What is ALCOA+ and Why Is It Important to Validation and Data Integrity

ALCOA+ is a set of principles that ensures data integrity in the life sciences sector.

It was introduced by, and is still used by, the FDA – the US Food and Drug Administration. It has relevance in a range of areas, particularly in relation to pharmaceutical research, manufacturing, testing, and the supply chain. 

As well as being crucial for compliance reasons, ALCOA+ principles are becoming increasingly important to GMP (Good Manufacturing Practices). Their relevance is also growing as manufacturers in the life sciences sector continue to implement Smart Factory solutions and processes.

The Importance of Data Integrity 

Data has always been important in pharmaceutical manufacturing and research. However, a range of different factors means the importance of data is growing exponentially. Key to this is the move away from paper-based records to digital data collection, storage, and processing. 

Advances in technology, increasing levels of automation, the globalization of the life sciences sector, and the use of contract manufacturers mean it is also now more important than ever to ensure data integrity through the entire product lifecycle.

Other drivers for the growing importance of data include:  

• The importance of ensuring the quality and safety of medicines

• Enhanced regulatory requirements in relation to data, traceability, and audit trails 

• The evolving expectations of consumers and end users 

• The increasingly competitive nature of the pharmaceutical industry 

• The fact that almost all Industry 4.0 technologies and systems rely on deeper levels of equipment integration and a vastly increased volume of digital data transfer  

You can’t just have data, though, as data integrity is as important as the data itself. When you have data integrity, you have data you can use and rely on. That’s where ALCOA+ comes in.  

Data Integrity and GMP Records

The ALCOA principles that ensure data integrity apply to the following types of GMP records: 

• Electronically recorded – data recorded using equipment from simple machines through to complex and highly configurable computerized systems 

• Paper-based – a manual recording on paper of an observation or activity 

• Hybrid – where both paper-based and electronic records constitute the original record 

• Other – this includes photography, images, chromatography plates, and more. 

ALCOA and ALCOA+ Principles

ALCOA is an acronym for the original five principles of data integrity. Those principles are: 

• Attributable

• Legible 

• Contemporaneous 

• Original

• Accurate  

These original ALCOA principles have since been updated to ALCOA+. The original principles remain with four additions:  

• Complete 

• Consistent 

• Enduring 

• Available  

Let’s look at each of the principles in more detail. 

Attributable

To ensure collected, generated, or updated data is attributable, the following must be recorded:  

• The identity of the person, system, sensor, equipment, or device that collected, generated, or updated the data 

• The source of the data 

• The date and time  

The above applies whether the data is collected, generated, or updated automatically or manually.  

Ensuring data is attributable is not a technical issue, as all modern (and many old) systems and software applications have the above capabilities. The main challenges come with procedures and policies.  

An example is password integrity, where one password is used by multiple workers. When this occurs, data that is collected, generated, or updated is not attributable.  

Digital Implementation

• Single Sign-On (SSO)

• Biometric authentication

• 21 CFR Part 11 compliant e-signatures

Benefit

• Eliminates shared passwords

• Ensures every action is traced to a specific, verified individual

Legible 

Ensuring data is legible is about more than being able to read the data clearly, although that is important in situations where manual record-keeping takes place. Being able to make out words and figures is much less of a problem with electronic data, though. 

That said, legibility still has relevance when data is digitally created, generated, or updated, as it is essential that data can be read and understood years and even decades after it’s recorded. This point is as relevant to digitally recorded data as it is to data recorded in notebooks. 

So, it’s important to avoid using clichés and unusual phraseology as this may be difficult to decipher in the future without getting clarification from the originator of the data, a person who may no longer be available. 

Using consistent, straightforward language throughout an entire organization, regardless of locality, is the best approach. 

One final point to consider in terms of the legibility of data is that data collected, generated, or updated must be permanent. 

Digital Implementation

• Standardized data fields

• High-resolution audit trails

• Permanent file formats

Benefit

• No more bad handwriting or faded paper

• Records remain readable for decades

Contemporaneous

It’s essential that individuals or systems record data whenever an activity or action takes place. With electronic data, timestamping is usually normal practice, although there are some points that should be considered. This includes ensuring data operations are not held in a queue that could delay timestamping while also ensuring system clocks are accurate and time zones are recorded. 

In general, though, contemporaneous data recording is another point that has more relevance to manual record-keeping. The main aim is to avoid the practice of creating or updating data at some point in the future. When data is recorded after an event or action, mistakes can happen, i.e., elements can be forgotten, parts can be left out, and information can be recorded inaccurately. 

Digital Implementation

• Automatic, real-time timestamping synced to a central Network Time Protocol server

Benefit

• Prevents backdating and memory errors

• Records are created when events happen

Original

Records should be original rather than copies or transcriptions. Again, this applies mostly to manual record-keeping. For example, you should not write information on a scrap of paper with the intention of completing the main record later, as this can result in errors. 

Instead, the original recording of the data should be the main record, whether that record is on paper or on a digital system. With digitally recorded data, it is also important there are technical and procedural processes in place to ensure an original recording of data cannot be changed. 

Any analysis, reports, or calculations based on data collected, generated, or updated should be traceable back to the original source. 

Furthermore, copies of an original record should be formally verified as being true copies, and they should be distinguishable from the original. The original version of the data should also be preserved, even when copies exist. 

Digital Implementation

• Direct data capture from sensors and PLCs to the database (Primary Record) with automated backup and version control

Benefit

• Ensures the source of truth is preserved

• No manual transcriptions or risky paper processes required

Accurate 

All records should reflect the reality of what happened and should be error-free. Also, there should be no editing of the original information that results in that information being lost. 

If changes are necessary, those changes must be documented in a way that makes it possible to refer back to the original information. Nothing should be removed, blocked out, or deleted. 

When recording data electronically, the system must have built-in accuracy checks and verification controls. Measurement equipment should be regularly calibrated as part of this process. 

Digital Implementation

• Automated data validation

• Integrated instrument calibration tracking

• Removal of manual entry

Benefit

• Helps ensure data reflects the true process conditions

• Reduces human error and OOS (Out of Specification) findings

Complete

All recorded data should have an audit trail to show nothing has been deleted or lost. This doesn’t just cover the original data recording but also metadata, retest data, analysis data, etc. There should also be audit trails covering any changes made to the data. 

Digital Implementation

• Mandatory data entry fields in EBR

• Automated logging of all metadata

Benefit

• Prevents missing data points that often lead to batch rejection or audit observations

Consistent

This primarily means ensuring data is chronological, i.e., has a date and time stamp that is in the expected sequence. Changes made to an original data recording should be timestamped. 

Digital Implementation

• Standardized digital workflows

• Automated audit trails that record events chronologically

Benefit 

• Ensures every batch follows the same validated path, regardless of the operator or site location

Enduring

While durability is a factor in many of the above data integrity principles, ALCOA+ places specific emphasis on ensuring data is available long after it is recorded – decades in some situations. 

For digitally recorded data, specific steps should be taken to ensure data is enduring, including putting in place robust and tested data backup systems, as well as disaster recovery plans and uninterruptible power supplies. Cybersecurity is also an important consideration. 

Digital Implementation

• Validated cloud storage

• Long-term archiving

• Redundant data backups

Benefit 

• Protects records against physical damage, loss, or technological obsolescence

Available

Data must not only exist, but it must also be accessible. So, data storage systems should be searchable, with data properly indexed and labeled. The most efficient way of achieving this is normally by recording data electronically. 

By being available, the data must be readable at any time during the retention period. This could be for a range of purposes, including audits, reviews, and inspections. 

Digital Implementation

• Centralized data lakes / historians

• Secure remote access for auditors

Benefit 

• Significantly reduces audit preparation time by providing instant data retrieval

The Data Integrity Lifecycle

• ALCOA+ principles apply throughout the entire data lifecycle: 

• Creation – from sensors, systems, operators, etc 

• Processing – during analysis, calculations, and comparisons 

• Use – reviews, reporting, and analysis 

• Retention and retrieval – storage of data as well as retrieval for auditing and other purposes 

• Destruction – the destruction of data at the end of the retention period 

The Importance of Data Integrity in the Life Sciences Sector

Data integrity is essential to all validation processes in pharmaceutical and medical device manufacturing facilities. Understanding and following the ALCOA+ principles will help you ensure data integrity, especially when selecting data solutions and implementing data recording and documentation protocols. 

With data integrity now so intertwined with product quality, patient safety, and regulatory compliance, following the ALCOA+ principles should be a high priority for all life sciences sector manufacturers.