Developing and

Implementing Calibration
Programs

Andy Ferrell
PCI CEO & President

March 19, 2013

Pennsylvania Convention Center
Philadelphia, PA USA
 Wm. Andy Ferrell - Bio
• Bachelors and Masters degrees from East Carolina University
• Engineer with big pharma companies from 1989 to 1996
• Speaking on topics such as:
– Smart Asset Management
– Emerging Trends in Calibration Compliance
– Predictive Maintenance and Calibration Programs: Improving Operations
• Founded PCI in 1996
• PCI is 110 person firm. Headquartered in RTP, NC with 5 field offices and
national consulting & technical service coverage
• PCI’s Technical Services: delivering calibration, maintenance, and repair
services for both manufacturing and laboratory equipment
• PCI’s Consulting Services: building calibration & maintenance programs
including developing business workflows and policies, implementing
software systems, FDA remediation plan development & execution. We
development world class maintenance & calibration programs
 Introductions:
Who are you?

 Name
 Your role
 Company
 Industry
 Any Regulatory Concerns
 What are you seeking to get
from this workshop
 What we will cover
 Background Info …. Calibrations
 Basic Calibration Program Requirements
 What is a Calibration Program?
 Calibration Program Requirements
 Responsibilities of a Calibration Department
 Critical Elements of a Calibration Program
 Paperless: Changing Existing Cultures
 Benefits of going to a Paperless Program
 Calibration: Definition

A comparison of a measurement
“
standard (Calibration Standard) of
known accuracy with another
instrument of unknown accuracy to
detect, correlate, report, or eliminate
by adjustment any variation in the
accuracy of the item being compared.”
 Why Calibrate?

 Every day, industries throughout the

world perform a huge number of
measurements.

 The results of these measurements are

used to make decisions that could
affect people’s lives both personally and
in the workplace.
 Why Calibration?

Calibration is warranted based on good engineering

and business practices, and must adhere to
standards and regulations in the following ways:

Good engineering and business sense.

Instrumentation wears and settings drift, either
mechanically or because of environmental effects.

These conditions can have a negative effect on

instrumentation and can ultimately affect the
quality of a product.
 Without Calibrations

 All of us would pay more at the Gas station.

 Food would be weighed incorrectly.
 No more watching your favorite television
shows or listening to your favorite songs on the
radio, because due to calibration errors, the
frequency would be off enough that TV and
radios would be useless.
 Without Calibrations

 Ingredients in your prescription drugs could

cost more or even more important cause illness
or death.
 Because of incorrect calibrations, criminals could
be either not convicted or released on Bad
evidence.
 With Calibrations

 In pharmaceutical manufacturing and other

life science businesses, companies take
measurements throughout the various stages
of the product life cycle to ensure product
integrity.

 The certification and calibration of

instrumentation, combined with a robust
calibration management system, helps
achieve product integrity throughout all
production processes.
 The Calibration Train wreck

 In January 2005, during the annual Measurement Science

Conference (MSC) held in in Anaheim, California, one of the
participants from Germany explained to the group that he had been
a guest professor at an University in China. He explain that they
had an input of 8,000 students every year studying measurement
techniques. He went on to explain that the Chinese government has
increased the attendance to almost 12,000 students.

 Then the question came up, why doesn’t the United States or
Germany train in the field of metrology and calibration the way the
Chinese are doing?

 His answer was “ Because we haven’t had the train wreck yet.” We
haven’t had the train wreck where someone says, “ Calibration was
the Problem.” Where there was a great loss of life or limb, or many
businesses were effected.”
Regulations &
Guidances
 Regulations & Guidances

Regulations are Law.

 Example: the FDA has GMPs (Good
Manufacturing Practices) or CFR 21.
CFR 21 is Code of Federal Regulations for Food
and Drugs.
 Regulations are usually vague.
 Regulations & Guidances

Guidances are not Law. Usually published by

industry organizations.
 Much more specific than Regulations.
 Following Guidances does not provide 100%
certainty of zero observations or violations.
 Regulation & Guidance

Guidance Documents - Benchmarking

 ISPE GAMP Calibration Management (second edition)
 ISPE GAMP Validation of Lab Computerized Systems
 NCSLI RP-6 Calibration Control Systems
 ISO 17025 General Requirements for Calibration Labs
 ISO 98 Guide for Measurement Uncertainties
 Regulation & Guidance

IF we follow all the Guidelines, we are

guaranteed to be in compliance with the
Regulations.
True?
No, False
All Guidelines are fallible.
Industry Guidelines
 Industry Guidances
 NCSL International Recommended Practice RP–6
 ISO/IEC 17025:2005 specifies the general
requirements for the competence to carry out
tests and/or calibrations, including sampling
(proficiency testing)
 ANSI/NCSL Z540.3-2006
Requirements for the Calibration of Measuring
and Test Equipment
 The ISPE GAMP® Good Practice Guide:
Calibration Management
 Implementing a
Calibration Program
 Calibration Program Basics
 Calibration Policy and support Procedures (SOP)
 Calibration Records
 Qualified Personnel
 Calibration Training
 Calibration Labeling
 Calibration Intervals
 Calibration Logistics / Scheduling
 Define Out of Tolerance conditions or Non Conformance
 Process for Investigation of Non Conformances
 Adequacy of Calibration Standards
 Traceability (and Reverse Traceability)
 Analysis of Calibration Data
 Continuous Improvements (Audits)
Calibration Software
Requirements
 Implementing a
Calibration Software

1. Need to put together a team

2. Obtain Site/Management “Buy In”

3. Obtain appropriate funding

4. Put together timeline and resource allocation

 User Requirements (URS)

Calibration Software Considerations

 Implementation budget
 Platform supported
 Networked/ web based
 Number of assets to be managed
 Number of transactions annually
 Number of years required to be maintained
 User Requirements (URS)

 Ability to capture unique instrument

identification
 Ability to assign classification for each
instrument in the program
 Ability to capture the calibration test points
for each instrument
 Ability to schedule calibration services for
assigned specified intervals
 Ability to handle multiple test ranges
 Ability to record calibration data
 User Requirements (URS)

 Ability to run a matrix report showing, for a

specific time period and by various selection
criteria:
• Total # of scheduled calibrations
• Total # of active and total # of inactive
instruments at the beginning of time period
• Total # of scheduled calibrations [redundant, 1st
above]
• Total # of active and total # of inactive units as
they were at the end of time period
• Net change in total # of scheduled calibrations
 Calibration Program
Checks and Balances
 Both internal corporate compliance and third-party
regulatory bodies conduct Audits throughout the
pharmaceutical industry to ensure that
manufacturers are following their own procedures
and to see how they react to issues and deviations
to their processes.

 A robust Calibration Program is vital to ensure that

when similar audit points are challenged, it can be
demonstrated that systems, processes, and
procedures are in place to address potential
noncompliance issues.
Performance
Metrics
 Performance Metrics: Purpose
 Make strategic objectives clear, in order to focus
and bring together the total organization
 Tie the core business processes to the objectives
 Focus on critical success factors for each of the
processes, recognizing there will be variables
 Track performance trends and highlight progress
and potential problems
 Identify possible solutions to the problems
 Performance Metrics

What Gets Measured Gets Done.

What Gets Measured, Improves!!!

 Performance Metrics: Example
% Calibrations performed: Laboratory Instruments

Calibrations Scheduled % calibrations performed

500 100.0%
450 98.0%
400 96.0%
350 94.0%
300 92.0%
250 90.0%
200 88.0%
150 86.0%
100 84.0%
50 82.0%
0 80.0%
Jan-04 Feb-04 Mar-04 Apr-04 May-04 Jun-04 Jul-04 Aug-04 Sep-04 Oct-04
Auditing
Developing & Implementing Calibration
Programs:

The 4 Most
Critical Elements
 The 4 Most Critical
Elements of Calibration Programs

• Classification
• Intervals
• Ranges
• Limits
 Classification, Intervals, Ranges,
and Limits
 An instrument/device is classified based on its potential
to affect a product or products.

 This classification is defined and documented in a

paperless system using such terms as “critical,” “non-
critical,” or “reference only.” Characteristically, where
process parameters are monitored, controlled, or
recorded, and are used to determine product quality,
the associated instruments would warrant a critical
classification.

 Most instruments associated with noncritical and utility

classifications are used to provide indications of general
equipment conditions and for troubleshooting.
 Classification, Intervals, Ranges,
and Limits

 Interval or service frequencies or schedule.

 For regulated environments, it is typical to assign
Intervals of weekly, monthly, quarterly, semi annual,
and annual.
 Bi-annual are used but are uncommon.
 Daily are typically not used. Calibration Before Use
is typically assigned instead of daily intervals.
 Interval Assignment
Considerations
• Does a measured and controlled parameter
on product have a direct effect on product
safety or quality (e.g., sterility)?

• What is the instrument’s (OEM) stated

reliability and accuracy?

• What is the time from product manufacture

to use?
If this time is relatively short, adulterated
product could be distributed & used if
improper intervals are set.
 Classification, Intervals, Ranges,
and Limits

o Instrument Design Range

The design range or maximum range of operability of the
instrument, as specified by the manufacturer. This must be wide
enough to ensure that the instrument is capable of reliably
operating across the entire qualified range for the equipment.

o Process Operating Range

Specified range within which the process must operate.

o Instrument Calibration Range

The calibration range must be, at a minimum, equal to the
qualification range. A wider calibration range, however, can be
useful for non-linear instruments or whenever the qualified range
is too small to prove linearity of the instrument.
 Classification, Intervals, Ranges,
and Limits

Considerations
• Given to the criticality (or classification) of
the instrument
• Given to the environment in which the
instrument is used
• Given to the users
• Will the instrument be used for the same
test consistently
 Classification, Intervals, Ranges,
and Limits (tolerance)

An Example:

 Instrument’s Design Range

0 deg C to 200 deg C

 Operating Range
20 deg C to 80 deg C

 Instrument Calibration Range

10 deg C to 100 deg C
 Classification, Intervals, Ranges,
and Limits (tolerance)

 The calibration tolerance is the maximum allowable

deviation of an instrument from true value before
there is an effect on product and is utilized for critical
instruments/devices. This predetermined tolerance is
used as an out-of-tolerance investigation trigger.

 The Manufacturer’s Accuracy Specifications should not

be used as the Calibration Tolerance Limit
 Classification, Intervals, Ranges,
and Limits (tolerance)

An Example:

 Instrument’s (OEM) Design Accuracy

+/-1.0 deg C

 Your Adjustment Limit

+/- 1.5 deg C

 Your Calibration Tolerance

+/- 2.0 deg C
Instrument Tolerance Relationship

.
Calibration Tolerances
 Classification, Intervals, Ranges,
and Limits (tolerance)

General Rule

If an investigation of an Out of Tolerances does

not result in a product rework or recall, the
Process Tolerance should be set to avoid doing
the same investigation if the instrument fails
calibration by a similar or less value
 The Rule of Thumb for
Setting Calibration Tolerances

 All instruments drift. No exceptions.

 Therefore, Never use the Manufacturer’s

Specifications for Accuracy as the Calibration
Tolerance!

 Rule of Thumb: double the OEM’s stated

accuracy for your calibration tolerance. If
that doesn’t meet your needs, purchase
another instrument.
Break
 Your Bonus
Jean Piaget was a scientist who in the early 1900's studied the
tendency to focus attention on only one characteristic of shape. In
particular, he studied the human inability to distinguish identical
volumes in different sized containers.

Piaget studied the inability of small children to understand that

cylinders with different aspect ratios could have the same
volume. Small children have difficulty conceiving the shift
in volume from one dimension (say the width of a glass) to another
dimension (say the height of a glass). They have difficulty visualizing
that there is no more liquid in a tall, slender glass than in the shorter,
wider glass. He showed that for certain individuals, this tendency
could extend into adulthood.
This is illustrated in the following Figure:
 The Visual Measure
The tendency is to believe that even though the two glasses have
the same volume, the tall, slender glass has more volume because
the height of the liquid is greater.

This fact explains why studies show that mixed drinks at bars that
use short, wide glasses are typically stronger then the same drink
at bars that use tall, slender glasses. The height of a 1.5 oz. shot
of alcohol in the short, wide glass is not as high as the same 1.5
oz. shot in the tall, slender glass. When bartenders pour a shot in
a short, wide glass they have the tendency to think that since
the liquid level is not very high they have mis-poured, and so add
a little more alcohol to the drink.

The moral of this study is always get your mixed drink from
bars that use short, wide glasses.
 The Beer Gauge

This misconception of relative volume is what leads us to

think that the relatively small top portion of a pint glass
could not contain such a large percentage of the total
volume. In fact, if beer is poured into a pint glass to
about 1/2 inch from the top, 13% of the beer is GONE.

A pour to about 1 inch from the top of the glass leaves

out 25% of the beer. This is illustrated below, where the
"Beer Gauge" is used to indicate the amount of beer
missing from the pint glass.
 Your Bonus

The PCI Logo’d BEER GAUGE!

Use Responsibly
 Paperless Calibration
Programs

Why Paperless Calibration?

 Why Paperless Calibration?
 Digitizing and automating calibration has
decreased downtime and improved efficiency
 Through better calibration testing and setting
of tolerances, firms will find a great cost
reductions in operations and fewer Out of
Tolerance investigations.
 Understand and accept that in the world of
Calibration, everything around us is changing, it
doesn’t matter if it’s the calibration procedure,
calibration records, our calibration standards,
instrument owners, or instrument use.
Investigation Activity
Features of a Paperless
Calibration Program
 Features of a Paperless
Calibration System
Investment in a paperless system is easy to justify; a few of the
basic advantages include:
• Fewer errors occur because planners, managers, and
technicians are reliably notified of pending calibration
events.
• Calibration obligations cannot be forgotten or overlooked.
• Technicians can no longer perform a calibration without
properly documenting.
• The use of unsuitable or out-of-calibration test standards is
no longer an option.
• A paperless system ensures that everyone who needs to
know of a specific event is notified in a timely fashion
Example: if a device is found out of tolerance or if a
calibration failure occurs, notifications are automated.
 Features of a Paperless
Calibration System

• Worker training and qualifications

• Facility documentation
• Work flow diagrams
• Sample details
• Work requested
• Work performed (procedures, calibrations, etc.)
• Results, reports, graphs, etc.
 Features of a Paperless
Calibration System

 Records are auditable

 Records are accessible (by others, and from
year to year)
 Provides a framework to implement/prove
work controls
 Automated report generation
 Records tend to be more complete than
notebook entries. That is, all supporting
materials (spreadsheets, plots, models,
figures, references, protocol, etc.) are
attached, too
 Overall Program
Compliance Improvement

 Can be set up to ensure Technicians do not leave

instrumentation out of compliance or hard document
GMP issues via the business rules of the application and
real time warnings, alerts, and work order application
rules.

 All Measure Data Test Points can be loaded and

Technicians must follow decision data of Calibration
Tolerance limits,

 Adjustment Limits and Process Limits. Each of these can

have a business rule that correspond to an application of
the system electronically notifying the designated party
via email, and shows pending days, hours, etc of work
pending.
 Culture Challenges

• Anything new is initially resisted: the

historical notebook and notebook pages
are gone.

• Scientists may hate paper, but experience

separation-anxiety in its absence.

• Your notebook is not your private space

anymore: viewed by all, pre-signature.

• E-signature compliance is easier to

monitor, but resented.
 Culture Challenges

•Data and results may be stored on separate

computers
•Handwritten notes on paper
•Generated data files are stored on a network
server (Linux based, dedicated to and physically
located in my lab, backed up corporately) that has
terabytes of storage available, and room to expand
•Experimental results are communicated to
customers via memos, printouts, email, etc.
Break Anyone?
Paperless Program Considerations
This is a PROJECT.
 Paperless Benefits: Business Areas/End Users
Engineering Department QC Laboratories
Manufacturing Departments R&D Laboratories

 Identification and specification of business area

and end user needs
 Identification and specification of the intended
uses of the system
 Review and approval of the User Requirements
specification document
 Paperless Program Considerations
Realistic Expectations

 Few Companies Achieve 100% Paperless

 We see a Continuum from 0 to 100%
“Paperless”
It doesn’t have to be all or nothing
 Corporate Attitudes to support it vary
greatly
 Investment rates vary
Benefits of a Paperless Calibration System
 Facilitating regulatory compliance
 Completeness of records
 Ease of searching records
 Managing who has access to information
 Review and approvals
- Time savings when generating reports
- When recreating the past
- When archiving data
 Cost savings (by-product of the previous
benefits listed)
Benefits of a Paperless Calibration System

 Saves time
 Reduce human error
 Full Standards traceability
 Automatic tolerance calculations
 Automatic flags and notifications for
calibration failure
Benefits of a Paperless Calibration System

 Productivity Improvement
 Print Calibration certificates with pre-
populated data
 Measurement Data Template reuse
 Reduce redundant data entry
 Reduces head count or maximizes resource
allocation
Benefits of a Paperless Calibration System
 Improved Compliance
– Automated reviews
– Less data errors
– Faster inspections and audits
– Lowers costs related to Paper, filing,
storage
Benefits of a Paperless Calibration System

 Management Of Work
 Work Scheduling
 Work Assignment
 Calibration Planning
 SOP
 Measurement Data Template
 Standards
Benefits of a Paperless Calibration System
(Recap)
 History Record
 Permanent record
 Reviews & Approvals
 Consistent Service Delivery
 Auto Notifications
 Audit Trail
 Making It Happen
Assess Infrastructure
 Wireless
 Mobile Computing
 Laptops, tablets, netbooks
 PDA’s, cell phones, etc.
 Network Drops
 Cellular cards
 The ‘Take Away’
 A solid Calibration Program is a must in
business and science today
 A paperless Calibration Program is a
commitment from the top
 The benefits of a paperless Calibration
Program far outweigh the cost IF this
approach is right for your organization
 Developing & Implementing
Calibration Programs

Q&A
 THANK YOU

Wm. Andy Ferrell

PCI, LLC
'Providing Instrument & Equipment
Compliance Solutions Since 1996'

8100 Brownleigh Ste 100-A

Raleigh, NC 27617
aferrell@pci-llc.com
(919)781-7787 Office