Pharmaceutical packaging plays a critical role in ensuring the safety, efficacy, and quality of medications. The US Food and Drug Administration (FDA) closely regulates packaging and labeling, as well as manufacturing processes in pharmaceutical packaging. Ultimately, these regulations and guidelines safeguard patient health.
The Role of FDA Guidelines in Pharmaceutical Packaging
The overarching regulatory framework for prescription drug packaging is laid down in the Federal Food, Drug, and Cosmetic Act (FDCA). This is implemented in Title 21 Code of Federal Regulations (21 CFR). Labeling is covered in 21 CFR Part 201, with related guidance, such as “Instructions for Use – Patient Labeling for Human Prescription Drug and Biological Products — Content and Format,” [1] and Labeling for Human Prescription Drug and Biological Products – Implementing the PLR Content and Format Requirements [2]
What do the regulations cover?
FDA regulations and guidelines cover:
• Primary packaging: packaging that comes in direct contact with the drug (e.g. blister packs, vials, bottles, etc.).
• Secondary packaging: cartons, inserts, shrink wraps, space for branding and mandatory product information (e.g. package inserts). These are designed to prevent direct contact with the medication.
• Tertiary packaging: generally, for bulk transportation in the supply chain.
Artwork mostly falls within the category of secondary packaging, because this is where product names, logos, barcodes, patient package inserts, medication guides (MedGuides) and instructions for use are found (although tertiary packaging does have barcodes and some functional artwork). The greater focus of FDA regulations is therefore on secondary packaging. Tertiary packaging is generally covered in cGMP. [3]
Packaging Artwork: A Critical Component
Packaging artwork is a critical component that has overlapping aesthetic, functional and regulatory features. Non-compliant artwork poses a risk to patient safety and may lead to a warning letter from the FDA, a product recall, and possibly legal and litigation costs. Ultimately, this impacts the availability of the treatment and return on investment. As in other industries, packaging artwork goes far beyond pleasing the eye. But in pharma, the risks are higher if you don’t get it right.
What is packaging artwork?
Just some of the features or elements of packaging artwork are:
• Branding elements: Logos, colors, and fonts that distinguish your company’s products.
• Regulatory information: Patient and prescribing information, active ingredients and inactive ingredients, warnings, expiration dates required by the FDA, mandatory or optional barcodes, and more.
• Design elements: Layouts, typography, and images, diagrams and tables that make the information clear and readable.
• Security features: Product identifiers as part of the Drug Supply Chain Security Act (DSCSA) [4], holograms, and tamper-evident elements.
Compliance Considerations for Artwork
As mentioned earlier, the risks associated with non-compliance in the pharmaceutical industry are high.
Regulatory compliance
It all begins here, and it is essential that you understand the current regulations and guidance. Understanding regulations on labeling, supply chain security, and promotional materials [5] [6] are just the tip of the iceberg, because of the many forms and requirements for packaging. Change control processes for compliance must also be in place, because regulations and guidance are evolving.
Accuracy and consistency
Your packaging artwork must be accurate, or you will face the regulatory and legal consequences. Consistency includes across different packaging formats (physical and online), dosages, different markets or territories, languages, regions, and more. Having processes in place to use approved standard wording, while developing and applying clear brand and other internal guidelines helps. Leveraging technology is crucial here; we discuss this later.
Design, print specifications and readability factors
• Font size and contrast is important for readability. Follow FDA readability guidance [7] Also see some best practices in our article here [8].
• Use high-contrast colors and proper spacing to enhance clarity and minimize confusion.
• Image and print quality must be sufficient to ensure accurate reproduction of essential labeling information.
• Braille inclusion is not mandated by the FDA, but companies may include it voluntarily to improve accessibility.
• Digital artwork must follow a structured reading order to support text-to-speech software, ensuring accessibility for blind and visually impaired patients.
• Barcodes and serialization. Barcodes, depending on their type, (including QR codes) must conform with ISO or GS1 standards. They must be readable and may link to approved electronic labeling resources.
Approval, review and update workflows
We look into this in detail below.
Common Challenges in Meeting FDA Guidelines
Artwork revision errors
Because pharmaceutical packaging artwork goes through multiple revisions before final approval, each change must be carefully managed to ensure accuracy, consistency, and compliance with FDA regulations. Some common issues in the revision process are:
• Version control and update: With multiple departments reviewing artwork (regulatory, legal, marketing, and design teams), watertight version control is essential to avoid the simple error of using a non-approved version.
• Human error: Given the complexity of packaging artwork, manual proofreading is time-consuming and subject to human error. Easily overlooked mistakes (such as typos in dosage instructions, ingredient lists, or warnings) can risk patient health. Even minor inconsistencies in spacing, font size, or placement of information (e.g., when crucial information appears where paper is folded and therefore not clear) can jeopardize compliance if it impacts clarity and readability.
• Non-alignment with regulatory updates: Changing regulatory requirements require version review and updates where necessary. Regulations must be clearly understood, and changes to regulations should be highlighted and distributed via SOPs to those who need to know.
• Efficient approval processes: The workflow for approvals must not only be rock solid, but it must also be efficient in terms of the actual amount of time spent on approvals and turnarounds. The right people and skills must be in place for approval rounds.
Drug integrity
Security features are designed to create accountability and transparency in the supply chain, prevent tampering and adulteration, and to counter drug counterfeiting. The Drug Supply Chain Security Act (DSCSA) mandates serialization, with a barcode containing a global trade item number (GTIN), serial number, expiration date and lot/batch number. An illegible barcode is a serious violation.
Common Compliance Pitfalls
Following on from these challenges, some of the common pitfalls are:
• Mislabeling issues
Inaccurate or incomplete information, such as missing or incorrect dosage instructions, incorrect drug names, or incomplete warnings can lead to an FDA warning letter or recall.
• Failure to meet FDA formatting standards
The FDA specifies requirements for font size, color contrast, and placement of critical information. Failure to meet requirements for these design elements can make packaging non-compliant.
• False claims or misleading Information
Packaging must not contain false or misleading claims about the drug’s effectiveness or safety. Nor can it be promotional in nature.
• Lack of differentiation in smart packaging
Mandatory and supplementary smart packaging information available online – e.g., patient package inserts as opposed to promotional material – must be clearly differentiated. For example, a company would be non-compliant if it presented the material together on the same website page. Furthermore, these have different workflows, with different approval processes, people and skills involved. For more, see our article on best practices for promotional review. [9]
• PDF document format issues
PDF conversion, reading order, or hidden text in the artwork file are some common artwork file issues. Ensuring you have live text (i.e., not rasterized or vectorized) means text-to-speech applications can read the document. This is crucial in the age of e-labeling. We discuss hidden risks in artwork in an article here. [10]
Global Markets
Diverging regulatory requirements: The pharmaceutical industry is a global industry. Despite all efforts to harmonize regulations, differences are significant.
Language and translation: Packaging artwork must be translated accurately into multiple languages. Efficient workflows are needed to manage multiple language turnarounds in subsidiaries or with external providers.
Best Practices for Ensuring Compliance
1. Leveraging Technology
Artwork management systems simplify workflows. Human error can be avoided through automated proofreading, which can compare a document in seconds against an approved original document. Deviations in downstream documents become apparent immediately. Make sure your proofreading software can be integrated into your artwork management system, regulatory information management system and/or other information management systems.
Furthermore, document comparison software can be used to compare versions of regulatory and guidance documents for changes. You can immediately see what has changed.
2. Collaboration across teams
Multiple teams are involved in packaging artwork, including regulatory affairs, marketing, legal, quality assurance, regulatory operations and supply chain management. This demands clear assignment of roles and goals demands, and well-documented SOPs across subsidiaries, markets and languages. Technologies must be in place that promote collaboration.
For example, using TVT and its modules TVT Artwork and TVT Barcode (for decoding, grading and barcode readability), you can compare your packaging artwork in any language in a preliminary check against an approved document in that language before you forward it to experts in local subsidiaries. This saves time and ensures first-time accuracy.
The FDA is closely engaged with the industry, and you should also be taking a collaborative and proactive approach by engaging with the agency to clarify any open questions about your packaging artwork from the start.
3. Quality assurance with TVT
It is important to have a risk management strategy in place. This means performing ongoing risk assessments (especially, to account for regulatory changes) that identify where the risk of non-compliance is highest and to find any possible pain points in the workflow.
Automating your packaging artwork workflow is crucial to quality assurance. TVT allows you to verify text easily in the artwork file, perform pixel-to-pixel comparison of images and other graphical elements, detect variations such as in color, ensure text and the document layout match the approved version, and more. Furthermore, TVT documents all workflow steps in the verification process, providing transparency in the collaborative process and greater accountability.
Are you leveraging technologies? Have you reached optimal efficiency in the workflow? Are your people working together as a collaborate unit, or can collaboration be improved? Do you have best practices and workable SOPs in place? These are just some of the questions you need to ask to ensure compliance.
1. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/instructions-use-patient-labeling-human-prescription-drug-and-biological-products-content-and-format
2. https://www.fda.gov/files/drugs/published/Labeling-for-Human-Prescription-Drug-and-Biological-Products—Implementing-the-PLR-Content-and-Format-Requirements.pdf
3. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211
4. https://www.fda.gov/drugs/drug-supply-chain-integrity/drug-supply-chain-security-act-dscsa
5. https://www.fda.gov/media/128163/download
6. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-202/section-202.1
7. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/labeling-human-prescription-drug-and-biological-products-implementing-plr-content-and-format
8. https://www.schlafenderhase.com/shblog/best-practices-for-labeling-readability
