Inspections, Compliance, Enforcement, and Criminal Investigations
Guide to Inspections of Medical Device Manufacturers
Production and Process Specifications - Verify specifications and documented work instructions are provided for all processes in which variations could result in failure of the finished device to meet specifications.
Typical process examples are molding, heat treatment, welding, sterilization, blending, package sealing, solvent bonding, etc. Drawings may often be used for assembly, fabrication, etc. and in some cases training and workmanship standards may suffice in lieu of written procedures e.g., hand soldering.
Verify specification and procedure changes, and new specifications and procedures are reviewed and approved using a formal process and procedure. Changes in work instructions, drawings and other instructional procedures should also be made according to formal controls. Approval is often documented by using a standard form such as an Engineering Change Notice (ECN), Drawing Change Request (DCR), or other approval documents.
Reworking - Determine if devices or components are reworked during manufacture. Generally, routine reconditioning or repair prior to distribution is not considered reworking unless the activity would adversely affect the reliability, safety, or effectiveness of the device.
Routine replacement of defective parts would normally not be considered reworking, unless the structure of the supporting materials such as adhesives, epoxies, solders, etc., must be changed or modified. Replacing a defective plug-in circuit board would not normally be considered reworking. Replacement of integrated circuit chips where supporting material must be removed, replaced or modified would be considered reworking. Patching, regrinding, remelting, structure-strengthening, reheating, resterilization, etc., would also be considered reworking. If, in a reconditioning or repair process, the device is modified so that it does not conform to its original specifications, the activity then becomes remanufacturing.
Where reworking is not a routine part of the process, a high reworking rate may indicate production problems such as inadequate training or procedures which should be evaluated and corrected.
Verify written rework procedures are provided for guidance. In cases of routine rework, determine if the manufacturer has assessed the effect of reworking on the finished device or component and if the evaluation is documented.
Buildings - Facilities used for the manufacture, handling and storage of medical devices, components, or in-process material must provide adequate space designed to prevent mixups and to assure orderly handling of:
a. Incoming product (see definition of "product" 21 CFR 820.3(r))
b. Rejected or obsolete product
c. In-process product
d. Finished devices
f. Reworked or repaired devices
h. Molds, patterns, tools, records, drawings, blueprints
i. Testing and laboratory operations
j. Quarantined products
Environmental Control - Where environmental conditions at the manufacturing site could have an adverse effect on a device's fitness for use, these environmental conditions must be controlled to prevent contamination of the device. In general, this applies to the manufacturing environment and areas used for storage of product and the finished device.
Computers, computer components and software storage media may be sensitive to the environment especially in regards to temperature, humidity, electrostatic discharge (ESD), electromagnetic interference (EMI) and dust/dirt. Other products or finished devices may need to be handled or manufactured in a cleanroom environment to minimize bioburden. Written procedures are needed to assure the environment is controlled as required.
Verify there are documented inspections of these environmental controls that demonstrate the environmental control systems are properly functioning. Review of microbiological test results for air, water and surfaces are indicators on how well the environment is being controlled. Fluctuating results, or periodic spikes may indicate problems.