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Instem responds to the latest Part 11 guideline from the FDA

February 2003

21 CFR Part 11 (the Electronic Records; Electronic Signatures Rule from the FDA) was always intended to be ‘enabling’ legislation to allow the use of technology that was not foreseen when the ‘Good Practice’ rules (GMP, GLP and GCP) were drafted. Part 11 was published in March 1997 and became effective August 20th 1997. The short time between the publishing of the rule and it being effective was treated with consternation by an industry already burdened with Y2K issues.

A copy of the rule is available at www.fda.gov/ora/compliance_ref/part11

Although the rule was initially requested by industry for manufacturing the FDA reasoned that the rule should cover ‘any (electronic) records requirements set forth in agency regulations’. However, the scope of the rule adds the rider that the rule should be applied to all data submitted to the FDA ‘even if such records are not specifically identified in agency regulations’. This caused even more consternation, as it appeared that the rule should be applied to most computerised systems within a Pharmaceutical Company.

Inevitably industry required clarification of the scope of the rule and how some of the detail in the rule would be interpreted (particularly by inspectors). In attempting to assist in this clarification the FDA produced a series of guidelines covering the following:

  •  Validation
  •  Glossary of Terms
  •  Time Stamps
  •  Maintenance of Electronic Records
  •  Electronic Copies of Electronic Records

My personal view is that these guidelines were an honest attempt by the FDA to clarify the requirement. Each page of each guideline is headed ‘(Draft) Guidance for Industry – Not for Implementation’. Nevertheless, because the FDA issued the guidance it was often treated as a regulatory requirement.

Two years ago the FDA announced a new initiative to ‘modernise the agency’s regulation of pharmaceutical manufacturing and product quality’. In August 2002, FDA announced as part of this initiative that they would adopt a risk based approach to the cGMPs and outlined this in a concept paper ‘Pharmaceutical cGMPs for the 21st Century: A Risk-based Approach’. www.fda.gov/oc/guidance/gmp.html

Recently, on February 20th, the FDA issued a Press Release stating that the first stage of this modernisation had been completed. www.fda.gov/bbs/topics/NEWS/2003/NEW00872.html

The press release confirmed that the FDA would focus its attention and resources ‘on the areas of greatest risk, with the goal of encouraging innovation that maximises public health protection and promotion’.

The Press Release highlighted elements of the initiative that have been completed, including the following:

  • ‘Clarifying the scope of FDA’s electronic submission and record keeping requirements and providing for enforcement discretion in certain areas while FDA considers whether to revise the Part 11 regulations to facilitate innovation for modern manufacturing, electronic record keeping and regulatory submission.’
  • ‘Clarifying the language used to communicate deficiencies observed during cGMP inspections to better describe the purpose and effect of the investigator’s observations issued at the conclusion of an FDA inspection.’
  • ‘Focusing FDA resources on inspections that are likely to achieve the greatest public health impact (e.g. sterile drug manufacturing).’

For the remainder of this article I will concentrate on the first bullet point since on February 20th the FDA also released a new Guidance document entitled ‘Guidance for Industry: Part 11, Electronic Records; Electronic Signatures – Scope and Application’. This new guideline clarifies where Part 11 should be used but, more importantly, gives an insight into which systems, and which aspects of a system, the FDA are more likely to be concerned with during an inspection. All other Part 11 guidelines have been withdrawn.

The new guideline is available at www.fda.gov/cder/guidance/5505dft.doc

Like all previous guidance documents, this is a draft – with a 60-day comment period. Each page is headed with the text ‘Contains Nonbinding Recommendations’ and the guideline is structured along the lines of a discussion document.

The document itself is very concise – and although it is tempting to summarise it there is a danger that in doing so one only selects those aspects that would appear to be significant changes of emphasis. The guideline does, for example, state that it is the intention of the FDA to ‘interpret the scope of Part 11 narrowly’. There is also recognition that in some cases hybrid systems should be allowed (where electronic records are printed and the paper version signed). There is even allowance for the fact that systems implemented prior to August 1997 may not be required to comply with Part 11 to the same level as systems implemented after that date. Unfortunately, this could lead to the assessment that we can forget about Part 11 when that is not the case. The FDA have sensibly re-positioned the guidance to reflect what they believe is important. And central to this is the concept of RISK assessment – and focusing ones energy and resources on areas of highest risk.

The new guideline clarifies the definition of a Part 11 record and in doing so removes much of the ambiguity of the phrase ‘even if such records are not required by agency regulations’ cited at the start of this article. The guideline also gives guidance on validation, audit trails, legacy systems, copies of records and record maintenance.

The guideline makes it abundantly clear that it is the predicate rules (the GxPs) that we have to comply with. Part 11 helps us to clarify what needs to be done if we wish to use electronic records and/or electronic signatures – just as it always did. The bottom line, which applies to all systems - even those in place prior to August 1997, is that ‘all systems must comply with all applicable predicate rule requirements and should be fit for their intended use’.

Alun Nelms
Part 11 Ambassador

Postscript: BARQA intend to organise a workshop on ‘Part 11 Compliance: Assessing RISK in GxP systems’ within the next few months.

Other useful web-links:
a) Questions and Answers on the RISK based approach for cGMP www.fda.gov/cder/gmp/gmp_q&a.htm
b) FDA Press Release; August 21st 2002: www.fda.gov/bbs/topics/NEWS/2002/NEW00829.html
c) Risk based approach to 21 CFR Part 11 (prepared by ISPE) www.ispe.org/02pdf/Pt11WhitePaper.pdf

About Instem

Instem is a world-leading information solutions provider for the Life Sciences - accelerating drug and chemical development by increasing client productivity and enhancing the processes that lead to safer, more effective products.

Established in 1969, Instem has offices in the United States and Europe with its solutions supported in thirteen countries. Instem serves large multi-national corporations and smaller organizations in overcoming the challenges of managing information and provides solutions that help them further their missions while creating a competitive advantage. For more information on Instem and its solutions, please visit www.instem-lss.com or contact them by email at info@instem-lss.com.

Press Contact:

Gary E. Mitchell, VP Global Marketing, Instem US HQ
Tel: (610) 941-0990
Email: gary.mitchell@instem-lss.com

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