Packaging Guidelines in 21 Code of Federal Regulations Part 211


As manufacturers of pharmaceutical products, pharmaceutical executives must know the appropriate guidelines governing the manufacture of packaging and labeling.

These requirements are stated in 21 Code of Federal Regulations Part 211.

Subpart G of 21 Code of Federal Regulations Part 211

Subpart G of these regulations includes the criteria for examining and using materials, issuing labels, using tamper-evident packaging for over-the-counter drugs, conducting packaging and labeling operations, inspecting drug products, and assigning an expiration date.

Under Subpart G, manufacturers should have written procedures that ensure that the correct labeling and packaging is used for a given drug product.

They should have features that:

• Prevent mix-ups and cross-contamination

• Provide clarification on how to identify and handle unlabeled samples that are set aside

• Enable identification of the manufacturing history of the batch through a lot or control number

• Specify procedures for examining packaging and labeling for suitability and correctness before packaging operations inspection of the packaging labeling facilities before use to determine that materials from other drug products have been removed.

The results of these inspections and examinations should be documented in the batch production record.


Manufacturers should provide written instructions and procedures regarding the examination and handling of materials. Any materials meeting the requirements may be approved, whereas those that do not may be rejected.

The importance of good recordkeeping

Records should be kept for any shipment of packaging that is received, regardless of whether it is approved or rejected. Labeling of each drug product should be stored separately and identified appropriately. Only authorized personnel should have access to the area where there are being stored. Outdated labeling should be destroyed.

Gang printing of labels is not allowed unless the labeling of the sheets is distinguished by size, shape, or color.

Cut labeling

If cut labeling is used, packaging and labeling operations should include one of the following: packaging and labeling lines specific to each individual strength of drug; use of appropriate electronic equipment to examine labels and packages for accuracy; visual inspection to examine the labels and packaging; or any other automated technique to determine that the labels are the correct size and shape. Printers should be monitored to make certain that the print matches that specified in the batch record.

Controls for drug labeling operations

Strict controls are in place for labeling issued in drug labeling operations. Labeling materials should be carefully inspected to determine that they are correct and that they conform to the labeling specified in the master batch of production records.

The manufacturers should have procedures to reconcile any discrepancies in quantities of the drug versus the quantity of the labeling produced. Manufacturers should destroy any excess labeling that has lot or control numbers.

If any labeling or packaging is returned, manufacturers should store it in a manner that will prevent mix-ups and enable correct identification. Manufacturers should have written procedures describing the issuing of labels, and all personnel should follow them.

Packaging for over-the-counter drugs

Packaging for over-the-counter drugs is also specified in 21 Code of Federal Regulations Part 211, Subpart G. Per Code of Federal Regulations Part 211, Subpart G, all over-the-counter drugs should be in tamper-evident packaging.

This package should have at least one barrier to entry that could indicate to consumers whether someone tampered with the drug.

The design of the package or the barriers should be distinctive. The barriers should have an identifying characteristic, such as an identifying name or logo, and the labeling should include a prominently placed statement that identifies the tamper-evident features and any capsule-sealing technology used.

The characteristics that make the packaging tamper evident, such as a sealed cap, should be identified on the label. Manufacturers can request an exemption from this requirement if they believe the requirements are unnecessary, cannot be achieved, or alternative measures can be taken to ensure safety.

They should also notify the Food and Drug Administration if they make any changes to their packaging or labeling.

Finishing operations

Packages and labeled drugs should be examined during finishing operations to ensure that packages and containers have the correct labeling. As such, a sample of the packaging should be collected and visually inspected, and the results should be recorded in the batch control or production records.

Drug packaging should also have an appropriate expiration date as determined by stability testing. Theses dates should also be described in relation to storage conditions stated on the labeling. Homeopathic products, allergenic abstracts that state "No US standard of Potency," investigational drugs, and over-the-counter drugs that have no dose limit and are stable for three years are exempt.

By knowing what the guidelines for packaging are, pharmaceutical executives can ensure that their facilities are manufacturing labeling and packaging that complies with the regulations. As such, they can manufacture packaging and labeling that complies with the appropriate standards for safety.

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