21 CFR Part 11

GMP 4, Annex 11
COMPLIANCE FOR CLOSED SYSTEMS OF
RADWAG-MANUFACTURED 3Y, 4Y, HY SERIES

CONTENTS
1. Introduction ............................................................................................................................................. 2
2. Definitions ............................................................................................................................................... 3
3. Analysis of Conformity of 4Y, HY Series Balances With Requirements of 21 CFR Part 11 ........................... 4
3.1. Subpart B - 11.10 Controls for Closed Systems................................................................................. 4
3.2. Subchapter B - 11.50 Signature Manifestations ..............................................................................13
3.3. Subchapter B - 11.70 Signature/Record Linking ..............................................................................14
3.4. Subchapter C Electronic Signatures................................................................................................15
4. SUMMARY ..............................................................................................................................................17

RADWAG
ADVANCED WEIGHING TECHNOLOGIES

1. Introduction
21 CFR Part 11, designed and published on 08.20.97, enables substitution of paper version documents with
electronic ones. This innovation aims to provide integrated, confidential and precisely correct electronic
documents and electronic signatures wherever required. FDA recognizes electronic signatures as equal to
handwritten signatures, provided that the electronic signatures and documents adhere to regulations of 21
CFR Part 11. Complete compliance requires actions to be taken within 3 various areas as defined below:

Technical verification 11.10 (a,b,c,d), is to be carried out by the manufacturer, who installs the
device. It aims to evaluate correctness of operation, control protections introduced to verify both
changes or access to various levels of application, and to enable verification of electronic signatures
and documents. All these actions are part of validation of a weighing system.

Procedural control 11.10 (e,f,g,h), is to be carried out by the user and it should cover Standard
Operating Procedures which refer to measurement process issues. The SOP procedures should not
be complicated, they must provide effective operation.

Administrative monitoring 11.10 (i,j,k,l) is to be carried out by the user, it covers issues such as
settings and parameters of both the device and the system. Administrative monitoring means also
staff trainings, control measures for access and distribution, procedures of control over changes
(introduced modifications).

A single device or a weighing system conforming to requirements of 21 CFR is a necessary but not sufficient
condition allowing to ensure conformity with 21 CFR Part 11. The manufacturer, or deliverer, is able to
provide equipment featuring functions providing adherence to 21 CFR Part 11. Nevertheless an institution
willing to implement weighing system accordant with 21 CFR Part 11 document, apart from purchasing a
respective device must also design and follow self-designed SOP. Additionally, as specified by 11.10 (i),
such institution must employ and provide respectively qualified staff (trained employees aware of
responsibility they take). Another crucial issue to be taken into account when speaking of adherence to 21
CFR is risk management (ICH Q), which risk management shall define requirements for both measurement
accuracy and need for conformity with 21 CFR Part 11.
When referring to the above information, it can be concluded that only those documents and records
which influence safety and product quality must strictly adhere to requirements of Part 11. Such approach
seems to be rational however in practice it is very rare and unlikely to apply so critical distinction between
documents especially within one closed weighing system.

2. Definitions
Definitions referring to 21 CFR Part 11:
a. Agency - means Food and Drug Administration.
b. Biometrics means a method of verifying an individual's identity based on measurement of the
individual's physical feature(s) or repeatable action(s) where those features and/or actions are both
unique to that individual and measurable.
c. Closed system means an environment in which system access is controlled by persons who are
responsible for the content of electronic records that are on the system.
d. Digital signature means an electronic signature based upon cryptographic methods of originator
authentication, computed by using a set of rules and a set of parameters such that the identity of
the signer and the integrity of the data can be verified.
e. 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.
f.

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.

g. Handwritten signature means the scripted name or legal mark of an individual handwritten by that
individual and executed or adopted with the present intention to authenticate a writing in a
permanent form. The act of signing with a writing or marking instrument such as a pen or stylus is
preserved. The scripted name or legal mark, while conventionally applied to paper, may also be
applied to other devices that capture the name or mark.
h. Open system means an environment in which system access is not controlled by persons who are
responsible for the content of electronic records that are on the system.

Requirements of 21 CFR are applied only when there is a need to achieve conformity for products
introduced into the USA market. 21 CFR is a document released by FDA. European Commission has
published a similar document, GMP (4) Annex 11, referring to computerised systems. Requirements of both
21 CFR and GMP (4) are practically likewise.

3. Analysis of Conformity of 4Y, HY Series Balances With Requirements of 21 CFR

Part 11
As it has already been mentioned, the fact that an institution owns weighing system adhering to
requirements of 21 CFR is not enough to allow the institution declare conformity with 21 CFR Part 11.
Radwag offers balances and terminals (3Y, 4Y, HY) which ensure achieving the said conformity. Regardless
of drastically different requirements and characteristics of particular working environments the main
features of Radwag weighing system remain stable. Read below sections to see how 21 CFR Part 11
requirements are adopted by Radwag weighing applications. The presented information refers to the
following paragraphs:

11.10
11.50
11.70
11.100
11.200
11.300

Subpart B Controls for closed systems.

Signature manifestations
Signature/record linking
Subpart C General requirements, electronic signatures
Subpart C Electronic signature components and controls
Subpart C Controls for identification codes/passwords

Complete conformity with 21 CFR Part 11 is ensured by the following: mechanisms implemented on a
balance, SOP procedures, administrative procedures being a part of quality management system. The
above statement refers to all measuring systems regardless of measured quantity.

3.1. Subpart B - 11.10 Controls for Closed Systems

TECHNICAL VERIFICATION
CFR 21 (11.10)
Persons who use closed systems to create, modify, maintain, or transmit electronic records shall employ
procedures and controls designed to ensure the authenticity, integrity, and, when appropriate, the
confidentiality of electronic records, and to ensure that the signer cannot readily repudiate the signed
record as not genuine. Such procedures and controls shall include the following:
CFR 21 (11.10.a)
Validation of systems to ensure accuracy, reliability, consistent intended performance, and the ability to
discern invalid or altered records.
All Radwag measuring systems are designed with reference to strict requirements of ISO 9001
introducing, among many, regulations for designing and production. The regulations guarantee reliability
and functionality of each system, which system may of course be optimised in order to meet unique
requirements of a particular working environment. Any activity of any user of the system gets recorded
in an Audit Trail file, the file may be freely overviewed. For selected options (user, procedure, event etc.)
it is possible to sort some of the recorded data. Each crucial electronic record subjected to requirements
of 21 CFR Part 11 is registered, stored and protected. Such record may be compared with paper (printed)
version, it can be also previewed on-line. In order to access the system, respective access level is needed.
This solution allows to protect electronic records.
The above described features facilitate successful completion of a validation process. Radwag offer
comprises validation process performance.

CFR 21 (11.10.b)
The ability to generate accurate and complete copies of records in both human readable and electronic
form suitable for inspection, review, and copying by the agency. Persons should contact the agency if
there are any questions regarding the ability of the agency to perform such review and copying of the
electronic records.
In Radwag measuring systems of 4Y series all single records related to the weighing process are recorded
in balance database, access to which is protected by use of passwords and respective access levels. Any
data can be printed or exported at any time in format read by a spreadsheet program. Report (list of
weighings) is permanently stored in reports database (controls database). Each document of this type
can be printed or exported in its original form.

Fig. 1. Weighings database, available options: data search, results export

Fig. 2. Database structure Controls (reports)

Each report consist of three parts:

Header, a programmable section which may comprise: date, time, balance serial
number, operators name. The header may also feature so called non-standard printout,
i.e. self-designed text or alphanumeric information.
Weighing data content, section which may comprise: measurement results, measuring
series, differential weighing results, SQC information. Result of a single weighing not
related to any specific samples name may also be displayed here. In order to specify
origin of such unrelated weighing, an appropriate text field (printout-displayed) is used.
Footer, contents of footer and header sections are likewise.

The above presented layout is just one of numerous options, the electronic document may comprise
freely selected components. Regardless of applied layout, each document features an electronic
signature.

Fig. 3. Report: header line footer layout

CRF 21 (11.10.c)
Protection of records to enable their accurate and ready retrieval throughout the records retention
period.
All data is permanently stored in a database. Database content can be periodically archived on a freely
selected device in accordance with adopted time schedule. It is possible to overview and analyse each
archived period using computer application. The user may specify which records or reports are to be
analysed. Data recorded on external storage devices can be analysed using Excel program for example.

Fig. 4. Saving report to a database, option of printout and export enabled

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CFR 21 (11.10.d)
Limiting system access to authorized individuals.
Upon start-up, the weighing system although active requires logging in. Each user has unique access code
to the system. There are four access levels:

guest

user

advanced user

administrator
Each access level permits the user to carry out particular set of operations, e.g. printing, settings
modification, designing printouts, designing methods, etc.

Fig. 5. Access to the weighing system

PROCEDURAL CONTROL
Persons who use closed systems to create, modify, maintain, or transmit electronic records shall employ
procedures and controls designed to ensure the authenticity, integrity, and, when appropriate, the
confidentiality of electronic records, and to ensure that the signer cannot readily repudiate the signed
record as not genuine. Such procedures and controls shall include the following:
CFR 21 (11.10.e)
Use of secure, computer-generated, time-stamped audit trails to independently record the date and
time of operator entries and actions that create, modify, or delete electronic records. Record changes
shall not obscure previously recorded information. Such audit trail documentation shall be retained for a
period at least as long as that required for the subject electronic records and shall be available for
agency review and copying.
All weighing system changes are registered by co called Audit Trail. Parameters Editor PC software is a
tool allowing analysis (readout) of the registered information. Parameters readout may be carried out
directly, it is possible when connection has been established between the balance and the program
(Ethernet, RS 232). Otherwise Audit Trail Export option must be used (Misc. submenu). Exported file
name consists of date, time and successive number.

Fig. 6. EP program information on system modifications

Fig. 7. Analysis of system changes export of data to external storage.

CFR 21 (11.10.f)
Use of operational system checks to enforce permitted sequencing of steps and events, as appropriate.
Radwag measuring system is a system in which sequence of events for all editing and weighing processes
has been planned. Each process may, but does not have to, use input data. There are two factors
determining to what extend input data is used, the user and the applied weighing method. The main
part of the weighing process may be single measurement, series, comparison, formulation process etc.
Upon completed measurement all data is saved, printed or exported. Measuring processes based on
methods such as:
- series of measurements
- differential weighing
- formulations
- comparison
enforce particular sequence of operations which cannot be altered. When carrying out measuring
processes that are not based on any particular method the sequence of operations and events shall be
accordant with SOP regulations reflecting process and system requirements.

Fig. 8. Sequence of operations in 3Y-4Y- HY10 system

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CFR 21 (11.10.g)
Use of authority checks to ensure that only authorized individuals can use the system, electronically sign
a record, access the operation or computer system input or output device, alter a record, or perform the
operation at hand.
Measuring system of 3Y, 4Y, HY 10 series is protected by multi-level authorization system. Each operator
is assigned with particular access level and an individual account accessed by a password. System
administrator manages the accounts and rights of particular operators. In the course of the first logging
in password change is required. Such requirement is one of many safety precautions preventing
unauthorised access.

Fig. 9. Authorization control

CFR 21 (11.10.h)
Use of device (e.g., terminal) checks to determine, as appropriate, the validity of the source of data input
or operational instruction.
In a closed system of 3Y, 4Y, HY 10 series, all input data is entered to the system by an operator. Entered
data range depends on operation method requirements. Most of the data to be entered is selected from
a certain data set. An attempt to enter any out of range data is clearly signalled to the operator thus
entering too low or too high values is prevented.

Fig. 10. Control of system information

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ADMINISTRATIVE MONITORING
CFR 21 (11.10.i)
Determination that persons who develop, maintain, or use electronic record/electronic signature
systems have the education, training, and experience to perform their assigned tasks.
Continuous increase of professional qualifications is an
inevitable element of development of each quality
system. Radwag offers trainings providing the
participants with knowledge on typical applications and
dedicated system solutions. Participation is always
confirmed with an appropriate certificate. Activity
within this area is covered by ADMINISTRATION-related
operations performed by people monitoring the
measuring system.
CFR 21 (11.10.j)
The establishment of, and adherence to, written policies that hold individuals accountable and
responsible for actions initiated under their electronic signatures, in order to deter record and signature
falsification.
Quality management system is a fundamental issue enabling a particular organization to win customers
trust. It combines basic system elements and dedicated procedural solutions enabling the company to
establish specified goals.

CFR 21 (11.10.k)
Use of appropriate controls over systems documentation including:
1) 1) Adequate controls over the distribution of, access to, and use of documentation for system
operation and maintenance.
2) 2) Revision and change control procedures to maintain an audit trail that documents timesequenced development and modification of systems documentation.
System related documents shall cover any issues concerning operation of the weighing system, i.e.
technical control, periodical calibration and tests checking the functionality. Radwag offers the above
listed services for each weighing system.

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3.2. Subchapter B - 11.50 Signature Manifestations

CFR 21 (11.50.a)
Signed electronic records shall contain information associated with the signing that clearly indicates all
of the following:
1) The printed name of the signer;
2) The date and time when the signature was executed; and
3) The meaning (such as review, approval, responsibility, or authorship) associated with the signature.
Every single weighing record, confirmed by PRINT button, is saved to the database. It is associated with
currently logged in operator and product (providing that product has been selected). Report on weighing
or weighing series is more advanced solution. Such report comprises sections selected by an operator
(header - footer), see Fig. 3. The report is generated automatically for all weighing methods (statistics,
SQC, differential weighing, formulations, etc.). When performing series of weighings not referred to any
particular method it is necessary to use Reports Hot-Key. The operator can define weighing series
parameters and name the series upon completion.
Each report is saved to reports database where it gets stored permanently. The report can be signed
(author) or verified (supervisor). The signature is not obligatory, but it is advisable to use it with
documents which influence quality and safety when it comes to production and control process.

Fig. 11. Record of single measurement in a database

Fig. 12. Reports Hot-Key menu

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Fig. 13. Preview of database-stored report option of signature (verification) enabled

CFR 21 (11.50.b)
The items identified in paragraphs (a)(1), (a)(2), and (a)(3) of this section shall be subject to the same
controls as for electronic records and shall be included as part of any human readable form of the
electronic record (such as electronic display or printout).
All changes, also those concerning electronic records, are recorded permanently. The changes can be
analysed using Audit Trail file.

3.3. Subchapter B - 11.70 Signature/Record Linking

Electronic signatures and handwritten signatures executed to electronic records shall be linked to their
respective electronic records to ensure that the signatures cannot be excised, copied, or otherwise
transferred to falsify an electronic record by ordinary means.
Nature of the Radwag weighing system does not allow linking of handwritten signatures or their transfer
from one electronic document to another. Information concerning the signatures, documents, signed or
verified records is prevented against editing therefore it cannot be modified. Audit Trail file displayed by
EP program is also prevented against edition. It can be only sorted or exported.

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3.4. Subchapter C Electronic Signatures

CFR 21 (11.100.a) General requirements
Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to,
anyone else.
Each operator has an individual name, code and password. The system controls stored data and
prevents use of two identical names or codes.

CFR 21 (11.200.a) Electronic signature components and controls.

Electronic signatures that are not based upon biometrics shall:
(1) Employ at least two distinct identification components such as an identification code and
password.
(i) When an individual executes a series of signings during a single, continuous period of
controlled system access, the first signing shall be executed using all electronic signature
components; subsequent signings shall be executed using at least one electronic
signature component that is only executable by, and designed to be used only by, the
individual.
(ii) When an individual executes one or more signings not performed during a single,
continuous period of controlled system access, each signing shall be executed using all of
the electronic signature components.
(2) Be used only by their genuine owners; and
(3) Be administered and executed to ensure that attempted use of an individual's electronic
signature by anyone other than its genuine owner requires collaboration of two or more
individuals.
User-related data provides the following: name, code, password, first name and last name, permissions,
status of the account, menu language, profile, RFID card ID. When logging in it is necessary to confirm
identity by entering access code.

CFR 21 (11.200.b) Electronic signature components and controls.

Electronic signatures based upon biometrics shall be designed to ensure that they cannot be used by
anyone other than their genuine owners.
Closed weighing systems of 4Y series and systems based on HY 10 terminals do not offer verification
mechanisms based upon biometrics. Nevertheless such control mechanisms can cooperate with Radwag
closed system via respective program interfaces.

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CFR 21 (11.300) Controls for identification codes/passwords.

Persons who use electronic signatures based upon use of identification codes in combination with
passwords shall employ controls to ensure their security and integrity. Such controls shall include:

CFR 21 (11.300.a)
Maintaining the uniqueness of each combined identification code and password, such that no two
individuals have the same combination of identification code and password.
The weighing system meets the above requirement with use of internal control mechanisms. System
administrator is not authorised (has no power) to influence system operation as far as control
mechanisms are concerned.

CFR 21 (11.300.b)
Ensuring that identification code and password issuances are periodically checked, recalled, or revised
(e.g., to cover such events as password aging).
Systems administrator can activate or deactivate the accounts permanently. Deactivation period is not
controlled by the weighing system and this is why it should be conditioned by system for quality
management (e.g. ISO).

Fig. 14. Account activation

CFR 21 (11.300.c)
Following loss management procedures to electronically deauthorize lost, stolen, missing, or otherwise
potentially compromised tokens, cards, and other devices that bear or generate identification code or
password information, and to issue temporary or permanent replacements using suitable, rigorous
controls.
Radwag weighing system does not allow operator identification to be carried out with use of external
devices. In the course of the logging in operation unique code and passwords are required.

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CFR 21 (11.300.d)
Use of transaction safeguards to prevent unauthorized use of passwords and/or identification codes, and
to detect and report in an immediate and urgent manner any attempts at their unauthorized use to the
system security unit, and, as appropriate, to organizational management.
Logging in operation can be carried out numerous number of times. It is not specified how many
attempts are allowed. Attention shall be paid to the fact that in case of Radwag, a weighing device and a
system is one and the same thing, used for mass measurement. Unauthorized use may result with
performance of accidental weighing unrelated with the manufacturing process, not influencing
production safety or risk level in the course of the said process. Balance-stored databases, reports, etc.
are accessed upon logging into the system.

Fig. 15. Protection against interference of unauthorized persons

4. SUMMARY
Closed measuring systems such as 3Y, 4Y series balances or HY 10 terminals can be operated wherever
compliance with 21 CFR Part 11 is required. Compliance with 21 CFR Part 11 requires conformity to EU
GMP Annex 11. Relevant provisions of Annex 11 define computerised system as a set of software and
hardware components which together fulfill certain GMP-specified functionalities. When it comes to 3Y,
4Y, HY 10 the said components are in-built elements and along with the balance they constitute one
integral device.

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