Labeling of Medical Devices from the standpoint of GMP / QMS

Labeling includes all labels and any written, printed or graphic matter on the device or container or wrappers or anything accompanying such device. Label control and labeling content are the two main aspects of labeling. Label mix-ups, product mix-ups, label printing errors, label versus container errors, wrong inserts or outserts are the most common labeling mistakes.

Labeling Development

A literature search should be conducted for all new labeling content development. These retrieved literature articles may serve as documentation for labeling claims. Rigorous scientific evidence of efficacy is required before including the indication in the package insert. The indications for use may be obtained from adequate and well-controlled clinical study or may be derived from scientific literature or personal communication with the physicians. During the determination of adverse effects the cause of the adverse effects should be carefully evaluated by the label writer. Many implantable devices have the adverse effects which are not related to the devices per se but are attributable to the surgery. In such cases it would be helpful to include a disclaimer stating that the following effects have been noted which may or may not be related to the device and the adverse events may be listed after that.

A statement regarding sterility should be given, wherever necessary. Instructions to open the package containing sterile devices without contamination may be provided in the label. Also if the device is single use sterile device, suitable warning should be given to advice against re-sterilization or reuse. The failure to warn of product dangers can result in product liability suits by injured persons. Investigational medical device may be labeled with “Caution: Investigational Medical Device”.

To avoid any misunderstanding of the labeling it has to be written with the target audience in mind. Pretesting of the labeling for user comprehension can be done using focus group interviews, individual interviews and readability testing. Patient labeling should include the information which is appropriate for the patient in laymen’s language. Combination labeling is directed towards both the physician and patients. It would be beneficial for the patient, as it supplements the oral instruction already received from the physician.

A new label should be developed after discussing with the packaging department as they provide the inputs regarding the label like the size of the insert, the type of paper, number of folds, etc, which are vital in the preparation of label. After which it should be circulated to other departments like marketing, legal, medical and engineering and finally returned to the label compliance manager. It was then edited and sent to the printing department. The printed label should be legible during the lifecycle of the device.

Label Control

Label control is the function of the quality control department and it should be handled only by an authorized personnel. Labeling is part of the device master record and hence any change in the labeling must be made under the formal change control procedure.  The content and physical design parameters of labels, like engineering drawing, artwork, inspection or control procedures, and procedures for attaching the label, should be specified in the device master record. Printing of the label should be done in accordance with the engineering specifications like label substrate, dimensions, ink and finish. The label should be proofread for accuracy before the printing, and before issuing it. 

Adequate controls should be in place to prevent the labeling mix-ups. The labels should be properly stored and maintained in a manner to avoid mix-ups. The issued labels may be double counted and a specimen label should be maintained for future reference. The manufacturer should keep complete records of labeling procedures, including the labeling changes, as well as copies of all approved labels. The labeling process should be evaluated by appropriate simulations or by performing the actual process. It ensures the label is appropriately designed and assures that it is legible under the normal conditions of use and also during handling, storage and distribution of labeling.

To avoid mix-ups and other labeling errors the following procedure may be adopted:

1. Labeling and packing operations should be carried out in an area having sufficient space.
2. The labeling area must be inspected prior to the labeling to ensure that it is free from extraneous devices and labeling materials from the previous operations.
3. Any such items found must be disposed off appropriately, as per the standard operating procedure.
4. Accesses to labels should be restricted to authorized personnel.
5. The issued labels may be examined for identity and accuracy.
6. The record of such inspections and the designated individual who performs such inspections along with the date and time should be maintained in the device history record.
7. Labels are stored in a manner that provides proper identification and avoids mix-ups. Care should be taken for sterile and not yet sterilized devices mix-up.
8. Multiple labeling operations must be separated to avoid the mix-ups.
9. The finished device should be inspected as per the written procedure.
10. Reconciliation is recommended for the number of labels.
11. Critical devices may also contain a control number for tractability.

The major factors that contribute to the product mix-ups are use of cut labels, labels which are similar in color, size and shape, and poor label control procedures. Proper training of packing line and label control employees about the serious consciousness of labeling errors helps to avoid product mix-ups.