G-208

Analytical Calibration and Equipment Control

Section G — Equipment Revision 0 13 pages

Original Document

Scanned document (image-only PDF)

Extracted Text

Searchable text extracted from PDF

1.0 Purpose

The objective of the Calibration and Equipment Control process for analytical instruments is to

ensure that laboratory monitoring and measuring equipment is appropriately calibrated or
verified to ensure the equipment's continuing suitability for use and accuracy of measurements.
Another objective is to ensure that maintenance is performed on test equipment to ensure
proper functioning.

2.0 Scope

This procedure applies to the analytical control system for the calibration or verification and
maintenance of all analytical monitoring and measuring equipment and materials used to
perform laboratory activities and generate analytical results. This procedure also ensures that
such equipment is used in a manner that is consistent with measurement requirements for the

specifications relevant to the laboratory activities concerned. This procedure also applies to the
maintenance of analytical equipment which does not require calibration and software used for
accredited testing activities.

3.0 Responsibility

3.1 This procedure applies to all employees who use analytical measuring equipment to
assess samples for testing finished products, raw materials, or any other samples for a
GMP purpose.

3.2 The definition, implementation and maintenance of the calibration system is the
responsibility of the Analytical Development Manager, who oversees the Calibration

and Equipment Control process.

3.3 The Analytical Development Manager is responsible for and maintains the Calibration
Database, calibration certificates, records of calibration and verification activities,
maintenance and/or qualification schedules and records of maintenance and
qualification activities.

3.4 Personnel who suspect measuring equipment needs calibration or verification or

equipment used for testing needs repair or maintenance are responsible for submitting it
to, or bringing it to the attention of, the Analytical Development Manager.

[SOP

Sttaann dard Op Operating g P Procedure SpOaP pNo | Reev v | pag2 eof 13
Analytical Calibration and Equipment Control

3.5 The Analytical Development Manager is responsible for proactively ensuring
equipment used for testing is in working condition for its intended use and for
maintaining records of equipment maintenance.

3.6 The Analytical Development Manager is responsible for ensuring this procedure is

accurate, understood, and implemented effectively. This procedure may not be changed
without the authorization of the Analytical Development Manager.

4.0 Definitions

4.1 Analytical Instrumentation — instruments/machines used for the procurement of data

used in the release of a batch

4.2 QC — quality control

4.3 Calibration — set of operations which establishes, under specified conditions, the
relationship between values indicated by a measuring instrument or measuring system
and the corresponding standard or known values

4.4 GMP — Good Manufacturing Practices; a system for ensuring that products are

consistently produced and controlled according to quality standards

5.0 References

5.1 C-502, SOP, Record Storage, Retention, and Destruction

5.2 D-117, SOP, Laboratory Purchases and Receiving

5.3 D-602, SOP, Labelling and Expiration Dating of Laboratory Chemicals

5.4 G-102, SOP, Equipment Profiles

she, G-201, SOP, Calibration Program

5.6 QS-108, SOP, Corrective and Preventative Action.

6.0 Procedure

6.1 Prior to use, calibrated or verified equipment, standards and/or reagents are checked to
ensure they are within their valid period of calibration or expiration status as

appropriate. No equipment is used if its calibration has expired or if its calibration
status cannot be determined. No standard or reagent is used if its expiration date is past
due.

[SOP

Standard Op . e rating 2 Procedure S G O - P 2 0 N 8 o | Re 0 v Page 3 of 13
Analytical Calibration and Equipment Control

6.2 All personnel who use calibrated or verified instruments are trained (or have established
experience when hired) in the selection and use of such instruments so they understand
the required measurement accuracy and use measuring equipment that is capable of the
required precision. Test Methods and internal test procedures identify the

measurements required for each test, including the tolerances associated with the
required measurements. Test Methods identify the equipment required, measurement
equipment required, and methods used to perform Lab testing.

6.3 Personnel do not adjust, nor attempt to calibrate any instruments subject to calibration.

Equipment suspected of needing calibration is submitted to, or brought to the attention
of, the Analytical Development Manager.

6.4 Calibrated or verified instruments are used, handled, stored, and transported in such a
way as to prevent damage, contamination, or deterioration and to protect their integrity.
Where possible and applicable, such instruments are safeguarded from adjustments that

would invalidate the calibration setting.

6.5 General equipment used to perform testing is maintained in good working order to
ensure proper performance. Prior to performing testing, the equipment is verified to
ensure it 1s working, as necessary.

7.0 Procedure

7.1 Process Inputs

7.1.1. Entries in to the Calibration and Equipment Control process include, but are not
limited to:

7.1.1.1 Laboratory activities which require calibrated or verified equipment
to satisfy requirements of established test standards.

7.1.1.2 Laboratory activities which require functional equipment to perform

calibration services.

7.1.1.3 Established test standards which define required equipment
specifications, accuracy, and performance.

7.2 Laboratory Environmental Conditions

7.2.1. Where established calibration methods require monitoring and control of
environmental conditions, these conditions including but not limited to

temperature are measured using calibrated equipment such as a thermocouple
meter, calibrated mercury thermometer, or other equipment traceable to
appropriate national or international units of measure which apply to the

[SOP

Standard Operating Procedure SOP No | Rev Pave 4 of 13
Analytical Calibration and Equipment Control G-208 0

environmental condition which must be monitored and controlled. The
calibrated equipment used for these measurements are included in the
calibration control process described in this procedure.

7.2.2 If environmental conditions stray from the required specification, appropriate

action is taken. The events which caused environmental conditions to stray is
recorded and evaluated, and appropriate corrective action taken as described in
the Nonconformity and Corrective Action procedure. Corrective actions taken
will consider calibrations being performed when the environmental conditions
strayed and the duration of the event which caused the environmental conditions

to stray. If investigation of the event indicates the events could recur, actions
are taken to prevent recurrence.

7.3. Acquisition of Equipment

7.3.1 The Laboratory Management and/or the Analytical Development Manager
ensures the Lab is furnished with all items of measurement and test equipment

required for the correct performance of testing services (including
environmental monitoring, preparation of test items, processing, and analysis of
test data). No testing is performed outside of the Lab’s permanent control.

7.3.2 The Analytical Development Manager will act as described in the Purchasing
and Receiving procedure (D-117) to acquire measuring and other equipment

required to perform calibration services. The following hierarchy of order is
used while selecting equipment:

7.3.2.1 Equipment which will satisfy or is specified in requirements of the
established calibration method,

7.3.2.2. Equipment with accuracies matching similar equipment,

7.3.2.3. Equipment which achieves performance of stated tolerances as

indicated by the equipment manufacturer or calibration certificate.

7.3.3. If equipment is purchased as calibrated or verified, the Laboratory Management
or Analytical Development Manager will review the purchasing information
communicated to the supplier to ensure that traceability requirements to national
or international standards, to make sure that calibration and/or verification

requirements and certificate requirements are included, and that the
manufacturer is accredited to ISO 17025. If the manufacturer is not accredited
to ISO 17025 or is not an allowable exclusion for accreditation, the equipment
must be calibrated by an accredited calibration service provider prior to use.

[SOP

Standard Operating Procedure SOP No | Rev Santer ts
Analytical Calibration and Equipment Control a=205 0 mer

7.3.3.1 If the equipment is purchased as not calibrated (only certified for
accuracy or inspection), the equipment is calibrated or verified, as
applicable, in-house or by an accredited calibration service provider
prior to use.

7.3.4 Upon receipt of newly purchased equipment and prior to initial use, the
equipment, and their accompanying certifications (as appropriate) are sent to the
Analytical Development Manager. The equipment is evaluated to determine it
meets specified requirements for the function it will perform, and the condition
of the equipment is assessed to determine if it is in proper working order prior to

being put into service. The Analytical Development Manager will add the new
equipment to Calibration Database. Equipment will then be moved to the
appropriate area for storage or use.

7.3.5. Instruments used during accredited testing are typically identified by a
calibration label attached to the equipment or, where appropriate, on the

equipment case. Calibration labels show the valid period of calibration (the date
calibrated and date due), the service provider who performed the most recent
calibration, and the equipment’s unique serial number. If labels are not used
(e.g., not practical), the equipment’s calibration status and information are

available according to equipment’s Calibration Records and according to their
serial numbers.

7.4 | Equipment Calibration

7.4.1. Only calibrated or verified equipment is used in testing. Any software and
comparative references used during accredited testing will also be periodically
confirmed to ensure continuing suitability and effectiveness. Software used

during accredited testing is also identified in the Software Validation Log and
confirmed using appropriate methods such as data output reviews, known failure
testing, etc. In lieu of this, Ion relies on the IQ/OQ performed by the
manufacturer.

7.4.2 The Lab maintains metrological traceability of its measurement results by means

of a documented unbroken chain of calibrations, each contributing to the
measurement uncertainty, and linked to an appropriate reference. The
calibration process described in this procedure will maintain metrological
traceability and provide records documenting the unbroken chain of calibrations.
Measuring equipment is calibrated based on the conditions listed below.

Equipment subject to these requirements are identified in the Calibration
Database.

[SOP

Standard Operating Procedure SOP No | Rev ees
Analytical Calibration and Equipment Control G-208 0 ape 0

7.4.2.1 The measurement accuracy or measurement uncertainty of
equipment will affect the validity of the reported laboratory results,

7.4.2.2 When calibration of the equipment is required to establish
metrological traceability of the reported calibration services results,

7.4.2.3. Test and measurement equipment is used to control critical
calibration functions or acquire calibration data,

7.4.2.4 Test and measurement equipment is used to acquire calibration data.

7.4.3 The various Calibration Database’s spreadsheets include the following
worksheets as appropriate for their intended use:

7.4.3.1 Change History — records of changes to worksheets.

7.4.3.2 Calibration or Verification — identification of equipment requiring
calibration or verification and calibration/verification information.

7.4.3.3 Equipment Maintenance — identification of equipment designated as
calibration not required.

7.4.4 The worksheets in the Calibration Database establish the control features
necessary to control, calibrate or verify, and maintain monitoring and

measurement equipment. Each database includes instrument type (including
software or firmware version) or standard, unique identification, manufacturer’s
name, location, and frequency of checks. Associated certificates of calibration
from external calibration services identify the check method and acceptance

criteria.

7.4.5 The Lab Management or Analytical Development personnel selects providers of
calibration services according to the Purchasing and Receiving procedure, using
the same process described for acquiring measuring and other equipment
required to perform laboratory operations (see above). All providers of

calibration services are required to provide documented evidence (typically in
the form of a calibration certificate) of traceability to national or international
standards for measurement for each calibration performed.

7.4.6 Prior to selecting a calibration service provider, Lab management or the
Analytical Development Manager will ensure the provider maintains a current
accreditation to ISO 17025 and has the capability to perform calibrations

traceable to the U.S. National Institute of Standards and Technology and the
International System of Units (SI), or other national metrology institution.

[SOP

Standard Operating Procedure SOP No | Rev Seen) ef Es
Analytical Calibration and Equipment Control G-208 0 5

7.4.6.1 If the calibration service provider does not maintain a current
accreditation to ISO 17025, approval by the Lab’s accreditation body
is required prior to initial use.

7.4.7 All equipment requiring calibration undergoes an initial calibration before being

put into service unless it was purchased as calibrated by an accredited
calibration service and the equipment is in their scope of accreditation.
Thereafter, calibration intervals are determined at a frequency described in the
equipment profile that was created according to G-102.

7.4.8 The Analytical Development Manager reviews the Calibration Database on a

routine basis to determine equipment due for calibration. When the Calibration
Database indicates calibration is required, arrangements are made for calibration
to be performed by the selected calibration service provider. If equipment is
shipped off site for calibration, actions are taken to protect the equipment from
damage while in transit.

7.4.9 When calibration or verification has been completed, the calibration service
provider will apply a calibration label to the instrument or standard (or its case)
which indicates the date of calibration and the next calibration due date. If it is
not feasible to apply a calibration label to the device or its case, identification of
calibration status is achieved through other means in the vicinity of the

equipment to identify its calibration status.

7.4.10 The calibration service provider will provide a certificate of calibration (or
equivalent), indicating the results of the calibration or verification. The
Analytical Development Manager will review each certificate to ensure the
following data is present (at a minimum) to ensure compliance with ISO 17025:

7.4.10.1. A valid accreditation body endorsement for the calibrations
performed in the form of an accreditation body logo. If an
accreditation body logo is not present on the calibration certificate,
the calibration certificate must contain the following four elements

on the first page of the calibration certificate:

e A statement that the calibration meets requirements of ISO
17025,

e The name of the accreditation body which accredited the

calibration laboratory,

e Reference to the calibration laboratory’s accreditation certificate
number, and

[SOP

Standard Operating Procedure SOP No | Rev
G-208 0 Page 8 of 13
Analytical Calibration and Equipment Control

e A statement that the calibration is within the calibration
laboratory’s scope of accreditation.

7.4.10.2 Title (e.g., “Calibration Certificate”);

7.4.10.3 Unique identification of the calibration certificate (such as the serial
number);

7.4.10.4 The name and address of the laboratory, and the location where the
calibrations were carried out (if different from the address of the
laboratory);

7.4.10.5 The name and address of the Ion Labs;

7.4.10.6 A description of the condition of and unambiguous identification of
the equipment calibrated;

7.4.10.7 The date of receipt of the equipment (if this is critical to the validity
and application of the results);

7.4.10.8 The date(s) of performance of the calibration;

7.4.10.9 Reference to the sampling plan and procedures used by the

calibration laboratory or other bodies (if these are relevant to the
validity or application of the results);

7.4.10.10 Identification of the method used:

7.4.10.11 Evidence that the measurements are traceable to national standards,

7.4.10.12 Acceptance criteria;

7.4.10.13 The uncertainty of measurement and/or a statement of compliance
with an identified metrological specification or clauses;

7.4.10.14 Environmental conditions under which the calibrations were made
that have an influence on the measurement results;

7.4.10.15 The calibration results, with the units of measurement where
appropriate;

7.4.10.16 Description of adjustments made if applicable;

74.10.17 The name(s), functions(s) and _ signature(s) or equivalent
identification of person(s) authorizing the calibration certificate;

[SOP

Standard Operating Procedure SOP No | Rev
G-208 0 Page 9 of 13
Analytical Calibration and Equipment Control

7.4.10.18 Where relevant, a statement to the effect that the results relate only to
the items calibrated;

7.4.10.19 Each page of supporting data supplied with the calibration certificate
requires identification to ensure the page is recognized as a part of

the calibration certificate package;

7.4.10.20 A clearly identified end of the calibration certificate package must be
provided.

7.4.11 If the results of calibration as provided by the calibration service providers or
reference material data includes reference values or correction factors, the Lab

will ensure that spreadsheets used to present data are encoded with the proper
formula to account for the correction factor. Any spreadsheet or software used
for this will be validated and records will be maintained.

7.4.12 The Analytical Development Manager or Laboratory Management will ensure
the device’s calibration label has been updated appropriately before making the

device available for use. The Analytical Development Manager will update the
calibration record and equipment status in the Calibration Database indicating
the results of the calibration service.

7.4.13 The Analytical Development Manager resolves any discrepancies discovered
during review of the certificate or the calibration label by contacting the

calibration service provider, requesting corrective action as appropriate based on
the nature of the discrepancy. If the calibration certificate does not include all
the information required above, the calibration service provider must provide a
valid reason for not including it.

7.4.14 Where equipment performance includes correction factors or reference values,

this data is updated and implemented as appropriate based on the outcome of
calibration activities to ensure specified requirements are met.

7.5 Problems with Equipment

7.5.1 If calibrated equipment is dropped, damaged, or suspected of being out of
calibration, Lab Management or the Analytical Development Manager is
notified. If the Analytical Development Manager or Lab Management finds

action is required to ensure the equipment meets requirements, the equipment is
dispositioned using one or more of the following options:

7.5.1.1 Recalibration or verification

7.5.1.2 Withdrawing the equipment from use

[SOP

Standard Operating Procedure SOP No | Rev
G-208 0 Page 10 of 13
Analytical Calibration and Equipment Control

7.5.1.3. Changing the frequency of calibration or verification

7.5.1.4 Limiting the calibrated range or use of the equipment (the equipment
is Clearly identified as having a limited calibration with the limitation
stated on the equipment and in the Calibration Database)

7.5.2 When calibrated equipment is found to be out of calibration, the Analytical
Development Manager will assess the validity of previous laboratory activities
and the results of previous calibration services performed while the accuracy
and precision of the device was in doubt. The Analytical Development Manager
will investigate the impact of the potentially errant measurements on laboratory

results. The results of the impact investigation are recorded in records associated
with the equipment (typically in the Calibration Database).

7.5.2.1 A corrective action to track resolution of the issue may be initiated,
as appropriate.

7.5.2.2 When the assessment indicates the accuracy of previous calibration

results may have been compromised by calibrated equipment that did
not achieve required measurement accuracy and operate with
acceptable measurement uncertainty, the Analytical Development
Manager or Lab Management will notify affected customers as
appropriate in accordance with the nonconforming work routine

described in the Nonconformity and Corrective Action procedure
QS-108. Records of notification to customer(s) is maintained along
with the records described in the Nonconformity and Corrective
Action procedure.

7.6 Frequencies and Review for Calibrated Equipment

7.6.1 The Analytical Development Manager reviews the results of each calibration to
maintain confidence in the calibration program and calibration status of
equipment. This review will consider the amount of usage for the equipment as
well as the results of calibration activities. Where a change to the calibration
frequency is appropriate, the Analytical Development Manager will edit the

calibration frequency indicated in the Calibration Database. A justification for
the change, the date of the change and the person authorizing the change
(typically the Analytical Development Manager) will also be recorded in the
Calibration Database.

7.6.2 Calibration intervals may be shortened or extended based on the following
conditions:

[SOP

7.6.2.1 Where sufficient calibration data exists to statistically establish a
trend assuring good measurement results for a period longer than the
current period.

7.6.2.2 Limited or extensive use may influence the amount of time between

calibrations or verifications, as appropriate.

7.6.2.3 Risk of possible out-of-tolerance drift may also be used as a
consideration in adjusting the calibration frequency.

7.6.2.4 Equipment that is delicate, subject to frequent usage or severe
conditions (1.e., shock and vibration, excessive heat, or humidity, or

transported) is assigned calibration intervals shorter than would be
assigned if the equipment were not delicate or subject to frequent use
or severe conditions.

7.6.2.5 Infrequently used test equipment (e.g., used once or twice between
calibration cycles) may be assigned the status of “Calibrate Before

Use” instead of a periodic calibration.

7.6.3 If intermediate checks are necessary to maintain confidence in the calibration
status of the equipment, the method and required check frequency is identified
in the Calibration Database. Lab Management or Lab Technician will conduct
such checks when appropriate based on stated requirements in the Calibration

Database. Records of intermediate checks are included in calibration records. If
the results indicate an out of tolerance condition exists, an impact investigation
is conducted in accordance with the process described above.

7.7 Equipment Maintenance (for equipment not subject to calibration)

7.7.1 Lab Management or the Analytical Development Manager will review the

Calibration Database on a routine basis to determine equipment due for
maintenance. When the Calibration Database indicates maintenance is required,
arrangements are made for maintenance to be performed.

7.7.2 The Equipment Maintenance worksheet in the Calibration Database establishes
the control necessary to monitor equipment requiring routine maintenance
and/or qualification. The worksheet identifies completed activities, frequency,

and due dates.

7.7.3. Scheduled maintenance and operational checks are performed on equipment
required for the correct performance of laboratory activities and that can
influence calibration results. Required maintenance activities and frequencies

[SOP

Standard Operating Procedure SOP No | Rev
G-208 0 Page 12 of 13
Analytical Calibration and Equipment Control

are defined in the Calibration Database. The following is considered when
determining maintenance frequency.

7.7.3.1 Manufacturer’s recommendation;

se Amount of use;

7.7.3.3 Risk of equipment failure;

7.7.3.4 Lead time required for repair or replacement of equipment or
components.

7.7.4 When equipment breaks down or fails, it is repaired or replaced at the discretion
of Lab Management or the Analytical Development Manager. Any repairs or
new equipment is ordered and fulfilled according to the Purchasing and

Receiving procedure. Records of repairs are maintained in the equipment
record.

7.7.5 Equipment that has been subjected to overloading or mishandling, gives suspect
results, or has been shown to be defective or outside specified limits, is taken
out of service. Such equipment is isolated and/or clearly labeled as being out of

service to prevent its use until it has been repaired and has been demonstrated to
perform correctly.

7.7.6 Where suspect equipment has been used, Lab Management or the Analytical
Development Manager will examine the effect of the defect or departure from
specified limits on previous results. Lab Management or the Analytical

Development Manager will maintain a record of the investigation in the
associated equipment records. Lab Management or the Analytical Development
Manager will notify customers as appropriate if previous results have been
impacted in accordance with the nonconforming work routine described in the

Nonconformity and Corrective Action procedure QS-108. Records of
notification to customer(s) are maintained along with the records described in
the Nonconformity and Corrective Action procedure.

7.7.7 Maintenance is performed by external services or by internal personnel as
determined by Laboratory Management or the Analytical Development
Manager. External service providers will conduct maintenance activities as

required by contracts or purchasing information provided to the external
provider, referencing maintenance or operations manuals, as appropriate.
Maintenance performed by internal personnel is conducted according to general
maintenance practices and/or in accordance with equipment manufacturer’s

[SOP

Standard Operating Procedure SOP No | Rev
G-208 0 Page 13 of 13
Analytical Calibration and Equipment Control

recommendation. Records of maintenance activities are maintained as described
in C-502 Record Storage, Retention, and Destruction.

8.0 Process Outputs

8.1 Outputs from the Calibration and Equipment Control process include, but are not
limited to:

8.1.1 Operational, monitoring, and measuring equipment that performs as required
and is calibrated to appropriate standards.

8.1.2 Non-measurement equipment that performs as required.

8.1.3 Records of calibration and maintenance.

9.0 Revision History

| Rev | Date | Description of Changes | CCR # | By |
|-----|----------|------------------------|-------|----|
| 0 | 11/10/21 | New procedure. N/A J. Maignan | - | - |