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EMC MDQS Page 22

Guide to Inspections of Medical Device Manufacturers
December 1997

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Quality System Record (QSR) - The QSR must include, or make reference to the location of, the procedures and documentation required by the QS/GMP that are not specific to a particular type of device. This includes all procedures and records required by 21 CFR 820.20, Management Responsibility. It may also include general procedures for complaint handling, cleaning, maintenance, etc. The QSR should be prepared and approved as required by 21 CFR 820.40, Document Controls.

It is not important in which record, DMR or QSR, a particular procedure or document is included. It is more important that the manufacture have the procedure or document and that it is readily available for our review.


Pre-Approval inspections are confined to PMA and Class III 510(k) devices. The purpose of these inspections is two-fold:

  1. Verify that the information submitted with the particular 510(k) or PMA in regard to manufacturing is accurate. (i.e. Does the firm have the equipment, personnel, facility, etc. to manufacture the device under review? Are they complying with the product or process specifications listed in their application?)
  2. Assess the firm's ability to meet the Quality System/GMP Regulation.

If any changes to the application have occurred, it should be determined whether these changes have been adequately communicated to the appropriate reviewing staff in CDRH/Office of Device Evaluation.

See Compliance Program 7383.001 for further instructions on doing device pre-approval inspections.


If the firm is manufacturing sterile devices, CP 7382.830A, Attachment A, must be followed.

There should be records to show how the sterilization process was validated. ANSI/AAMI/ISO Standards are published for the major sterilization processes and can be used for guidance in the evaluation of the process validation. If a firm applies the ANSI/AAMI/ISO standards appropriately and follows them in validating a sterilization process, CDRH will be satisfied with the approach. However, a firm is NOT required to follow these standards. They may choose to validate their sterilization process using some other method. If they do, they will need to explain the scientific validity of the method they used. Obtain appropriate records to document any deficiencies related to validation.

A determination should be made as to whether the firm is or may be producing nonsterile devices. There are several ways of making this determination:

  1. Review lot release records and sterilization process records that show what the cycle parameters or absorbed dose were for each of the lots released. Compare those parameters to the validated cycle parameters. All of the released lots should have met the validated cycle parameters. If any lot did not meet the validated cycle parameters an investigation should have been made. If any of the nonconforming lots were released, they may be non-sterile.
  2. Review the firm's bioburden data to identify the type and resistance of the bioburden on the device. If the cycle used is bioburden based then the cycle must be able to demonstrate that the appropriate sterility assurance level (SAL) has been obtained prior to release of the sterilized lot. Be aware of seasonal fluctuations in the type and amount of bioburden which can be found on the devices before sterilization.
  3. Review the firm's current product and packaging to determine if it is the same as that used for the validation of the sterilization process. Changes in the packaging materials need to be evaluated and may require revalidation.

The SAL is the probability of a unit being nonsterile after exposure to a valid sterilization process. The SAL varies according to the intended use of the device. Sterilized articles not intended to contact compromised tissues are generally thought to be safe for use with an SAL of 10-3; that is, a probability of one nonsterile unit in a thousand. Invasive and implantable devices should have an SAL of 10-6; that is, no more than one nonsterile unit in a million. In practice, many firms use overkill cycles which assure an even lower probability that a device will be nonsterile.

Review the firm's investigation reports for any lots that had positive sterility test results and/or positive biological indicator (BI) results.
Review the firm's records to determine if any reworking (resterilization) procedures were performed due to process failure.
The firm's validation reports should include adequate data to assure device performance and package seals were not adversely affected by any reworking.

Test methods in use should be based on accepted test methodologies. The tests should be performed properly so as to be able to detect positive sterility/BI test results. If an in-house test method is used, it should have been validated to show it is as capable of detecting nonsterile units as readily as referenced methodologies.

If reworking (re-sterilization) was performed, it should be documented and be permitted per the firm's validation data. Verify the resterilized lots were adequately reworked, and were properly tested prior to release. The firm should have conducted a failure investigation prior to release to determine why the initial test results were positive.

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