Fundamentals of 21 CFR Part 11

21 CFR Part 11 is one of the regulations which regulates electronic records and electronic signatures in the food and drug industry in the USA. This law is enforced by the US FDA, which is a government agency responsible for public health, in various ways. 21 CFR Part 11 widely applies to the Pharmaceutical industry when compared to the food industry.

The pharmaceutical industry is making wonderful progress with the advent of new technologies into drug research and manufacturing. There is no doubt that information technology has been converted into the main pillar of the drug industry. Revolutionary changes in data recording and preserving of records, allowed the pharmaceutical industry to automate the things in a broad range.

Computerization of manufacturing processes, saving the time and money of the company in large amounts and at the same time, it is bringing forth the transparency in the manufacturing activities of medicinal drugs. As a result, the use of electronic records is increasing gradually in the medicinal drug industry. In this context, it is necessary to control the quality, reliability and accuracy of the electronic records.

What is 21 CFR Part 11?

The pharmaceutical industry is directly controlled by the government, in any country on the globe, since it produces life-saving drugs and linked with public health. In the USA, the government made certain rules and regulations to control the pharmaceutical industry.

21 CFR Part 11 is one of the regulations which regulates electronic records and electronic signatures in the food and drug industry in the USA. This law is enforced by the US FDA, which is a government agency responsible for public health, in various ways.

The decoding of the term '21 CFR Part 11' is as follows:

21 - 21st Title of the Code of Federal Regulations
This title defines the rules and regulations of the Food and Drugs Administration and divided into three chapters.

CFR - Code of Federal Regulations
This is administrative law, i.e., the codification of the general and permanent rules published in the Federal Register.

Part 11 - 11th part of the Chapter-I
This defines the regulations to follow to regulate the electronic records and electronic signatures in the food and drug industry. 

The final Part 11 requirements, which were issued by the US FDA, became effective since August 1997.

Read: Basics of US FDA - Things You Must Know

What Are Electronic Records and Electronic Signatures?

21 CFR Part 11 widely applies to the Pharmaceutical industry when compared to the food industry. Why, because the use of high-end technologies in the manufacturing of medicinal drugs and the amplitude of the computerization is very large in this industry.

The drug manufacturing process contains a variety of activities. Raw materials procurement, synthetic reactions, milling, drying, pulverization, crystallization, process validations, laboratory testing, analytical test method validations, packing and labelling, product storage and distribution, marketing, financial transactions and R&D activities are just a few examples.

It is a necessary and a statutory requirement to record or document the activities performed during the manufacturing of a medicinal product. The records can exist either in a paper format or electronic format. The agency evaluates the drug's quality, during its inspection, based on these records only. Hence, the quality, reliability and accuracy of the records are very very important.

The 21 CFR Part 11 defines the Electronic Record and Electronic Signature in the following way:

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

Read:
Basics of Data and Data Integrity - Very Very Important
Data Integrity As Per 21 CFR - You Should Know Now

Which Records Are Considered As Part 11 Electronic Records?

You know well that the generation of electronic records has a certain process. These records are generated by using different software and firmware programs during the manufacture of medicinal drugs.

Pharma companies may be recording the information of many regulated activities in an electronic format to save money and time.

These electronic records can be modified, processed, maintained, archived, retrieved or transmitted based on the need.

So, to protect the originality of the records and to prevent the data tampering, specific requirements have been set forth in 21 CFR Part 11.

The following electronic records come under the scope of 21 CFR Part 11:

1. All electronic records which are generated as part of current good manufacturing practice (CGMP) initiative for human and animal drugs and biologics.


2. All electronic records to be maintained as a part of the statutory requirements and submitting information to FDA in an electronic format even though they have not specifically identified in the regulations.


3. All electronic records that you are maintaining or submitting to the agency as part of predicate rules.
   A predicate rule is one that which is set forth in the Federal Food, Drug, and Cosmetic Act (the Act) and the Public Health Service Act (the 29 PHS Act) apart from 21 CFR Part 11.


4. All electronic records that you maintain in addition to the paper records and use them for the regulated activities.
   
   
   Example: Suppose you are using a master electronic template of Batch Processing Record (BPR) to take printout and recording the information on the paper record. In this case, the paper record comes under the category of cGMP record and the master electronic template shall be considered as Part 11 electronic record. Why, because you are repeatedly using the same template to take the printout and generating paper records for different batches or lots. Here the integrity of master copy is very important and the changes of the template must be controlled.


5. Copies of all electronic records which are used in regulatory activities.

The above criteria for Part 11 records conclude that if you choose to maintain or submit your records to FDA in an electronic format, you must comply with the 21 CFR Part 11 requirements.

Read: How To Control Data Integrity Issues In The Pharmaceutical Industry?

Which Records Are Not Considered As Part 11 Electronic Records?

Pharmaceutical Industry has some concerns in maintaining the electronic data as it is increasing the expenditure of the company. So, the USFDA considered their concerns and issued a guidance document "Guidance For Industry - Part 11, Electronic Records; Electronic Signatures — Scope and Application". In this document, it is specifically stated which records will not be considered as Part 11 electronic records.

The following electronic records will not come under the scope of 21 CFR Part 11:

1. The electronic record which is used only for the purpose of generating a paper printout. In this case, you are not using the electronic record for regulated activities; only the paper record is used for regulated activities. Hence, this paper document falls under the category of regulated document. This document must meet all the applicable predicate rules.
   
   
   Example: The USFDA asked you for the trend of an unknown impurity in a particular product as part of Drug Master File (DMF) review.
   
   Normally, what would you do to respond to the query? You will collect the impurity results from a certain number of batches and put them into word or excel spreadsheet to make a table which summarizes the trend. Then you will take a printout of that electronic document and put a signature on it as per the cGMP requirements to make the document an authentic one.
   
   Here, you are not using the word or excel spreadsheet to communicate the USFDA. You are sending the requested information only through a paper record. Therefore, word or excel spreadsheet, which you created in this case, would not be considered as Part 11 electronic record.


2. All the electronic records which themselves are not submitted to the Agency, but used in generating the regulated documents as part of regulatory submissions, are not Part 11 electronic records. However, review and ensure your decision before arriving at a conclusion that the particular electronic records are not required to maintain in an electronic format under a predicate rule.

You must be careful while judging an electronic record's scope, i.e., carefully decide whether it is under the scope of Part 11 or not. You must thoroughly refer the predicate rules before taking such a decision. Otherwise, you will land in a non-compliance environment.

Use of Electronic Signatures

In today's digital world, the use of electronic signatures is helping the pharmaceutical industry a lot. If you use electronic signatures in regulated activities, it is essential to exercise the controls over its use.

An electronic signature is used in the pharmaceutical industry for various transactions. Generally, it is used to provide an individual's acceptance (such as approved, reviewed, and verified) to the electronic records which are generated as per the requirements stated under the predicate rules.

Your electronic signature is equivalent of your handwritten signature only when it meets all the Part 11 requirements of Electronic Signatures.

Your electronic signature shall be unique. It must not be reused by or reassigned to, anyone else.

Your electronic signature binds you legally for all your transactions performed in a regulatory environment.

Implementation of 21 CFR Part 11

Even though the Part 11 requirements came into effect a long back, still the pharma industry is raising its concerns to the FDA on the part of the implementation. Why, because the maintenance of electronic records influences the cost of the medicines and expenditure of the company. The main concerns came from the industry are related to the validation, audit trails, record retention, record copying, and legacy systems.

Hence, FDA currently reexamining the Part 11 requirements, but the exercise not yet finished. Anyhow, right now the current Part 11 requirements will apply as such and there are no exclusions/exceptions.

The first thing you need to do is to identify the electronic records that you are maintaining and submitting to the Agency under predicate rules. Then you determine and classify which are Part 11 records and which are not.

Document the classification of your electronic records in a form of Standard Operating Procedure (SOP), i.e., create a document which officially declares what is Part 11 record and what is not. As a matter of fact, the pharmaceutical company must have clarity on which type of record format it is going to rely to perform regulated activities.

Once you got the clarity on your electronic records that to be maintained in line with the regulations, design the controls and take security measures to protect the data integrity. Take initiatives to meet the Part 11 requirements.

Read: How To Prevent Data Integrity Issues In Pharma QC Lab?

Summary

Compliance with 21 CFR Part 11 is an essential thing to fulfil if you want to enter into the US market.

Part 11 applies to all electronic records, which are generated as part of regulatory activities, in your company.

US FDA very clearly defined all its requirements of electronic records in 21 CFR Part 11 and those are applicable if you create, modify, archive, retrieve or transmit electronic records under any records requirements set forth in Agency regulations.

Classify your electronic records into Part 11 and non-Part 11 records to reduce your expenditure on electronic data management.

Be careful while doing the classification and thoroughly refer the predicate rules before proceeding for the activity.

Your electronic signature is valid in a regulatory environment only when it meets the 21 CFR Part 11 requirements.

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Author Profile

Ram Kumar Reddy

Ram Kumar Reddy is the founder of Pharma Times Now. Helping Pharmacy and Chemistry students, along with the pharma employees, in learning pharmaceutical science. He has 24 years of rich experience in the Pharmaceutical industry and well versed in quality systems. He worked with Dr.Reddys and Sai Life Sciences. He lives in Hyderabad, India.