3. Key GxPs in Medicine

Good Documentation Practices (GDocP) are an essential of GxP compliance. Good documentation constitutes an important part of the pharmaceutical quality system and is key to operating according to GMP requirements. GDocP should be implemented to define, document, and log every critical action in the development, manufacture, and distribution of a medicine or medical device. It should assure data integrity as a key requirement of GxP, through the accuracy, completeness, consistency and reliability of the records and data throughout the data life cycle. These principles require that documentation is attributable, legible, contemporaneously recorded, original and accurate (referred to as ALCOA). This is expanded to ‘ALCOA-plus’ (or ALCOA+) by adding that documentation should be complete, consistent, enduring and available. These characteristics apply equally to both, paper and electronic records.

In essence, ALCOA defines the fundamentals for ensuring data integrity and critical elements of Good Documentation Practice as shown in the following detailed description of the ALCOA+ principles taken from the Pharmaceutical Inspection Co-Operation Scheme (PIC/S) Guidance ‘Good Practices for Data Management and Integrity in Regulated GmP/GdP Environments’, PI 041-1, (July 2021), Section 7.5: Basic data integrity principles applicable to both paper and electronic systems:

ALCOA(+) principles

A number of attributes are considered of universal importance to data. These include that the data are:

Attributable
It should be possible to identify the individual or computerised system that performed a recorded task and when the task was performed. This also applies to any changes made to records, such as corrections, deletions, and changes where it is important to know who made a change, when, and why.  

Legible
All records should be legible – the information should be readable and unambiguous in order for it to be understandable and of use. This applies to all information that would be required to be considered Complete, including all original records or entries. Where the ‘dynamic’ nature of electronic data (the ability to search, query, trend, etc.) is important to the content and meaning of the record, the ability to interact with the data using a suitable application is important to the ‘availability’ of the record.

Contemporaneous
The evidence of actions, events or decisions should be recorded as they take place. This documentation should serve as an accurate attestation of what was done, or what was decided and why, i.e., what influenced the decision at that time.

Original
The original record can be described as the first-capture of information, whether recorded on paper (static) or electronically (usually dynamic, depending on the complexity of the system). Information that is originally captured in a dynamic state should remain available in that state.

Accurate
Records need to be a truthful representation of facts to be accurate. Ensuring records are accurate is achieved through many elements of a robust Pharmaceutical Quality System. This can be comprised of:

• equipment related factors such as qualification, calibration, maintenance and computer validation.
• policies and procedures to control actions and behaviours, including data review procedures to verify adherence to procedural requirements
• deviation management including root cause analysis, impact assessments and CAPA
• trained and qualified personnel who understand the importance of following established procedures and documenting their actions and decisions.

Together, these elements aim to ensure the accuracy of information, including scientific data that is used to make critical decisions about the quality of products.

Complete
All information that would be critical to recreating an event is important when trying to understand the event. It is important that information is not lost or deleted. The level of detail required for an information set to be considered complete would depend on the criticality of the information. A complete record of data generated electronically includes relevant metadata (see section 9).

Consistent
Information should be created, processed, and stored in a logical manner that has a defined consistency. This includes policies or procedures that help control or standardize data (e.g. chronological sequencing, date formats, units of measurement, approaches to rounding, significant digits, etc.).

Enduring
Records should be kept in a manner such that they exist for the entire period during which they might be needed. This means they need to remain intact and accessible as an indelible/durable record throughout the record retention period.

Available
Records should be available for review at any time during the required retention period, accessible in a readable format to all applicable personnel who are responsible for their review whether for routine release decisions, investigations, trending, annual reports, audits or inspections.

If these elements are appropriately applied to all applicable areas of GMP and GDP related activities, along with other supporting elements of a Pharmaceutical Quality System, the reliability of the information used to make critical decisions regarding medicinal products should be adequately assured.

ALCOA is also the system used by WHO, EMA, FDA, and others and incorporated in guidelines (see below).

While some GDocP standards are codified by authorities, others are not but are considered as part of cGMP (with emphasis on the "c", or "current"). Some authorities release or adopt guidelines. While not law, (regulatory) authorities will inspect against these guidelines in addition to the legal requirements. The application of GDocP is also expanding to the cosmetic industry, excipient and ingredient manufacturers.  

The EC details documentation requirements in the context of GMP in the guideline ‘EudraLex - Volume 4 - GMP - Chapter 4: Documentation’ which contains the following items:

• Required GMP Documentation,
• Generation and Control of Documentation,
• Good Documentation Practices,
• Retention of Documents,
• Specifications,
• Manufacturing Formula and Processing Instructions,
• Procedures and records

Legal basis:

Directive 2001/83/EC Article 47f

Guideline examples:

European Commission guideline ‘EudraLex - Volume 4 - GMP - Chapter 4: Documentation’ which contains the following items

WHO Technical Report Series No. 996, 2016. Available at: WHO_TRS_996_annex05.pdf (rx-360.org)

EMA draft Guideline on computerised systems and electronic data in clinical trials (June 2021)

FDA Guidance for Industry Data Integrity and Compliance with Drug CGMP Questions and Answers (2018)

Pharmaceutical Inspection Co-Operation Scheme (PIC/S) guidance PI 041-1 (July 2021).
Chapter 7 cf. of that guideline specifically concerns the Good document management practices (GdocPs) that can be summarised by ALCOA+.