure and a calibration procedure follow. Manufacturers may use these as presented if they match the firms operations; or may modify them to meet specific requirements.

P.C. Board Cleaning

This procedure covers the cleaning of printed circuit

boards by using an automatic washer. The procedure covers operation, shut down, cleaning, and routine maintenance.

Calibration Procedures for Mechanical Measuring Tools

his is a calibration procedure for mechanical

measuring tools, In actual use, the initial accuracy of each tool is checked using the procedure and is recorded. Thereafter, each tool is recalibrated (checked) versus the initial accuracy. Of course, the initial accuracy must meet or exceed the requirements of the measurements to be made with the tool. Precision is checked by making several measurements at various points on the tool's measuring face (surface).