An Updated USP <1029> With Added Data Integrity?

A proposed update to United States Pharmacopoeia (USP) <1029> was published in July 2025 for industry comment. What’s changed and are the changes significant?

United States Pharmacopoeia (USP) general chapters have been a good source for “Focus on Quality” and our sister publication LCGC’s “Questions of Quality” columns. For example, USP <1058> on analytical instrument qualification (AIQ) (1-5), USP <621> on chromatography (6), and USP <1029> draft Good Documentation Guideline (7). In July, a draft update of USP <1029> was published for comment to USP by early October 2025 (8). Although informational, it offers good guidance to ensure good documentation practice (GDocP) and data integrity (DI) for pharmaceutical good manufacturing practice (GMP) regulated laboratories.

In this article, we will discuss the changes of the updated version compared to the current one and also the applicable GDocP sources listed below:

• EU/PIC/SGMP Chapter 4 Documentation (9) Principle: There are two primary types of documents: instructions that when executed generate records and reports Clauses 4.7 – 4.9 on GDocP Clauses 4.10–4.12 on document’s retention. The chapter has a proposed update issued in July 2025 that will be discussed briefly at the end of this column (10).
• WHO TRS 996 Annex 5 (11) Appendix 1: Expectations and Examples of Special Risk Management considerations for the Implementation of ALCOA Principles in Paper-Based And Electronic Systems
• WHO TRS 1033 Annex 4 (12); Guideline on Data integrity
• PIC/S PI-041 Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments (13) Section 8: Specific Data Integrity Considerations for Paper-based Systems Section 9: Specific Data Integrity Considerations for Computerised Systems

The outline of the update is shown in Figure 1. Sections that are similar but not necessarily identical with the current version are shown in green, and additions in the draft version are presented in yellow. The title has been changed and expanded to include DI. It provides the main reason for differences in the content of the draft version against the current one.

Our comments in this column follow the main headings of the USP <1029> update.

Purpose and Scope

The purpose presents documentation as both paper and electronic forms. Later in this document, the DI section uses the term of media to describe paper, electronic, or hybrid. This addition is consistent with other guidelines (9,11).

The scope has been expanded to include DI and GDocP and data governance (DG), as USP has no general chapter covering these topics. There are fewer details on DG and the draft 1029 simply provides a definition. Although the core context of DG definition stays consistent with the regulations and regulatory guidance (13,14), our suggestion is to consider all phases of data lifecycle and include generation and destruction steps into the definition. A further addition could be Data governance should ensure the application of ALCOA+ principles from Section 4.4 of WHO TRS 1033 Annex 4 (12).

The introductory briefing to the draft of USP <1029> states that data governance will be the subject of another general chapter in the future (8);this is good, especially given the emphasis on DG in the recent update of EU/ PIC/S GMP Chapter 4 (10).

Good Documentation Practice, Data Integrity, and Data Governance

As shown in Figure 1, this is a new section, and it highlights key DI elements and provides a unified approach to the regulatory and pharmacopoeia requirements. Examples include the provisions on the electronic record and the requirements on instrument and system qualification:

...Electronic records must meet the requirements of the Code of Federal Regulations in title 21 (21 CFR) part 11 and applicable predicate rules.

...All general chapters and monographs require the use of qualified instruments and systems to produce data, which is processed and evaluated to produce reportable results.

As illustrated in Figure 1 of USP <1029>, the draft update embeds the elements of data lifecycle management into DG, DI and GDocP as follows:

• Roles, responsibilities, policies, and procedures defined in the PQS
  This reflects a number of DG measures and agrees with PIC/S PI-041 5.2.1 states “Data governance systems should be integral to the Pharmaceutical Quality System [PQS]...” (13).
• Record data, metadata, and results in accordance with policies and procedures and review; retain and ar chive records ensuring tractability
  It highlights DG organizational controls in terms of understanding the “how” perspective of data management processes over the life cycle similar to PIC/S PI-041 section 5.2.3 (13). The section on Best Practice Principles provides further details on these controlling items.
• Ensure GDocP and DI policies and procedures comply with regulations. It is similar to PIC/S PI-041 definitions and WHO TRS 1033 Annex 4 10.1 and demonstrates how GDocP correlates highly with DI assurance:
  • ...Assuring data integrity requires appropriate quality and risk management systems, including adherence to sound scientific principles and good documentation practices... (13).
  • Those measures that collectively and individually ensure documentation, whether paper or electronic, meet data management and integrity principles, such as ALCOA+ (13).
  • Good documentation practices should be implemented and enforced to ensure compliance with ALCOA+ principles (12).

The review and revise phase implies taking a risk-based approach over all the process activities, which is in sync with other regulatory guideline and guidance documents (12,13).

Best Practice Principles for Good Documentation

Apart from the addition of Best Practice in the heading there are several changes for the better in this section. The introduction is the same in the two versions:

However, a potential omission is explicit mention of the drug development phase which uses pharmacopoeial analyses. WHO TRS 996 Annex 5 clause 1.1 (11) considers the development phase based on data influencing regulatory decisions which is also reflected in FDA’s Compliance Policy Guide (CPG) 7346.832 (15,16).

All the bullet points about controlling measures have been updated:

• Secure controls are necessary for ensuring data integrity throughout the data lifecycle. Our suggestion is to highlight the importance of controlling master documents in this section, as suggested by PIC/S PI-041 Section 8.4 (13).
• A simple statement: There is only one GMP record (8). Implicit is that a GMP record will consist of the reportable result together with all the underlying data and metadata which must comply with the GMP requirement for complete data in 21 CFR 211.194(a) (17). This will include any system suitability tests as well as any deviations and resolution encountered during analysis
• Records must have a defined owner. What is omitted is the impact of data lifecycle on ownership. Usually there is a hand-over from the laboratory to a records management group or archivist at some time after batch release for long term storage. Archiving paper records is easily understood. For a better understanding of electronic archiving, read Section 8 of OECD GLP No. 15 (18).
• Records need a retention schedule or specific retention schedule. Companies should also check for any pending or ongoing legal action before destroying records.
• Records, especially electronic ones, may require maintenance.For example, an upgrade of the application or migration to a new format throughout the retention period. There may be a need to retain the software to re-open data. Many laboratory records are dynamic and must remain in this state during retention (13,14,19) and be available in case of deviation, complaint, audit or inspection.

A records management inventory is required for all documents to assure traceability that lists the record owners, retention period and all record type(s). In addition, inventory should be the location(s) of the records, see Section 8.4.1 of PIC/S PI-041 (13).

Data Integrity and ALCOA++ Principles

The major and very welcome change in USP <1029> is the inclusion of a large section on ALCOA++ principles, which reiterates the underlying connection between a well-designed PQS and DI principles.

The new version has a completely new section covering ALCOA, ALCOA+, and traceability of the ALCOA++principles. ALCOA and its variations were discussed in this column previously (20), with the title Is Traceability (the 10^th criterion) the Glue for ALCOA,ALCOA+ ,or ALCOA++? A figure in the draft USP <1029> shows nine ALCOA+ criteria surrounded by traceability over the life cycle as an excellent way of demonstrating how traceability is the glue for data integrity (20). It is reproduced in Figure 2 of this article.

The best description of ALCOA principles can be found in Appendix 1 of the 2016 WHO Guidance on Good Data and Record Management Practices (11), which was unfortunately replaced by an inferior DI guide in 2021 (12).

In this section, we are not providing a line-by-line discussion of each principle. We discuss key items only:

• Attributable: States that work can be performed by a computerized system as well as a human which is consistent with DI guidance documents (11,13,14) and GAMP 5 SE (21). However, if you have set up a sequence to run overnight and go home, do you want work to be attributed to you when you are a couch potato watching TV? Systems need to attribute work to the user who started the sequence but to the system for subsequent automated actions. The phase when the task was performed (8) must be translated to add the date and, when necessary, time to the record (11). It is imperative to consider unique identification of a person or a computer system. For example, for multi-site systems, location should be identified (12). Providing a unique identifier and version control to GMP records is discussed under Data Collection and Recording. This section also refers to some other attribution factors such as use of signature and initials for each responsible person, and explains the need for entering change reasons.
• Legible: The section Data Collection and Recording puts emphasis on legibility within change control and repeats:

Any change to existing entries should be made in a way that does not obscure the original entry...

• Original: This criteria simply considers the first capture information however as WHO TRS 1033 Annex 4 example 9 and MHRA definition of raw data indicate, the subsequent data also required to fully reconstruct the conduct of the GxP activity (12,14).The role of true copy is also relevant to this requirement and discussed in Data Collection and Recording. Further details on certified copy can be found in other regulatory guidance (11,12,22).
• Accurate: Key features are:
  • Use of qualified instruments and validated systems
  • Rounding rules (this can also be classified under consistency).
• Complete: Second person review is a crucial requirement to ensure that data are complete. Although it is missing in ALCOA line, the section on Data Collection and Recording gives the required description.
• Consistent: The draft mentions that the number of significant figures must be maintained during the metrological, calculation and reporting process. Rounding of the reportable value to the same number of significant figures as the specification or acceptance criteria is performed at the final step. Consistent also implies following all operational standards of practice (SOPs) and procedures as written.
• Traceable: As shown in Figure 2, traceability is the glue that brings all other ALCOA criteria together and enables data to be traceable throughout the life cycle. Any change to data or metadata must be explained and not obscure the original; all recorded in the audit trail or on paper depending on the record medium. Time sources must be traceable to a trusted source. Metrological standards used for instrument or system qualification need to be traceable to international standards wherever possible and preparation of reference standards should follow ISO 17034: 2016 (23). Inclusion of traceability is also consistent with the EMA clinical guidance for computerized systems (24).

Good Documentation Practice, Data Integrity & Data Governance

Continual Versus Continuous Improvement?

It is important to remember that regulated laboratories require control and, in this section, there are two mentions of continuous improvement plus the legend of Figure 1 which is incorrect. Both ICH Q10 and EU GMP Chapter 1 (25,26) refer to continual improvement which is a discontinuous process allowing for change control.

Interestingly, the section on DI refers to continual improvement, so it may be an error in the final editing of the draft before publication.

Protocols and Reports

This section has expanded to include protocols and reports for process equipment qualification, analytical instrument and system qualification and computerized system validation and technology transfer. Inclusion of process equipment qualification is important for traceability especially in failure investigation of out of specification (OOS) results (27).

Equipment, Instruments and Systems Documentation

There is an issue with wording: apparatus, instrument, and system are used in USP <1058> (5,28) and we have equipment, instruments and systems in USP <1029> (8). We need consistency. Is there a collective noun for this stuff? Kit!

A major problem with this section is with logbooks: equipment use logs and maintenance records are listed in two separate bullet points in both the current and update of USP <1029> (8,29).

This is misleading, as it gives the impression that instrument use and any associated maintenance records are separate but they must be considered in combination. We need to understand why instrument use and maintenance must be treated as one item. At this point, you must follow Cahn’s Axiom: when all else fails, read the SOP, manual or in this case the applicable regulation. 21 CFR 211.182 sets out the requirements for an equipment cleaning and use log (17).

• A written record of major equipment cleaning, maintenance (except routine maintenance such as lubrication and adjustments), and use shall be included in individual equipment logs that show the date, time, product, and lot number of each batch processed..
• The persons performing and double-checking the cleaning and maintenance...shall date and sign or initial the log indicating that the work was performed.
• Entries in the log shall be in chronological order.

Therefore, ALL maintenance and use entries must be included in a single instrument logbook, in chronological order. DO NOT separate maintenance from use otherwise you will not be compliant. FDA do cite organizations for logbook failures: see the annual listing of 483 observations available in the web site (30). Is it too much to expect USP and FDA to be aligned?

Note, also, the requirement for a second person to review logbook entries. This is the only GXP regulation to require this. It is sound science and a good regulatory requirement. EU, PIC/S GMP, OECD and FDA (Food and Drug Administration) GLP regulations do not mandate a second person review (9,31,32), but they should. The humble instrument logbook has been discussed earlier in this column (33). Separating maintenance from use does not meet the ALCOA++ consistent criterion. Burgess and McDowall have written an article entitled “Do Pharmacopoeias Inadvertently Encourage Data Integrity Violations?” for further reading (34).

Training Documentation

The new version has the addition of successful training criteria, which is a most welcome addition and implies the need of competence assessment or understanding before performing a task. This section should also state that training should be performed prior to any approved procedure being effective. This would be consistent with PIC/S PI-041 section 8.4 (13).

Retention of Documents

The retention section needs enhancement. According to ALCOA, A complete record of data generated electronically includes relevant metadata (29). This is consistent with 21 CFR 211.194(a) especially with the importance of metadata retention (17).

Draft EU/PIC/S GMP Chapter 4 Comparison

A week after publication of the USP <1029>, a draft update of EU GMP Chapter 4 on Documentation was issued for stakeholders’ comment (10). It is an opportune moment to compare the two:

• As the USP <1029> is an above 1000 general chapter, it is informational or strong guidance compared with Chapter 4 which is a regulation. Note that FDA can and will cite >1000 general chapters in 483 observations, which escalate them to requirements.
• Chapter 4 covers all GMP records while USP <1029> is focused on laboratory records associated with pharmacopoeial analysis. EU GMP/PIC/S Chapter 6 on Quality Control also has requirements for laboratory analysis (35).
• USP <1029> provides a succinct and easy to interpret requirements for both DI and GDocP.
• In contrast, EU GMP/ PIC/S Chapter 4 has ballooned from a Principle and 32 clauses to a Principle and 85 clauses (along with a new glossary) making it less interpretive and more prescriptive with much repetition. Bloated and repetitive are two words to add to the description. EU GMP/PIC/S Chapter 4 has a section on hybrid systems that is better included in the EU GMP PIC/S Annex 11 revised draft.

Summary

We have reviewed the proposed update to USP <1029> versus the existing version of GXP regulations and guidance. The extension to include DI and the importance of ALCOA++ criteria is good progress. What is needed is a separate general chapter on DG. There are minor criticisms and comments but the draft is an improvement on the current version and is consistent with other regulatory guidance documents. Moreover, it is easy to read and interpret, unlike the snoozefest that is the proposed update to EU PIC/S GMP Chapter 4 on documentation.

Acknowledgements

We would like to thank Markus Dathe, Bob Iser, and another individual for their constructive reviews of this column.

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