Ignoring the warning signs of non-compliance is no longer an option
Data shows that more than half of all FDA recalls of medical devices since Q1 2014 have been caused by packaging and/or labeling error. One of the most high profile recent examples was the Class I recall of a Peripheral Infusion System, where major mislabeling risked the incorrect use of the product by physicians and raised the potential for serious patient injury or death.
Despite this, and despite the fact that label inspection is a regulatory requirement in both the US and European markets, irrespective of the size of an organization, with clearly unambiguous global guidelines, many within the industry appear unclear on the nature of FDA regulations. A 2016 survey we undertook of medical device and pharmaceutical organizations revealed that almost two thirds of respondents are either unsure or unaware of the FDA’s regulations on the quality system requirements for label inspections.
An example of some of the regulatory compliance requirements you will need to consider for inspection are as follows:
FDA 21 CFR820.80b deals with Quality System Regulation for medical devices. It talks about the requirement for ‘incoming product’ to be inspected. In this instance, incoming product is anything that arrives from another organization and includes labeling.
FDA 21 CFR820.80b
Receiving acceptance activities. Each manufacturer shall establish and maintain procedures for acceptance of incoming product. Incoming product shall be inspected, tested, or otherwise verified as conforming to specified requirements. Acceptance or rejection shall be documented.
FDA 21 CFR820.120 is specific to device labeling. The guideline sets out a range of regulations to ensure manufacturers establish and maintain procedures to control labeling activities. These include label integrity, storage, operations and control numbers. Clause B focuses on labeling inspection:
FDA 21 CFR820.120
Labeling inspection. Labeling shall not be released for storage or use until a designated individual(s) has examined the labeling for accuracy including, where applicable, the correct unique device identifier (UDI) or universal product code (UPC), expiration date, control number, storage instructions, handling instructions, and any additional processing instructions. The release, including the date and signature of the individual(s) performing the examination, shall be documented in the DHR.
FDA 21 CFR820.30 looks at design controls, mandating manufacturers to establish and maintain procedures to control the design of the device to ensure that specified design requirements are met. Although its relevance to labeling is less explicit, the regulation requires that final labels match the content of the design history record (DHR). If the applied label deviates from master records or the DHR the product may be considered adulterated.
FDA 21 CFR211.122, subpart G, deals with packaging and labeling control. It stipulates the need for written procedures to document the receipt, identification, storage, handling, sampling, examination and testing of labeling materials. It also details the requirement to maintain a robust audit trail of labeling activities, both approved and rejected. More specifically, clause G parts 2-4 highlight the importance of 100% inspection:
FDA 21 CFR211.122g
… labeling operations shall include one of the following special control procedures:
(1) Dedication of labeling and packaging lines to each different strength of each different drug product;
(2) Use of appropriate electronic or electromechanical equipment to conduct a 100-percent examination for correct labeling during or after completion of finishing operations; or
(3) Use of visual inspection to conduct a 100-percent examination for correct labeling during or after completion of finishing operations for hand-applied labeling. Such examination shall be performed by one person and independently verified by a second person.
Finally, the EU is not immune to labeling inspection.
EU Directive 2001/83/EC, article 65, outlines how, in consultation with Member States, the Commission shall draw up and publish detailed guidance concerning a range of medical/healthcare products. These include:
• The wording of certain special warnings for certain categories of medicinal products;
• The particular information needs relating to non-prescription medicinal products;
• The legibility of particulars on the labeling and package leaflet;
• The methods for the identification and authentication of medicinal products;
• The list of excipients which must feature on the labeling of medicinal products and the way in which these excipients must be indicated.
In summary, the scope and detail of global regulations underline that the 100% inspection of labels in the production, manufacture and distribution of medical devices is a requirement not an option. To underline the point, the FDA has already begun to issue warning letters to organizations that have fallen foul of its quality system regulations. In 2014, 48 warning letters were issued relating to breaches of CFR820.80 and an additional four were issued regarding CFR820.120. These notices, quite literally, serve as a warning that companies must set in place robust mechanisms and processes to manage risk and maintain compliance.
Companies need to find a solution that removes the risk of human error, gives them end-to-end label tracking and the ability to understand that what was sent to the printer not only physically printed, but can also be proven in a single audit log.
About the author:
Phil Dray is Senior Test and Validation Engineer at PRISYM ID, ensuring regulatory compliance to FDA, MHRA, EU and GMP for the company software products supplied to the Life Sciences Industry. He also ensures that validation documents and processes are in line with current regulatory guidance, and provides onsite training for PRISYM ID’s proprietary software for the Life Sciences industry.
He provides test plans and processes to ensure software products are robust before release.