Section Twelve; Page 1 of 4

12PRODUCT EVALUATION

Section Twelve; Page 1 of 4

INTRODUCTION

Product evaluation is performed to show with documented evidence that a component, in-process unit, or finished device was manufactured according to the device master record (DMR) and meets all of the acceptance criteria/acceptance specifications in the DMR. The blank forms for recording the data become a part of the DMR. The emphasis in this chapter is on finished device evaluation; however, evaluation of incoming product and in-process units is conducted according to the same type of controls [820.80(a), 820.80(b), and 820.80(c)].

The GMP requirements for finished device evaluation are covered in section 820.80, which requires that the manufacturer establish and maintain procedures for finished device acceptance, to ensure that each production run, lot, or batch of finished devices meets acceptance criteria. Finished devices shall be held in quarantine or otherwise adequately controlled until released. Finished devices shall not be released for distribution until:

ºthe activities required in the DMR are completed;

ºthe associated data and documentation is reviewed;

ºthe release is authorized by the signature of a designated individual(s); and

ºthe authorization is dated.

Manufacturers shall also identify by suitable means the acceptance status of product, to indicate the conformance or nonconformance of these items with acceptance criteria. The identification of acceptance status shall be maintained throughout manufacturing, packaging, labeling, installation, and servicing of the product to ensure that only products that have passed the required acceptance activities are distributed, used, or installed (820.86).

If a manufacturer has adequate test and inspection procedures and these are used correctly by appropriately trained personnel, then there is a high probability that devices released for distribution will meet the company device specifications for acceptable product. Further, the data collected during in process or finished device evaluation should be appropriate, complete, and correct. This data shows the good and bad points about the product and specific production activities. The data may be fed back into the quality system to identify and solve real problems as well as to help maintain and improve the quality system.

Evaluation Specifications

In order to be assured that a device is fit for the intended use, a manufacturer should decide which characteristics of a device to test and/or inspect and to what detail or extent to test and/or inspect for conformance with the device specifications.

Decisions on what to test and how to test are made during the product and process development phase. For example, this decision is typically based on the:

ºintended use;

ºintended user;

ºnature of the device and its components;

ºintrinsic safety of the device;

ºreliability of the device;

ºoverall process capability of the manufacturing operation;

ºcharacteristics of test and inspection equipment and procedures; and

ºperformance margin of the device compared to the device specification.

Device test and/or inspection specifications, and test and/or inspection procedures, shall be carefully written and shall cover all appropriate points in the device acceptance specifications, in order to improve communication and reduce errors.

Design controls in 820.30(f) require device developers to verify the device design. Verification requires each manufacturer to write a test protocol and test, to the maximum feasible extent, all parameters of each device design against the design-input specification. (The design-input requirements become the input specifications at the verification stage of the development.) The verification test protocol includes the tests that will be performed on production units. Therefore, the production test procedures and some aspects of the inspection procedures are easily derived from the verification protocol.

Before the manufacturer is ready for full-scale production, the test and inspection decisions shall be completed, documented as test/inspection or acceptance procedures, and approved for use. It is a violation of the FD&C Act to place inadequately evaluated devices into commercial distribution. It is also a violation of the quality system regulation to allow test and inspection procedures to evolve during production, except during a highly controlled pilot-production phase. Further, devices that are not adequately evaluated may not meet company written or unwritten quality claims -- manufacturers cannot bypass their responsibility by simply not writing quality claims. Under Section 501(c) of the FD&C Act, a device is adulterated if its purity or quality falls below that which it purports or is represented to possess.

By the time the manufacturer is ready for production, the device specifications shall be supported by one or more test and inspection procedures documentation. These procedures are part of the DMR. To reduce drafting, filing, retrieval, and copying costs, test and inspection procedures may appear on process and assembly documents. Combination documents are commonly used for the fabrication and inspection/testing of subassemblies. There may be several test and inspection documents because evaluation may be performed at several in-process stages and at the finished device stage.

Although the manufacturer shall establish and maintain procedures for finished device acceptance, there are situations where a simple data sheet or blueprint may be referred to as the written acceptance criteria. For example, the acceptance of a simple molded or machined component or device may be determined by using a checklist, blueprint, or specification which specifies finished article dimensions, flash removal, etc. In machine-shop operations, a blueprint or engineering drawing may be used as acceptance criteria and used to meet the quality system written procedure requirements.

CORRECTIVE AND PREVENTIVE ACTION

GMP section 820.100 requires an analysis of problem data, returned product, and an investigation of non-conforming product. Also 820.198 requires an investigation of complaints that allege a device does not meet specifications. Section 820.100 refers to analysis of processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming or other quality problems. Section 820.198 also involves reviewing and evaluating complaints to determine whether or not an investigation is necessary. All these activities and their results shall be documented.

Some devices have a specified requirement for servicing. If this is the case, the manufacturer shall establish and maintain instructions and procedures for performing and verifying this servicing (820.200). The servicing reports shall also be analyzed using 820.100, Corrective and Preventive Action; if the servicing involves a death or serious injury, the service report is considered to be a complaint per section 820.198, Complaint Files, and is reported to FDA per parts 803 and 804, Medical Device Reporting.

The significance of the device and any hazard the defective device presents should be taken into consideration when determining compliance with corrective and preventive action requirements. Analysis shall be taken to the level necessary to determine the actual failure mechanism, e.g., defective component, incorrect raw material, erosion, composition, etc. The cause of failure is obvious in some cases and a formal investigation may not be needed. A record of the investigation, follow up, and conclusions shall be made in accordance with section 820.100.

When a systematic failure has been diagnosed, manufacturers need not analyze every device with the same diagnosed symptoms. However, enough devices should be analyzed to clearly establish symptoms before any assumptions are made about the cause of failure or about corrective actions. When an investigation results in identification of a deficiency, such as a failed component or a design flaw, and this deficiency may exist in other product lines, the investigation will not be effective unless it extends to determining the effect on other product lines.

If the failure is design related, the design shall be corrected per the design control requirements in 820.30 in order for the devices to meet company quality claims and not be adulterated under the FD&C Act section 501(c). When a failure is determined to be related to documentation, assembly, processing, labeling, testing, packaging, or other manufacturing operations, the manufacturing deficiency shall be identified, corrected, and documented.

REPACKER/RELABELER DEVICE EVALUATION

Finished devices received by a repacker/relabeler typically have been inspected and conform to specifications determined by the original manufacturer except for the final packaging and/or labeling. In most cases a repacker/relabeler would not have to assure that the finished device as received meets performance and configuration specifications. Finished bulk materials, such as dental resins, in vitro diagnostics, etc. may be accepted on the basis of a certificate of analysis for each batch.

Before releasing devices for distribution, repackers/relabelers should assure that devices are properly labeled (see chapter 11) and packaged (integrity, contents, etc., also see chapter 13). Often this can be accomplished using a list, illustration, or a model. When the packaged product will be sterilized or aseptically filled, written instructions and inspection/testing are necessary. Final acceptance of repacked/relabeled devices shall be recorded in accordance with 820.80(e). As noted, the final acceptance data is primarily related to correct labeling, correct packaging, and sealing of the packaging. In the case of aseptic filling operations, validation of the filling operations and finished device sterility testing are required.

NONCONFORMING PRODUCT

The manufacturer shall establish and maintain procedures to control product that does not conform to specified requirements. These established procedures shall include identification, documentation, evaluation, segregation, and disposition of nonconforming product. The evaluation of product non-conformance shall include a determination of the need for an investigation and notification of the persons or organizations responsible for the nonconformance. This evaluation and any investigation shall be documented (820.90). The manufacturer shall establish procedures for identifying the training needs of personnel who handle nonconforming products in the course of their work. These people should be trained to recognize product nonconformance and take appropriate action to control nonconforming products including identifying product as nonconforming, documenting and evaluating the nonconformance, and segregating and disposing of nonconforming product. This training should be documented (820.25).

To facilitate detection of failure or defect trends, internal problem data, including service reports, and complaints should be arranged in a way that permits correlating present and past data for a particular product or product line. This can usually be achieved by organizing files according to product or product lines. Such data may be maintained in a computer file for quick accessibility and analysis.

The manufacturer shall establish and maintain procedures that define the responsibility for review and the authority for the disposition of nonconforming product. Nonconformance may occur in-house, as well as before product is distributed, along with nonconformance of distributed product. Procedures shall set forth the review and disposition process. Disposition of nonconforming product shall be documented. This documentation shall include the justification for any use of nonconforming product and the signature of individual(s) authorizing this use [820.90(b)(1)]. The decision to use a nonconforming product is usually done by a material review board (MRB). MRB boards should operate according to a written procedure and be comprised of individuals having the knowledge to determine suitability for use of nonconforming product.

Each manufacturer shall establish and maintain procedures for rework, including retesting and reevaluation of the nonconforming product after rework, to ensure that the product meets its current approved specifications. Rework and reevaluation activities, including the determination of any adverse effects from the product rework, shall be documented in the DHR [820.90(b)(2)]

FAILURE INVESTIGATION

In order for a quality system to be self-correcting, data on quality problems from all sources should be fed back into the system. For example, complaints, service reports, and nonconforming products can provide valuable information that can point toward possible corrective actions. The more comprehensive a quality system is in taking preventive action, the lower the probability of customer dissatisfaction and the resulting need for corrective action. A true quality system has many preventive safeguards including GMP requirements for design, packaging, labeling, manufacturing control, installation, repairs, and complaint and failure analysis. A quality system that also covers the customer needs generally results in increased overall quality and greater customer satisfaction.

Service requests resulting from long use, misuse or accidental damage usually do not require corrective and/or preventive action. However, if service requests or other customer concerns are the result of rapid wear, unusual problems, unusual maintenance, or development of hazardous conditions, action may be necessary.

The manufacturer shall establish and maintain procedures for implementing corrective and preventive action. The procedures shall include the following [820.100(a)]:

ºAnalyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data. The purpose of the analysis is to identify existing and potential causes of nonconforming product, or other quality problems. Appropriate statistical methodology shall be employed where necessary to detect recurring quality problems.

ºInvestigating the cause(s) of nonconformities relating to product, processes, and the quality system.

ºIdentifying the action(s) needed to correct and prevent recurrence of nonconforming product and other quality problems.

ºVerifying or validating the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device.

ºImplementing and recording changes in methods and procedures needed to correct and prevent identified quality problems.

ºEnsuring that information related to quality problems or nonconforming product is disseminated to those directly responsible for assuring the quality of such product or the prevention of such problems.

ºSubmitting relevant information on identified quality problems, as well as corrective and preventive actions, for management review.

All these activities and their results shall be documented [820.100(b)].

EXHIBITS

Several forms for recording device production and evaluation data are briefly described below and then exhibited.

Portable Defibrillator Test Procedure

Ten pages extracted from a 31-page test specification for a family of portable defibrillators are reprinted below. This test procedure is long and detailed because a defibrillator is a complex device with a benefit to risk ratio that approaches infinity. This sample evaluation procedure covers final manufacturing, testing, and data collection performed by the production department to make absolutely certain that finished defibrillators comply with DMR specifications. This test procedure was developed based on the company approved device specifications.

To reduce errors and increase clarity, the test number column on the data sheet contains the paragraph number of the detailed requirements in the specification section of the procedure. The test equipment and schematics are not reprinted here.

Test DHR of a Printed Circuit Board Assembly

A data or "device history record" card for a printed circuit board is exhibited. The test procedure for the board is not reprinted. This data card is not the complete device history record for the finished device. When the finished device is tested, this board is tested again as an integral part of it.

Device History Record (urine plate)

A record sheet of the filling, labeling sample, inspection, and sample testing of a five-media urine plate is exhibited. Each activity is performed per procedure -- these procedures are not exhibited. The label record is an actual label as printed on the urine plates -- the record sheet is passed through the printing machine. This technique reduces costs and eliminates human copying errors.

Batch Production Record (XLD)

This exhibit is the batch production record of the XLD component used to fill one section of the five-part urine plate discussed above.

Batch Production Record (Thayer Martin)

This exhibit is a blank copy of the form used to record the batch production record for the Thayer Martin component used in the urine plate.

Batch Production Record (Blank form)

This exhibit is a form used to record the batch production record of various growth media. It could be used to record the production of XLD as mentioned above.

(Note: If any of these exhibits are required, refer to the original computer copy. Don)

Section Twelve; Page 1 of 4