21 CFR Part 11 was not among the earliest of quality related regulations imposed on the drug and medical device manufacturing industries. That honor was bestowed on the compulsory retention of samples of every batch of production along with all the individual critical manufacturing records of these batches. This meant all process manufacturing equipment had to be equipped with sensors that would record each of the critical process parameters. These 21 CFR Part 11 records were mainly created by the use of chart recorders and the final chart recorder log sheet became one of the main critical records of manufacture. So your retention production records would include all these machine log sheets along with the process instructions (SOP’s) the operators worked to; and the certification records of the individual batch raw materials. All these records were required to be stored in accordance with requirements.
Most of these log sheets were issued with part numbers and individual serial numbers and were; as blank sheets, treated as, 21 CFR Part 11 controlled documents. After use they were signed off by the operator, their supervisor and usually QA, prior to being accepted as an official production record. This rendered these documents as fairly robust records of production. Illicit alterations were quite easy to spot - inks dried differently - hand writing varied enormously - access to the documents was controlled and all corrections or alterations needed a supervisors counter signature. That was the situation for many years and where someone did try to make illegal alterations it was usually quickly recognized as such.
Through the eighties and nineties the progressive introduction and use of computer controlled and computer managed equipment meant that 21 CFR Part 11 records were being produced electronically and held in volatile memories; ready for downloading into a hard copy format that would act as the requisite record. It was quickly recognize by the regulators that this record was not secure, as the data was open to adulteration all the time it was held in the volatile memory and even after it was printed out into hard copy. The robustness of the production record had been lost and the requirement for a more secure way of obtaining and storing cGMP mandated data had arrived. Therefore the record must be immediately printed out in hard copy that is designed to be as robust as the original record, or it must be retained in a protected memory that has been designed to be compliant with the requirements of 21 CFR Part 11.
So the whole intention of Part 11 is to ensure that the predicated retention records are held in a format and system that renders unauthorized editing and deletion to impossible. Further requirements mandate security of access to the records and a bibliography of amendments
Just what does 21 CFR Part 11 apply to? It has become obvious to all persons who use any IT facility that electronic data is extremely easy and simple to manipulate and or corrupt; either knowingly or unknowingly. The regulations contained within protects predicate rule information from such corruption, and gives assurance of the data integrity.
21 CFR Part11 and Protocols.
Validation online protocols such as DQ, IQ, OQ, PQ, along with the associated VMP, URS, VRA, and
VP are usually written and reviewed electronically, however they are completed by hand and are manually signed and reviewed, and as such are not subject to 21 CFR Part 11 Review.
One of three approaches can be used by organizations to address the on-going Part 11 compliance requirements throughout the pharmaceutical and medical devices industries.
The regulation still permits the full submission of paper-based documentation. The issues with this approach include high costs, decreased quality, information storage availability, information retrieval ability, and the general portability of information.
The 21 CFR Part 11 regulation allows for the electronic records to be stored as equivalent to paper records with handwritten signatures executed. This approach still requires a large amount of printed documentation that carries the same risks and challenges as a full-paper approach, mentioned above, regarding compliance with the regulation.
This is the real intent of the 21 CFR Part 11 regulatory requirements. This approach increases product quality, saves money with automation of processes, establishes easy data storage and retrieval, provides ease data analysis and reporting, increases the portability of information, and diminishes or eliminates human error.
Regulatory Review, states that "the regulations in this part set forth the criteria under which the agency considers electronic records, electronic signatures, and hand-written signatures executed to electronic records to be trustworthy, reliable, and generally equivalent to paper records and hand-written signatures executed on paper".
A 21 CFR Part 11 review is implemented through a combination of compliant software, corporate policy and / or procedures. However the regulations are implemented, they must be accompanied by supporting documentation. The implementation of any FDA compliant system, whether software, policy or procedure oriented, is not valid without this documentation.
Data contained in documentation such as, the Installation Qualification (IQ), the Operational Qualification (OQ), the Validation Plan and Master Plan (VP & VMP), the Validation-risk-assessment (VRA), the Vendor Audit (VA), the Performance Qualification (P1Q), the Process Qualification (P2Q), the User Requirements Specification (URS), and Standard Operating Procedure (SOP) are normally held in hard copy and not considered as having to be 21 CFR Part 11 compliant.
Software systems used to implement the FDA regulations are the core component of a compliant system. Development of the software must be specifically aimed at satisfying the regulations’ requirements.
FDA specific features must include:-
Risk Mitigation in Validation template (Issue 11) $125.00 The Risk and Part 11 Validation Risk Assessment(VRA) protocol is becoming the most important document in the validation online train. The VRA reassures the regulators that you have looked at specific equipment functionality and considered the appropriate level of validation that is required. You have also considered various aspects of its use and the implications of any malfunctions. From the results of this exercise the scope of all validation activity can and must be justified. This is a robust and simple to execute document, one that will lead you through the process and deliver a result that can be used as the foundation for your Risk Mitigation in Validation template.
This VRA now includes the assessment table for categorizing and documenting the new 21 CFR Part 11 guidance ruling on what predicate data must be stored in a Part compliant system, along with the new broadsheet to establish your new database of part 11 records. (now mandatory).
This Pharmaceutical Validation combination protocol has been produced in response to several hundred reader suggestions we received in our ‘Suggestions Section’. It has been carefully designed to make it the preferred choice for Process and Laboratory stand alone equipment and associated standard operating procedure TEMPLATE. The associated medical device validation Master Plan template is interactive, easy to use and suitable for all mixes of equipment with and without software. Where temperature mapping is required it will included in this section. This of course may well be a Risk Mitigation in Validation risk Assessment template. As per 21 CFR Part 11.
The Installation Qualification Template or IQ section establishes documented verification that all medical device validation template online executables are catered for and that key aspects of the equipment Qualification adhere to approved design Qualification template and the recommendations of the manufacturer have been suitably considered. The Operational Qualification Template section establishes that there is documented verification that the installed system functions as specified and that there is sufficient documented process validation A executables to demonstrate this. The PQ section develops documented evidence that all the requirements specified in your corporate validation 4U manual have been verified as operating consistently and exactly as specified in the medical device validation template; The User Requirements Specification template
The Standard Operating Procedure template (SOP) used to generate this installation Qualification template (IQ), takes you through the process line by line, chapter by chapter. It really is unique to find a SOP document so easy to use, all the work is done for you. All the documents are detailed, all the drawings listed and all the checks and tests detailed. The final product is a professional and comprehensive Installation Qualification template. One that you can produce in less than 60 minutes. Yes, think about it, we all know how long producing IQ documents has taken in the past, whether for current Good Manufacturing Practice use medical device use or a simple installation qualification template.
You will find this validation online intuitive Operational Qualification template (OQ) delightfully simple and straightforward to use, as it takes you through the process of customization of your Operational Qualification Protocol template. Following the attached SOP will quickly and smoothly convert your template into an equipment specific 21 CFR Part 11 compliant Installation Qualification Template. The OQ template comes complete with all the standard test scripts, more specialist test scripts can be found listed below. These can easily be pasted into the standard OQ, allowing you to quickly build your own fully detailed and referenced company bespoke Operational Qualification Protocol, along with the installation qualification template.
All you need to do is follow the prompts in the
attached SOP. They will take you through the completion process section,
by section. At the end of this process your generic document has
progressed into a detailed, referenced, bespoke company document. The
document follows our three level URS system that ensures functionality
traceability from the URS to the various testing protocols. A great
document to author and use. This document interfaces with our Validation
Risk Assessment (VRA), Validation Online Project Plan (VP), User Requirements
Specification (URS), giving a seamless flow from your VMP through the VP - IQ -
OQ - PQ, while integrating flawlessly with the URS - DQ - VRA and verification of 21 CFR Part 11 compliance.
The Validation Plan (VP), is the starting point for any validation Online task, and the most important validation document. It improves validation efficiency greatly by forcing all concerned to document, review, and discuss, the proposed methods and allotted responsibilities. It is a mandated document with regulators and auditors.
While in the past validation was more focused on functions of procedures, recently the focus has progressed into infrastructure, networked systems and on security, authenticity and integrity of data acquired and evaluated by systems and data security, i.e. compliance with 21 CFR Part 11.