Ultimate Guide: How to Comply with FDA 21 CFR Part 11
Those in the pharmaceutical, biotech, cosmetic, food and beverage, and other FDA-regulated industries work hard to ensure their organizations and products are in a state of perpetual advancement and improvement. Those in these industries design and produce often life changing products that are often at the forefront of technological advancements. Because the work conducted by organizations in these industries can be so personally impactful and crucial, proper document processes and workflows that are also FDA compliant are essential. This is where electronic signatures come in.
For those organizations who must follow FDA regulations, 21 CFR Part 11 compliance is no stranger. 21 CFR Part 11 is an FDA-published regulation that establishes the rules and requirements for companies to follow when it comes to electronic records. This has become an increasingly important regulation in recent years as organizations continue to increase their usage of convenient digital documents and electronic signing.
What is 21 CFR Part 11?
In the U.S, organizations in the pharmaceutical, biotech, cosmetic, food and beverage, and other related life science industries are moderated and regulated by U.S. Food and Drug Administration (FDA). Regulation is imperative for these industries as they are often directly linked to public health and, more so, the production of life-saving drugs. These regulations can be of particular importance when it comes to paperwork, forms, and documents that are utilized within FDA-regulated industries.
Using digital documents and electronic signatures is becoming increasingly more frequent in FDA-regulated industries. The FDA has determined that while adherence to compliance with ESIGN and UETA is essential, there are further guidelines that also must be followed. 21 CFR Part 11 is an FDA regulation that outlines compliance requirements for electronic signatures and electronic records in these industries.
This FDA regulation has two fundamental areas of enforcement: electronic signatures and electronic records. It applies to all areas of the CFR’s 21st Title for all medical products and manufactured drugs distributed in the U.S.
The decoding of the phrase “21 CFR Part 11” is as follows:
- “21” – This represents the 21st Title of the Code of Federal Regulation (CFR). Usually, this title outlines the rules of the FDA and is divided into three chapters.
- “CFR” – This stands for “Code of Federal Regulations.” Generally, this is a coded set of administrative laws. That is, the codification of the permanent and general rules published in the Federal Register.
- “Part 11” – This outlines the guidelines to follow that regulate the e-signatures and electronic records pertinent industries.
A History of FDA 21 CFR Part 11
Earlier in the 21st century, when computer usage and digital processes were becoming more common for businesses, there was confusion on how those in biotech, pharmaceutical, food and beverage, cosmetic, and other life science industries were to follow the 1997 issued FDA Title 21 CFR Part 11 rule pertaining to electronic signatures and records. To clarify usage and regulation adherence, the FDA released it’s 2003 Guidance for Industry Part 11, Electronic Records: Electronic Signatures.
Unfortunately, there were contradicting aspects of this guidance release by the FDA. While there were was a general appreciation of clarification of this FDA rule, there was coinciding frustration by companies who experienced issues due to contradictory guidance given. This resulted in the FDA releasing a clarified and final version of 21 CFR Part 11 in 2007.
Who Must Comply with 21 CFR Part 11 Guidelines?
The entire FDA-regulated industry, which includes food & beverage manufacturers, pharmaceuticals, cosmetics companies, biotech, and medical device manufacturers, must comply with 21 CFR 11 rules.
It is also required that computer systems which support and report data for FDA-related purposes, or that produce or store data used to make quality control decisions related to the aforementioned industries, should comply with 21 CFR 11 laws. This includes any lab results used to establish quality, strength, purity, safety, or efficacy as related to public health. In the manufacturing setting, this will include all data used to formulate decisions linked to product quality and product release that can impact public health.
The Definition of Electronic Signatures and Electronic Records
The 21 CFR 11 defines electronic signatures and records in the following manner:
- “Electronic record means any combination of text, graphics, data, audio, pictorial, or other information representation in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system.
- Electronic signature means a computer data compilation of any symbol or series of symbols executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual’s handwritten signature.”
Electronic Records that Come Under the Scope of 21 CFR Part 11 Include (but may not be limited to):
- All electronic records which are maintained or submitted to the FDA as part of predicate rules. (A predicate rule is one rule that is outlined in the Public Health Service Act and the Federal Food, Drug, and Cosmetic Act apart from the 21 CFR 11.)
- All electronic records that are generated pertaining to the Current Good Manufacturing Practice (CGMP) program for animal and human drugs and biologics.
- All electronic records which are maintained besides the paper records and are used for regulated activities.
- Copies of electronic records that are used in regulatory activities
- All electronic records which are meant to be maintained in line with the statutory requirements of the FDA in an electronic format, albeit not expressly identified in the regulations.
In-summary, any FDA-regulated company that opts to maintain or submit records to FDA in electronic form, must comply with the 21 CFR 11 requirements.
Use Cases for How E-Signature Solutions Can Benefit Those In the Pharmaceutical Industry
The pharmaceutical industry is one of the largest followers of 21 CFR Part 11 and, therefore, can benefit greatly from the implementation and use of 21 CFR Part 11 compliant electronic signatures, like those from Foxit eSign (formerly Foxit eSign). Here are some examples:
Production workflow
A pharmaceutical company’s production department needs to check and authenticate all pre and post-production steps before everything can move onto the next phase. Generally speaking, the production department must ensure that:
- All the environmental parameters pertaining to manufacturing stations are in perfect control before the production process commences. This could be the differential pressure, temperature, or the general hygiene of the manufacturing station. These things must be monitored, documented, and verified before the process starts.
- Likewise, a production executive should ensure that the raw materials used in the manufacturing have been examined by the department manager and Quality Assurance (QC) officer. It is a mandatory requirement before these materials can be conveyed to the manufacturing station for processing.
- Similarly, the production department needs to ensure that the QC department frequently analyzes the samples of the manufactured batches. This also guarantees that the manufacturing process meets all the quality requirements.
- Lastly, when the manufactured products need to be transferred to the packing department, they again require documents of approval from the manufacturing and packaging department.
These are just a few stages of production workflow, which need some form of validation and documentation for the process to go on flawlessly. If a document goes missing or any of the signing parties are not present at the site, it can bring the entire process to a halt.
This is where e-signatures can help.
Managers and executives can authenticate a production step and the related pre-requisites by e-signing documents from an off-site location. For example, suppose a QA officer forgets to verify the raw materials identification process. In that case, all the relevant documents can be posted on the organization’s portal, from where they can be easily e-signed by another senior employee. The staff at the production department won’t have to wait for the QA officer simply to get the record authenticated to commence the production process.
Procurement workflow
This is an area that can be reviewed either on the inter-departmental level or macroscopic level:
- In a pharmaceutical manufacturing setting, testing tools like moisture meter should be calibrated by external agencies to make sure that the integrity of the manufacturing station is not compromised. For instance, a meter, calibrated by a compliant agency, should have an authenticated gate-pass before being used in a manufacturing station. A missing signature can slow this process, which eventually affects the production process.
- In a different example, the production division may need to file an urgent procurement request for a critical product in the manufacturing process. Usually, this request needs to be authorized by the procurement office or manager. If any of these people are missing, it can delay the procurement process.
- Similarly, there could be a scarcity of packaging material. An unsigned invoice relating to the purchase of these materials can again slow down the process and negatively impact the company’s operations.
This is where electronic signatures can help.
Through electronic signature practices, pharmaceutical companies can streamline the document flow governing the procurement process. This is made possible by speeding up the signature capturing efforts and ensuring that every required field that needs to be filled is not left blank.
Other Ways E-Signature Solutions like Foxit eSign Can Benefit FDA-Regulated Industries
Improves Sales and Sample Management
From 21 CFR Part 11 to HIPAA to Prescription Drug Marketing Association (PDMA), there are stringent requirements that oversee pharmaceutical sampling. Appending signatures is costly and time-consuming, especially when done manually. Thanks to Foxit eSign, sales teams can easily collect signatures online and from any internet-enabled device. Meaning, regardless of where a customer is situated, a sales or sample transaction can take place.
Sensitive Information Is Secured
Security can be a weighty concern for those in the pharma, biotech, or other FDA-regulated industries. Often, manufacturing uses proprietary or secret information, which should be kept confidential. And as you might be aware, paper records have endless security issues.
Investing in Foxit eSign software offers organizations a sophisticated alternative to keep their documentation secure. From limiting access to certain users to password-protecting sensitive documents and restricting when and where a document can be edited or signed, Foxit eSign does it all.
With so much at stake, in case of inaccuracies, making sure that the correct person signs off on the relevant process is imperative. Unlike wet ink signatures which are vulnerable to forgery, electronic signatures powered by Foxit eSign are tamper-proof and guarantees a comprehensive audit trail.
Foxit eSign Meets Industry Regulations
Foxit eSign works with industry specialists to guarantee the most reliable and secure e-sign technology and processes. Foxit eSign supports compliance with FDA 21 CFR Part 11, including iOS and web devices. It also supports HIPAA compliance, SOC 2 Type II, ESIGN, and eIDAS acts. Most importantly, Foxit eSign has system audit tools to monitor document history and protect you from phishing attempts or cyber-attacks.
Integrates with Current Technologies Easily
Foxit eSign integrates easily with popular technologies such as manufacturing management software, claims processing software, recruitment and staffing software, accounting software, document management software, to name a few. Thus, FDA-compliant companies using applications like Fishbowl, Dropbox, NetSuite, Intellect eQMS, or BatchMaster ERP, can rest assured knowing that Foxit eSign can complement their existing systems adequately.
Functionality in Various Languages
In its pursuit of fresh discoveries, the pharmaceutical, biotech, cosmetic, food and beverage, and other related organizations often span national borders and languages. The fact that Foxit eSign offers functionality in 12 languages and accepted in 60+ countries confirms how determined it is to serve these industries.
For instance, with Foxit eSign, a medical researcher in Italy can share information with a partner in a Spanish-speaking country or a potential venture capital founder in the U.S.
What happens If You Don’t Comply with FDA 21 CFR Part 11?
If an organization doesn’t abide by the 21 CFR Part 11 regulations, it will come to the FDA’s attention and can mean serious fines or other sanctions. The FDA carries out regular inspections; if they find issues relating to non-compliance, they may issue the company in question a Form 483, or “Notice of Inspectional Observations.” Essentially, this is a warning demanding that the company in question rectifies the ascertained concerns. Take into account, these are general forms, and most of the infringements documented have nothing to do with the 21 CFR 11 guidelines.
Following the issuance of a Form 483, recipients have 15 days to respond to the FDA. When or if an organization doesn’t respond to a Form 483, or if the organization doesn’t properly address or correct the issue that is noted as being non-compliant, the FDA will determine if further action is suitable.
Tips for Complying with 21 CFR Part 11
As far as regulatory compliance for FDA-regulated companies goes, misunderstanding around 21 CFR 11 is common. Unfortunately, it’s common for companies to think they are compliant, but, in reality, they are not. Take a look at these helpful tips for complying with 21 CFR Part 11:
First, determine whether Part 11 applies to your organization
According to the FDA’s guidance for 21 CFR Part 11, this regulation applies to records of FDA-compliant companies as follows:
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- Records that are used in place of paper documents
- Records that are used in addition to paper documents
- Records that are submitted to the FDA in electronic format
- Electronic signatures used in the place of pen-and-ink signatures
Follow FDA guidance on using electronic signatures
For electronic signatures to be compliant under 21 CFR Part 11, companies should ensure the following:
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- The date and time the signature is made are present
- The printed name of the signer is present
- The signer has a unique signer ID
- Digital signature technology is used
- The reason for the signature is clearly stated on the documentation
- All ESIGN and UETA compliances are followed
Foxit eSign (formerly Foxit eSign) allows companies to meet these requirements so that they can ensure easier and more thorough 21 CFR Part 11 requirements.
Establish clear audit trails for transparency and traceability
Clear audit trails are needed so that organizations can view which party performed any given action and when actions where taken; this includes when records were created, changed, deleted, sent, or made obsolete.
All events must be documented in detail for documents to be compliant with FDA 21 CFR Part 11. Besides change management, audit trails also apply to moments of access. Organizations should always be informed when users are logging in and out. One may refer to it as a “comprehensive history of your record-keeping system.”
With an audit trail, the FDA can easily inspect FDA-compliant organization’s records. The quicker it is to locate past records, the smoother your inspection can be.
The information on this page does not constitute legal advice or any guarantees from Foxit eSign (formerly Foxit eSign); it is to be viewed as information pertaining to how FDA-compliant companies may use Foxit eSign (formerly Foxit eSign) electronic signature software as a tool for maintaining compliance. It is always recommended that those who must comply with FDA 21 CFR Part 11 requirements consult with FDA guidance or legal counsel to ensure proper FDA compliance for their organization.
Foxit eSign eSignature is compliant with FDA 21 CFR part 11.
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