eLeaflets and GMP validation

The Good Manufacturing Practice (GMP) is a system for ensuring that products are consistently produced and controlled according to quality standards. GMP applies specifically to manufacturing of food, drugs, cosmetics and medical devices.

What is GMP

It is a comprehensive manufacturing system that ensures product consistency and quality by addressing 5 key components:

• products
• people
• processes
• procedures
• premises.

GMP regulations address issues including record keeping, personnel qualifications, sanitation, cleanliness, equipment verification, process validation, and complaint handling while GMP looks specifically at manufacturing most of the requirements apply also to digital solutions (like the eLeaflet) which is seen as a production line component.

Most GMP requirements are very general and open-ended, allowing each manufacturer to decide individually how to best implement the necessary controls. This provides much flexibility, but also requires that the manufacturer interpret the requirements in a manner which makes sense for each individual business.

Who certifies GMP?

Regulatory authorities or national and international supervisory bodies usually certify a manufacturer according to GMP, so for example the Food and Drug Administration (FDA) in the US or EMA in the EU would formalise GMP requirements and perform GMP validation to help companies in all industries ensure they consistently manufacture quality products.

A GMP certificate is issued on the basis of a completed GMP inspection of a manufacturer operating in accordance with the GMP guidelines.

GMP in the digital world: standards

As the industry advances, the need to align these traditional practices with modern technologies has grown exponentially. The digital transformation of GMP is not just an upgrade; it’s a revolutionary shift that offers significant benefits while presenting new challenges.

Data integrity, digital quality management systems, predictive quality control, and streamlined regulatory submissions are among the significant advantages digitalisation offers.

Data integrity is the foundation of quality compliance in GMP and ensures the information collected and stored is accurate, complete, and reliable. In the past, manual data entry processes increased the risk of transcription errors, incomplete records, and mismanagement of critical information. With digital systems, data collection and analysis can be automated, reducing human intervention and increasing real-time accuracy.

Digitalisation has enhanced the data integrity process. The US Food and Drug Administration (FDA) defines data integrity as complete, consistent, and accurate data. It provides the framework that “data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate (ALCOA).” Achieving this goal requires organisations to follow the key principles of data integrity to retrieve accurate and beneficial insights.

Electronic document management systems (EDMS) securely maintain records and help ensure compliance with regulatory standards. Technologies like blockchain and advanced analytics can improve data traceability and transparency throughout the pharmaceutical supply chain. Other examples of data integrity are seen in real-time testing results, stability data generation, and consistent backup and recovery plans.

When looking specifically at digital records and digital solutions 2 main regulations apply:

• Code of Federal Regulations 21 CFR part 11 for FDA (FDA 21 CFR part 11) and
• GMP Annex 11 for the EU (EMA GMP Annex 11).

FDA 21 CFR part 11 Electronic Records and Electronic Signatures

Requirements and Assessment

The purpose of the CFR21 Part 11 regulation, drawn up by the FDA (Food & Drug Administration), is to obtain the legal equivalence of electronic documents (digital records and electronic signature) compared to traditional paper ones. It is due to the increasingly frequent use of automation in process management in systems that must be subjected to approval and review of the federal FDA body.

So that the automation and control system created complies with the regulations CFR21 Part 11, it is necessary to ensure that the recorded data is always traceable to the responsible operator (Electronic Signature), furthermore precautions need to be taken to make falsification or tampering with the recorded data impossible electronically, they must also allow for easy identification in case of inappropriate use, whether intentional or accidental, of electronic equipment that generates electronic records.

Industries must mandate equipment that has the necessary protection mechanisms against accidental or malicious modification of data in electronic format.

GMP validation, what it is and who does what

What is GMP validation?

Good Manufacturing Practices (GMP) validation is a systematic approach that involves establishing documented evidence through a series of processes to confirm that a particular manufacturing process will consistently produce products that meet predefined quality standards.

What is the difference between verification and validation in GMP?

At a glance, the definition of validation looks very similar to the definition for verification. However, process validation measures consistency of the process against established acceptance criteria, and verification is the process to verify the compliance of the test results against established specification. So for example myHealthbox would perform a GMP verification (either internally or through an external supplier) to measure consistency of its processes against established (generic) acceptance criteria but it would fall upon the product manufacturer to perform a GMP validation to measure compliance against its own specifications.

To facilitate this process myHealthbox provides to all its customers a copy of its internal GMP verification document (the "GMP Compliance Report") so that prospecting companies can quickly incorporate this into their own QA system or identify any requirements gaps.

The myHealthbox GMP Compliance Report

Understanding of Goals and Objectives

The 21 CFR part 11 regulations set forth the criteria under which "... electronic records ... are considered trustworthy, reliable, and generally equivalent to paper records".

As for the purpose of EU Annex 11 it is to establish clear guidelines for using computerised systems in GMP-regulated activities, ensuring the reliability and security of electronic systems. The GMP Annex 11 guideline outlines requirements for implementing and validating computerised systems to ensure data integrity, accuracy, and security in GMP-related activities. EU Annex 11, while being an important document for the pharmaceutical and Life Science industries, is not a legal requirement. It is a guideline rather than a legally binding regulation.

FDA 21 CFR part 11 and EMA GMP Annex 11 both represent a guidance system for electronic records and electronic signatures in the pharmaceutical industry.

While 21 CFR part 11 is only applicable for electronic records, EU GMP Annex 11 is not limited to electronic documents. The EU system applies to software, hardware, risk management and personnel.

myHealthbox has carried out a GMP assessment of its platforms and infrastructure in response to the requirements set by the 21 CFR part 11 (FDA, US) and GMP Annex 11 (EMA, EU) directives.

The purpose of this assessment is to investigate current compliance and risks associated with: accuracy, reliability, integrity, availability, authenticity in creating, managing and distributing electronic records (eLeaflets) via the myHealthbox and eLeaflet platforms.

Limitations

"Part 11 of CFR 21 applies to records in electronic form that are created, modified, maintained, archived, retrieved, or transmitted under any records requirements set forth in Agency regulations.", as such, unless the FDA connector is used as a way to transmit the information automatically from myHealthbox to the FDA, some or all of these requirements may not apply and should be used as a guidance only.

GMP Annex 11 applies to all companies operating within the European Union in the manufacture of medical products with GMP-regulated activities, including pharmaceutical, contract manufacturing organisations (CMO), and others.

21 CFR Part 11 is a regulation and requires mandatory compliance when utilising electronic records and signatures. It carries legal weight and enforceability, meaning companies operating under FDA regulations must comply with the 21 CFR Part 11 requirements. On the contrary, EU Annex 11 is a guideline that offers recommendations and guidance for interpreting the GMP principles. It is not legally binding, meaning companies operating within the European Union market are not obligated to have compliance.

The eLeaflet, as a product, in itself is not subject to FDA or GAMP validation, but it is always the project created (and the correlated processes) in its context, that is subject to potential validation.