PACKAGE VALIDATION

Package validation involves two separate validations: 1) the design validation of the package as a component of the device and 2) the process validation of the packaging process. Design validation uses evidence to establish what design specifications will conform with the user needs and the intended use(s) . Process validation establishes by objective evidence that a process consistently produces a result or product that meets predetermined specifications.

The regulation refers to establishing evidence that the manufacturing steps involved in packaging the device will consistently produce packaging which meets specifications. For example, the process capability of packaging and sealing equipment should be determined during process validation and documented. Validation of the package design shall be performed under actual or simulated use conditions that show the package conforms to its stated intended uses. Risk analysis shall also be included where appropriate.

One of the most difficult aspects of package validation is determining how many samples to test. The goal is not to over test because of cost considerations while still running sufficient tests to provide statistically valid sampling.

PROCUREMENT, ACCEPTANCE, AND STORAGE

Manufacturers shall have adequate procedures for approval or rejection of all incoming packaging components such as adhesives, wrapping materials, corner protectors, pouches, cartons, etc. (820.80, discussed in Chapter 10). The supplier may test these components and provide the manufacturer with a protocol for testing and the test results for each batch (i.e., certificate of conformance to purchase specifications). The manufacturer could accept this specific data as sufficient certification based on his assessment of the supplier along with the review of the certificate or order his own testing.
Incoming components should be examined for damage and identity before being used. At a minimum, this examination should include visual inspection. Thereafter, the packaging should be handled and stored in such a way that it is kept clean and safe from damage. Packaging and devices to be sterilized should, obviously, be kept clean before sterilization. For transfusion and infusion assemblies, devices that come in contact with circulating blood or cerebrospinal fluid, intraocular lenses and the surgical instruments used in their implantation, and any device labeled as "pyrogen free" or "nonpyrogenic," the manufacturer should carefully and appropriately control the environment to which the associated packaging materials are exposed in order to minimize bioburden and cellular debris from dead bacteria. Pyrogens primarily arise from cellular debris of gram-negative bacteria.

PACKAGING PROCESS

The packaging operation is a manufacturing process. It is required to have adequate controls for components, processing, and test/inspection. The controls necessary for all devices should assure that:

• labeling, whether a separate label or printed on the package, properly reflects the package contents and other labeling requirements;

• the packaging materials meet the device master record specifications;

• only devices approved for release are packaged and released; and

• the packaging operations are performed according to established procedures.

The controls required will vary with the type of device packaged. For example, when a sterile device is packaged, a manufacturer's considerations should include:

• environmental and personnel hygiene control;

• validated operating procedures for sealing equipment;

• inspection to assure package integrity and sanitation; and,

• stringent control of packaged devices marked "sterile" but not yet sterilized.

For a product to be sterilized in-house, either a physical quarantine area or label control should be used to prevent shipment of devices marked sterile, but not yet sterilized. The required level of control is very high. The stringent control also extends to give-away samples not intended for actual use on patients -- samples should be sterile if so labeled because they might be used.

The device master record include packaging methods and processes.

The procedure for testing and/or inspection of finished packages shall be written .To the extent feasible, the testing of finished packages should be quantitative. The packaging of sterile devices should be tested and/or inspected before and after sterilization. This testing is done on a sampling basis. Sampling plans are valid only when a process is in a state-of-control; therefore, the device must be manufactured and packaged using a quality system as described in this manual