21 CFR Part 11 GMP Difficulties and Confusion?

21 CFR Part 11 GMP Difficulties and Confusion?

Further, 6 times have ceased the US Food and Drug Administration. 21 CFR Part 11 GMP regulations regarding the use of electronic records and electronic autographs came into effect. In February 2003, FDA issued new draft guidance concerning the compass and operation of Part 11. which describes how the agency intends to interpret and apply the conditions during its ongoing reappraisal of the regulations. Numerous people in the pharmaceutical assiduity have eaten this new guidance. See it as a positive development that will lead to a simplified FDA approach to Part 11 and a significant reduction in the assiduity’s compliance burden.

The root causes 21 CFR Part 11 GMPS

Numerous factors have been suggested as reasons for the contestation and confusion that have girdled 21 CFR Part 11 GMP within the pharmaceutical assiduity. These conversations have generally concentrated on FDA’s sweats. The assiduity’s arguments that the agency has failed to give timely and sufficiently specific guidance. To fill in all the details that lurk beneath the high- position principles outlined in the regulations. The root causes of the problems, still, point to both FDA and the assiduity.


Moment, pharmaceutical companies don’t question the need to duly validate product processes. It has come alternate nature for this to do in a planned, structured, controlled and precisely proved way. The assiduity readily accepts and understands the notion that you cannot test quality and integrity into a product. This understanding also extends to the conception that product quality integrity affect from following a good, scientifically challenged.


What the assiduity didn’t appreciate in the early 1990s and still struggles to accept is that the veritably same generalities apply to the quality and integrity of motorized systems.

As these attributes in the electronic environment also affect from following a planned, rational, controlled and proved process. For a variety of reasons, the assiduity has generally not successfully transferred its understanding of these process- acquainted generalities into the electronic terrain. This non-transference, combined with the poor position of being software and systems development practice, helped to produce  the assiduity’s share of the root causes of Part 11 issues.


Shifting the culture pattern



The differences in views and understanding between the assiduity and FDA regarding good practice in this area have redounded in multitudinous adverse inspectional findings and the pain and expenditure of nonsupervisory enforcement conduct. 21 CFR Part 11 GMP has been an effective motorist in this process and a leading cause in driving the onsets of a significant but grudgingly accepted culture change in the assiduity. The pharmaceutical assiduity is witnessing, but still defying, a major paradigm shift in terms of its approach to software and systems development.


Why is such a culture change necessary?

Because indeed though there are some areas of good practice, it isn’t yet bedded in the assiduity’s culture. There’s still a wide lack of understanding regarding the logical and scientific base for some of the crucial conditions and this continues to fuel companies ‘and individualities’ resistance to espousing practices that will routinely meet those conditions. The Part 11 demand for automatic, computer-generated, time- stamped inspection trails is a high illustration. Numerous people in the assiduity still view this as a fresh, gratuitous demand that’s being assessed by the controllers for purposes of easing examinations, and inhibiting and being suitable to descry fraud. This mindset is deceived, as an inspection trail is a rational, introductory element of good practice, the primary purpose of which is for the company’s benefit, not the controllers’.

The core problems

Following the allocation of Part 11, incremental guidance flowed out of FDA in both functionary (but draft) guidance documents and unofficially in multitudinous statements and opinions handed as” tribune policy “by agency officers at colorful meetings and conferences. Numerous of the assiduity’s complaints then are well- innovated. Indeed, FDA’s interpretation of the conditions did creep with time, and redounded in some illogical and gratuitous axes. The positions set forth in FDA’s draft guidance on electronic clones of electronic records give a good illustration.3 In that draft guidance, FDA sought to put fresh conditions that went far beyond the letter and original spirit of the regulations; for illustration, when FDA 21 CFR Part 11 GMP for the first time” suggested “that audited enterprises “should” convert original electronic records into another format to accommodate the agency’s specialized capabilities.


FDA’s inconsistent and sometimes over-reaching guidance clearly did contribute to the pharmaceutical assiduity’s difficulties, but it was the underpinning state of the assiduity’s practices that truly presented the core problems. Because the assiduity didn’t completely understand or cleave to introductory good software and systems development practices, companies anticipated (and, in numerous cases, demanded) FDA to be much more unequivocal, conventional, and definitive in its Part 11 guidance.

It was unreasonable and unrealistic to anticipate that FDA 21 CFR Part 11 GMP would or indeed could educate the assiduity about software and systems development, particularly since the generalities and norms weren’t new and the assiduity had much lesser specialized capabilities than the nonsupervisory authorities could apply to these issues. The more it appeared that FDA was making up the rules as it went on, the further the assiduity plodded and came entangled in its own internal debates regarding the introductory prospects and how to effectively meet them.


The typical commercial structure employed in the assiduity has also been a core problem in fueling companies’ difficulties. In general, information systems (IS) or information technology (IT) functions haven’t been approached as a core faculty in the pharmaceutical assiduity.

In utmost companies, IS/ IT departments are established and managed primarily as a service function to the rest of the business. The IS/ IT association is naturally considered as an executive or structure necessity that’s there to respond to and support the company’s more critical core business demands in exploration and development, manufacturing and marketable operations. As a result, the IS/ IT departments’ objects and pretensions have generally been riveted on and driven more by system delivery deadlines and budgets than by quality and good practice.

To add to the problem, the budgets for IS/ IT development and the use and conservation phases of systems are generally managed in separate corridor of the company. This separation of financial responsibility leads to a tendency to develop systems and pass them to the business function, which must also deal with the consequences of any development failings. With this approach, the development association is considered to have met its objects if it delivers a new system on time and under its operating budget, indeed if opinions were made to skip crucial development way (similar as integration or system testing) to meet the delivery deadline. Despite its obviously shortsighted nature, this approach isn’t uncommon, and companies frequently dodge change and conservation charges that far outshine the costs to duly develop the system in the first place.

FDA’s new draft guidance

On 20 February 2003, FDA issued a new draft guidance regarding the compass and operation of Part11.5 In this draft guidance, FDA described its “narrowed” interpretation of the regulations and explained how it intends to apply its enforcement discretion during its ongoing reappraisal of Part 11 as part of its new” wisdom and threat- grounded approach “to good manufacturing practices (GMPs) for medicinal.

The agency also withdrew all its former draft Part 11 guidance and its 1999 Compliance Policy Guide regarding the enforcement of Part11.6 In summary, the new guidance document more explicitly states what FDA has been saying for some time-that until it decides how it intends to go forward with Part 11 in the environment of the new GMP action, it isn’t going to apply a number of the Part 11 conditions per se, but will completely apply the conditions of the predicate rules.

For some of the FDA- regulated diligence, this shifted enforcement focus will presumably affect in a significantly reduced impact of Part 11 conditions on their businesses as a practical matter. This won’t probably be the case for the medicinal, medical device and biologics diligence; still, because numerous of the conditions of Part 11 are also easily needed under the being predicate rules for manufacturing, clinical, laboratory and other nonsupervisory practices.


Has the guidance helped?

There’s a question whether FDA’s most recent draft guidance will really help the pharmaceutical assiduity and at the same time palliate the agency’s enforcement burden. At the onset, FDA may be creating further issues than it’s aiming to break.

Some of the language in the draft guidance is contrary to long- standing FDA positions and some of it clearly seems to be unrealistic in light of the assiduity’s practices. For illustration, in the draft guidance, FDA suggests that some systems may not need to be validated.7 for decades; FDA 21 CFR Part 11 GMP has constantly taken the sensible scientific position that all systems should be validated, according to their intended use.

This new approach undermines that position, and potentially opens the levees. For undetermined threat- grounded opinions to not validate certain systems. In fact, some companies are formerly (and inaptly) interpreting the draft guidance as supporting their using “a justified and proved threat assessment “to avoid validating systems that easily fall within the confirmation conditions of the predicate rules.

Threat assessment


FDA’s 21 CFR Part 11 GMP suggestion for the development and use of threat assessments related to motorized systems makes sense from both a scientific and a nonsupervisory perspective. It’s also harmonious with standard engineering approaches to hazard control. The difficulty is that the agency’s abstract explanation formerly again seems to be heading for another incarnation of the” reality gap” problem.


The generalities and styles of hazard control and threat mitigation aren’t well- understood .Routinely employed for software development in the pharmaceutical assiduity. Unlike the knowledge and capabilities that have been developed in the medical device. Assiduity regarding the understanding and operation of threat, the pharmaceutical assiduity generally has much more limited experience in the homogenized operation of hazard control methodologies.


This has been reflected in a number of problematic examinations. Where internal opinions and boundaries as to what was done or should have been done (for illustration, with regard to the compass of testing) wasn’t predicated in good wisdom. Sense or grounded on a thorough understanding of the design and intended functionality of the software and system. Without the scientific and logical foundation handed by the rigorous operation of a hazard control methodology. This type of approach appears to be arbitrary and becomes veritably delicate for the audited company to defend.


FDA’s recent draft guidance raises a number of new abecedarian questions. Sets the stage for further contestation and confusion regarding 21 CFR Part 11 GMP how it’ll be interpreted and executed. Given this reality, one thing seems clear-there’s further cooperative work to be done. FDA and the pharmaceutical assiduity are going to succeed in reducing their separate compliance and enforcement burdens.

Leave a Reply

Your email address will not be published.