Guidelines on pharmaceutical packaging and labeling

Pharmaceutical packaging and labeling are an essential requirements for finished products in the pharmaceutical industry, and remain under tight scrutiny by pharma regulatory authorities worldwide. Packaging and labeling serve to retain and enable product efficiency and patient safety. To market and sell pharma products, a pharma product manufacturer must understand the relevant regulations to present its case effectively during the regulatory inspection and acquire a license to take out its product and sell to patients. 

As with other areas of the pharma industry, guidelines for packaging and labeling cover a broad aspect. It guides the technicalities and the physical appearance of labeling and packaging, focusing on patient safety and human health. Additionally, compliance with these regulations must be documented for proof to regulatory bodies during inspection.

Before diving deep into the guidelines, let's first discuss packaging and labeling in the pharmaceutical industry.

What are Packaging and Labeling?

Packaging refers to the container that contains the pharma product. It can take any form and shape according to the product requirements, provided they remain within acceptable limits. Its primary purpose is to protect the product from various external factors, such as heat & humidity, and deliver it to patients with the required therapeutic effects. It also facilitates product protection and safety in areas of extreme weather conditions, and during transportation of the pharma drug products. 

Besides protection, it also serves to identify and market the product. Different identification mechanisms can be used to help patients identify the correct medicines and prevent mix-ups with other medications. Packaging is also used for marketing purposes using various techniques. 

Commonly, three types of packaging material are used in the pharmaceutical industry: Primary, Secondary, and Tertiary. Packaging material that directly contacts the product's surface is called Primary, while packaging material that touches primary is called Secondary. After secondary, there comes the tertiary packaging, commonly used for transfer or shipping purposes.

Labels are briefed information in written and graphical form on a small paper. Paper material is selected carefully to suit climatic conditions and security mechanisms. It also ensure to prevent tearing or damage during the product life cycle. Its primary purpose is to provide critical information about the drug product that can include, but not limited to 

• Manufacturer detail

• Date of manufacturing

• Expiry date

• Product constituents

• Any other information necessary 

Now that we have briefly introduced packaging and labeling let's discuss guidelines for packaging and labeling.

Regulatory Guidelines

Some regulatory bodies issue guidelines for packaging and labeling, while others issue separate guidelines. Let's discuss them according to the United States and the European Union.

United States Food and Drug Administration - FDA

The United States FDA's guidelines 21 CFR part 211, "the policies related to Good Manufacturing Practices for Finished Pharmaceuticals", covers all the relevant details about the process involved. Its subpart G, "Packaging and Labeling Control," guides pharmaceutical professionals particularly about packaging and labeling. 

Following is the summary of various regulatory guidelines of the FDA about pharma packaging

CFR 211.122 - Material Examination and Usage Criteria

• A written Procedure for receipt, identification, storage, handling, sampling, examination, and testing shall be followed.

• Only those packaging and labeling materials that meet written specifications shall be approved and used. If they do not meet these specifications, they shall be rejected to prevent them from being used in operations.

• Record of each shipment (for packaging material and labels) shall be maintained, including receipt, examination or testing, and pass/fail. 

• Labels (and relevant materials) for different drug products, strength, and dosage forms should be stored separately with suitable identification. Only authorized persons can access the store where materials have been stored.

• Outdated labels shall be destroyed

• Gang-printed labeling is prohibited unless printed sheets are differentiated by size, shape, or color.

• Printed devices with manufacturing lines shall be monitored for conformance with batch production records

CFR 211.125 labelling Issuance

• The manufacturer is responsible for strict control over issuing labels. 

• When issuing, labels must be carefully examined for conformity against batch production records

• Reconcile procedures should be applied for issued, used, and returned labels. If discrepancies are found, they must be thoroughly investigated by 21 CFR 211.192.

• Excess labels bearing lot number  should destroyed

• Returned labels should be prevented from being mixed up with proper identification.

• Procedures for issuing labels should be defined and written, and must be followed strictly

211.130 packaging and Labelling Operations

This provides guidelines for executing packaging and labeling operations in a pharmaceutical facility. It focuses on written procedures for executing such operations, and it should contain the following information

• Such operations should be physically and spatially separated from other operations

• Unlabeled products that are filled and ready for labeling must be appropriately identified and handled to prevent mislabeling. These must be provided for each container

• History of manufacture and control must be included in the identification procedure

• Examination procedure of each packaging and labeling material before their relevant operations should be developed and followed. Such procedures must also become part of the batch production record

• Before the start of relevant operations, inspections to confirm products from the previous batch have been removed. Additionally, it should include removing non-suitable label material from the area. 

CFR 211.132 Tamper-evident packaging requirements for over-the-counter (OTC) human drug products

This section describes ways to apply tamper-evident packaging to improve the security of drug products.

• Each manufacturer of pharma drug products should package the drug product in tamper-evident packaging by 

• Having one or more indicators or barriers indicating evidence of tampering. 

• Such package must not be duplicated with available materials by using a pattern, name, logo, or picture

• Involving immediate container and closure system indicating visual integrity of the package. 

• Such measures should remain intact during manufacturing, distribution, and retail display

• The two-piece acceptable tamper-evident mechanism must seal the two-piece hard gelatin capsule

·The label should

• Identify tamper-evident features or capsule-sealing technology

• It should be prominently placed on the pharma drug product

• Labels should remain safe if tamper evident mechanism is breached

• Tamper evident mechanism should be indicated in the labeling statement

Procedure for requesting exemption from packaging and labeling

A request for exemption should be submitted as a citizen petition. The envelope should be identified as "Request for Exemption from the Tamper-Evident Packaging Rule." The information in the petition should contain the following

• Name of the drug product. If it is a drug class, name of all products in the specified class

• Reasoning that compliance with tamper-evident is unnecessary, or if it cannot be achieved

• Alternative steps, if available. Or, if the manufacturer has taken other steps, details of such steps

CFR 211.134 Drug product inspection

This section explains the Procedure for product inspection during different stages of pharm drug manufacturing cycle

• Finished products during packaging and labeling operation should be inspected to ensure appropriate labeling of containers and packages

• Sample units should be collected after the final finished operations and examined for correct labeling

• Results of the inspections mentioned above and examinations should be included in batch production records

CFR 211.137 Expiration dating

This section guides the expiry date labeling of a pharma drug product

• The product should bear the expiry date (determined through stability studies) to ensure product adherence to the standards of identity, strength, quality, and purity

• Expiry dates related to storage conditions must be determined through stability studies

• For the drug products that required reconstitution at the time of dispensing, the expiry date for both reconstituted and un-reconstituted should be mentioned on the label

• Homeopathic drug products are exempt from the requirements stated in this section. Additionally, allergic extracts labeled as "No U.S. Standard of Potency" are also exempted

• New investigative drug products are also exempted from this section, provided they follow relevant standardization procedures.

• Requirements of this section will also not be applied for OTC products pending proposed consideration, as published in the Federal Register on September 29, 1978, if their labeling does not include dose limitation and are stable for at least three years.

World Health Organization - WHO 

World Health Organization - WHO is also a pharma regulatory body with an international perspective. Some packaging and labeling guidelines according to WHO are mentioned below

The WHO guidelines are known as Annex 9 - Guidelines on packaging for pharmaceutical products. Some highlights of its guidelines are described below

• It mentions some essential types of raw material for pharma packaging, including cardboard, paper, glass, plastic, and metal. Additionally, it introduces and describes primary, secondary, and tertiary packaging material.

• It describes functions of packaging as containment, protection, presentation & information, compliance, and counterfeit detection

• It also describes the classification for each packaging type, such as glass, plastics, and metals. 

• Quality assurance aspects are also discussed and include

• Regulatory regulations

• Product

• Production process

• Manufacturer's internal policies

• Quality Control is divided into 

• Sampling

• Testing program, including 

• Visual inspection

• Material testing

• Dimensional testing

• Physical test

• Chemical test

• Microbiological test

• Inspection and audit. Some guidelines that this section provides include

• Rules

• Audits of suppliers

• Environmental protection by repackaging waste and waste policies

• It also describes pharmacopeia requirements related to international, United States, Europe, and Japan, and includes

• Packaging material

• Requirements for dosage from containers

• Glass containers

• Plastic containers

• rubber closures

About The Author

Muhammad Asim Niazi

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.