GMP WAREHOUSE MAPPING - STEP-BY-STEP GUIDELINES FOR VALIDATING LIFE SCIENCE STORAGE FACILITIES
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
GMP Warehouse Mapping / Step-by-Step Guidelines for Validating Life Science Storage Facilities
Good manufacturing practice (GMP) regulators in the United States, Canada, European Union, Japan, Australia, and China have sharpened their focus on warehouse storage and distribution practices. Driving this trend is a shift in regulatory thinking from quality-by-test to quality-by-design systems with emphasis on level of risk to product quality and patient safety. Other drivers include greater demand for storage facilities due to globalization of manufacturing, increase in temperature-sensitive biopharmaceuticals, and changes in technology. Regulators in these countries citations of GMPs.) This guide, require “mapping” the temperature intended for use by any organization and relative humidity profile of involved in the storage and distribution warehouses for environmentally of products sensitive to temperature sensitive life science products. This and humidity in a GMP-compliant step-by-step guide describes how to environment, draws on Vaisala’s map a warehouse to comply with extensive customer experience internationally recognized GMPs, throughout North America and Europe. including many that have been Indeed, Vaisala’s environmental and published or revised recently. (See industrial measuring and monitoring Regulations and Guidance at the products are used in more than end of this paper for more detailed 140 countries. 2
Step by Step – Good Practice Warehouse
Mapping
Vaisala recommends a nine-point Step 1: Create a The master validation plan should –
process for successful mapping Validation Plan • State the validation objectives.
of a warehouse or other regulated
The validation plan, or validation
storage space: • Identify roles and responsibilities
master plan, is the document
of quality, metrology, and other
used to specify the company’s
working groups in the process.
commitments and decisions about
1. Create a validation plan
qualifying every aspect of the • Identify validation activities,
2. Identify areas at risk facility, equipment, and people including processes, equipment,
to maintain a GMP-compliant and space.
3. Develop protocol information
environment. The plan should
• Develop documentation and
4. Determine sensor distribution take a risk-based approach, with
procedures, including the
a rationale based on science
5. Select suitable technology company’s response should
and verifiable measurements.
a temperature or humidity
6. Set up mapping equipment The plan should focus on where
excursion occur.
environmentally sensitive products
7. Conduct test and review data
and materials will be stored and • Define a validation schedule.
8. Make modifications whether environmental controls
• Specify the management approval
can meet specified storage
9. Document and schedule process, especially for adverse
requirements.
mapping tests events such as out-of-temperature
The plan is also a starting point for deviations.
regulators to evaluate the rationale
These nine steps will help you • Identify change-control protocols
for the company’s goals and
design and execute a successful so it’s clear when changes such as
methods.
mapping plan. They will ensure maintenance, new construction,
that you take into consideration and reconfiguration of racks
the most important elements of require revalidation.
validation, especially Regulatory Note: GMPs require
understanding maintaining temperature
where and humidity
temperature within storage
and humidity recommendations
pose risks printed on
to product product labels
quality. or provided by
Following raw-material
these steps suppliers.
will go a long These
way in recommendations
demonstrating are derived from
to a regulatory known chemical
inspector that your properties and
company is stability testing.
GMP compliant.
3
Step 2: Identify Areas • Independent energy sources, such Step 3: Develop Protocol
at Risk as space heaters, air conditioners, Information
and fans, which create warm or
To map a warehouse or other Once you’ve identified areas of risk,
cold pockets.
storage space, you first must develop a protocol for the mapping
identify areas where product • Layout of racks, shelves, and test that describes the following,
quality may be at risk because pallets, which obstruct airflow. with justifications for each decision:
of unacceptable variations in
• Location of HVAC control sensors. • Types of data to be generated – for
temperature and humidity. Many
For example, a thermostat located example, temperature, relative
factors affect the control or
near a source of heat or cold may humidity, and measurement
variability of your space. (Because
cause the temperature of the intervals. Five-minute intervals
relative humidity is dependent
space to fluctuate excessively. offer more data to evaluate trends
on temperature, variations in
and modify the warehouse setting
temperature will affect humidity • Locations near sources of heat or
(see Step 8). Once you are satisfied
as well.) Considering each of these cold, such as the roof and exterior
that temperature and humidity
factors will help you pinpoint risk: walls, windows, and loading dock.
are relatively stable, 15-minute
• Volume of space. A large • High-traffic areas where product intervals may be adequate for the
warehouse has different control or equipment is moved. final mapping.
burdens than a small storage
• Seasonal temperature changes or • Number of sensors to be used
area, with greater demands on the
unusual weather events. (see Step 4: Determine Sensor
HVAC system and the potential for
Distribution).
greater variations in temperature Regulatory Note: You can achieve
and humidity at various locations. GMP compliance through good • Map of sensor locations.
science and sound justification
• The capacity of diffusers or fans • Duration of study. Your rationale
of your approach to identifying
to adequately circulate air. and protocol may support a series
risk. The more considerations the
of tests, each lasting two days
• Temperature gradients between validation master plan addresses,
during normal operations and into
the cooler floor and warmer air the better your compliance rationale
a weekend. A different and equally
near the ceiling. is likely to be.
defensible protocol might specify
a single run over a two-week
period to account for a variety of
activities, such as opening loading
dock doors, in the warehouse.
• Calibration requirements of the
data loggers (specified by the
2 3 manufacturer).
5 • Acceptable range of variation over
time and across the space, which
will depend on the product stored.
7 8
1 4 • Acceptable limits for temperature
10 or relative humidity excursions.
12 13 • Reporting requirements.
6 9
Regulatory Note: Once you develop
a protocol, follow it consistently.
Loading 15 If the protocol changes, document
Door Door
the reasons.
11 14
Figure 1. The even distribution of 15 sensors is a typical pattern for three-
dimensional mapping of a small space.
4
Top
View
Figure 2. Sensors placed in the middle of racks reflect actual product temperatures. In this example, nine sensors are located
on each double rack in this warehouse measuring 30 meters by 30 meters by 15 meters.
Step 4: Determine Sensor dimensions with 15 sensors. The to set up. But convenience mustn’t
Distribution protocol should set bounds on the take precedence over effectiveness.
distance between sensors, such as Sensors must measure the
How many sensors will you need
no greater than 6 meters. conditions to which your products
to map a particular space? Where
or material are exposed.
will you put them? There are no In mapping a large warehouse,
formulas or pat answers. Sensor set sensors as far as 60 meters If you don’t have the sensors you
distribution must be adequate to apart, with additional sensors in need to map an entire warehouse
assess temperature uniformity. vulnerable areas affected by drafts in one test, you may choose to map
Good practice demands you use a from loading docks, heat or cold one section at a time. Mapping in
sufficient number to understand from external walls, solar heating sections takes longer, and you may
your environment, especially from windows, heat generated want to extend the mapping time for
problem areas where risk is from artificial lights, air circulation each section to compensate for the
greatest. from traffic or the HVAC system, uncertainty of mapping the space
temperature extremes in poorly piecemeal. To decide, weigh the
You’ll need to place sensors in
insulated areas, localized effects of equipment savings from a sectional
a uniform pattern in all three
space heaters and air conditioners, mapping approach against the
dimensions of your space – top to
and drafts from typical warehouse additional time needed to complete
bottom, left to right, front to back.
activity. Anticipate that airflow and the project.
Add additional sensors where you
temperature gradients may vary
suspect cool or warm areas may If high or low relative humidity
depending on whether shelves are
exist, as well as near the control can adversely affect product or
empty or stocked with product.
sensors and monitoring sensors. material quality, then you should
Taller racks will be subject to wider
Placement of temperature and map for relative humidity as well
temperature gradients, requiring
relative humidity sensors is a as temperature. There are two
more sensors top to bottom.
function of the considerations and approaches to determining the
risks you evaluated earlier in Step 2. You can mount sensors in open number and location of relative-
areas (outside of racks or aisles, for humidity sensors.
A walk-in chamber or small
example) where they are convenient
warehouse is often mapped in three
5
Such a strategy is not auditors to easily comprehend
without risks. without detailed explanation.
And relative-humidity excursions
Compared with temperature
(caused, for example, by fire
sensors, relative humidity sensors
sprinkler activation or other
are far more prone to to lose
unexpected moisture) will be
accuracy, or “drift,” over time. Drift
easier to identify and explain if you
may be caused by poor design, poor
measure relative humidity directly.
calibration, or contamination from
water-vapor saturation or chemical Regulatory Note: Understanding
vapors. A single errant reading environmental variability is
at recalibration time will call essential to successful mapping
attention to your decision to skimp outcomes and managing risk in a
on humidity sensors. Starting with GMP storage space.
fewer humidity sensors creates the
risk of nonconformance, because if Step 5: Select Suitable
one fails or is out of specification, Technology
that single sensor will represent
Use equipment designed for
a high percentage of your total
mapping. Sensors should be
humidity measurements. Deducing
integral with modern electronic
humidity compliance through
data loggers. Data loggers
temperature uniformity will require
measure, store, and record data
that a company employee with this
throughout the validation test.
specialized knowledge meet with
Software that accompanies the
the compliance inspector. Ideally,
data loggers is used to set up the
The first approach is to use your company should minimize
equipment and download data.
comparatively few humidity the number of contacts needed
Software should produce tabular
sensors distributed throughout during an inspection as a way to
and graphical reports that meet
the warehouse (as few as one for streamline the process and reduce
all requirements of 21 U.S. Code
every six temperature sensors) and the possibility of a misstatement.
of Federal Regulations Part 11 and
to rely on temperature uniformity If you’re concerned about relative comparable international standards,
to make the case that humidity is humidity, a more defensible mapping such as European Commission
also within bounds. This approach strategy is to track temperature Annex 11, and those contained in
relies on a history of temperature and humidity at all locations with European Union GMP Chapter 4.
mapping in different seasons with data loggers that record both (See Regulations and Guidance for
consistent results. With this history, measurements. It’s important to use details.)
a specialist with an understanding high-quality loggers that remain
of humidity measurement science When choosing data loggers, look
demonstrably accurate.
can effectively make the case to an for the following features:
auditor or inspector that humidity Mapping with integrated
• Minimum sources of error – that
measurements are not needed at all temperature and relative humidity
is, low measurement uncertainty.
data points. If you decide to follow sensors offers several advantages
this strategy and cut back on the over deducing humidity from • Sensitivity to small temperature
number of humidity sensors, it’s temperature. Mapping both changes. The more rapid the
crucial to place the few sensors temperature and humidity at response, the more closely the
you do use in areas with poor air all sensor locations provides a data point can be associated with
circulation, between HVAC fans or quantitative map of the entire the time of the measurement.
diffusers, and where temperature is storage space for inspectors and
most variable.
6
• Long-term stability, particularly Regulatory Note: GMPs require • Equipment has been validated.
for relative-humidity sensors, written procedures for calibrating, Installation qualification and
which are more prone than inspecting, and checking operation qualification
temperature sensors to drift. automated, mechanical, and (IQ/OQ) is typically provided by
Low-quality equipment may need electronic equipment (21 CFR the equipment supplier.
to be calibrated before and after 111.25). International standards
• Program access has been
every use. Stable, high-quality such as ISO/IEC 17025:2005 General
secured and authenticated.
data loggers demonstrated to be Requirements for the Competence of
Access privileges or permissions
accurate for 12 months or more Testing and Calibration Laboratories
restrict who is allowed to set
between calibrations will save are recognized best-practice
up the equipment and use the
time and produce better results by references for calibration.
application.
eliminating the need to calibrate
before and after every use. Step 6: Set Up Mapping • Software reads and records
• High accuracy in the range of use. Equipment hardware and firmware model,
version, and serial number.
Vaisala loggers, for example, are After you’ve identified likely risk
Software can identify each unique
accurate to 0.10°C (0.18°F) in an areas and determined sensor
piece of equipment.
operating range of -90 to 85°C distribution, it’s time to set up
(-130 to 185°F), and to 1 percent mapping equipment and conduct a • The warehouse area under test
relative humidity. mapping test of the storage space. has been precisely described.
The purpose of this initial test is
• Traceable calibration performed • Data logger locations are precisely
to determine where risky (that
within the measurement range – described. A pictorial map
is, variable) conditions exist, and
that is, calibrated with equipment helps ensure consistent sensor
where temperature and humidity
using an unbroken chain of placement in subsequent tests.
are uniform and suitable for product
comparisons to an internationally
storage. • Regular sample intervals have
recognized standard such as
been determined. Intervals
that of the National Institute of Work through the following
typically run between five and
Standards and Technology. The checklist, making sure each step is
15 minutes.
logger’s calibration certificate completed and documented:
should document all of the data • Test duration has been
• Equipment has been calibrated –
above. determined. All data loggers are
by whom, when, next calibration
set to begin and end at the same
• Clear, comprehensive, and date, and calibration confirms that
time.
accessible calibration records. the logger performs within the
limits of stated uncertainty. • Data loggers link to an audit
trail file for traceability. This
is an essential requirement to
show that documentation is
trustworthy.
• Data loggers have been positioned
in defined locations.
Regulatory Note: GMPs require
the use of calibrated equipment
and records to show maintenance
to acceptable standards. If you
gathered data in electronic form,
these records must meet regulations
for electronic records as defined in
21 CFR Part 11, in EC Annex 11, and
in European Union GMP Chapter 4.
(See Regulations and Guidance for
details.)
7Step 7: Conduct Test and Review Data
You’ll need to establish the • Raw data with times and dates. Overlay traces from each sensor
reporting information you’ll use to can be compiled onto a single
• Calculated values such as
evaluate the test. When the test is graph to provide a quick look at any
temperature minimum, maximum,
complete, software will read the temperature and relative-humidity
and average.
secure files from the data loggers, extremes. Preset lines, such as
show recorded data, perform • Graph of all sensors over the test acceptable minimum and maximum
calculations, and graph the results period. limits, can aid the analysis.
selected for the mapping report. The
• Instrument settings. The measured data become
test document will typically show
part of the secure record. This
the following information: • Calibration information.
record can help identify high-
• Date and time of the test. risk locations, especially where
problems occur sporadically. For
• Space for review and approval
example, a temperature spike may
signatures.
be linked to a time when loading
Figure 3. The mapping report can show high and low limits to quickly visualize acceptance criteria.
8doors were open. Such a variation Step 9: Document and
might indicate a risk from routine Schedule Mapping Tests
workplace activity or suggest the
After you adjust for environmental
need for a buffer zone.
variability in the warehouse, it’s
Regulatory Note: 21 CFR Part time to conduct and document a
11 and EC Annex 11 require that mapping test for approval.
computerized records be available,
How long should mapping last? Just
readable, reliable and secure. It’s
as with your initial mapping test,
better to present a summary graph
there’s no fast rule. Your rationale
with an easy-to-draw conclusion
and protocol may support a single
than a difficult-to-read report that
long test, or a series of shorter
may generate additional questions.
tests. Either way, it’s important to
measure the environment during
Step 8: Make a range of different work activities
Modifications in the warehouse, such as loading,
Use the results from the initial moving product, and periods such
test to identify locations where as weekends when little activity
the product would be exposed might occur.
to unacceptable extremes of
How often should you map a space? should provide enough flexibility
temperature or humidity. Then
Some protocols call for mapping to capture weather extremes. For
make adjustments—for example,
every three months while others example, depending on the climate
to the storage racks or HVAC
can justify mapping yearly or even in your area, your plan might
system—to correct this variation.
less frequently. The validation call for mapping when summer
Or simply decide where products
plan should anticipate the many temperatures exceed 30°C and
will not be stored. For example,
variables that can change storage winter temperatures fall below 0°C.
many warehouses have a
temperatures after completion
mezzanine level designated off- Regulatory Note: Maintaining useful
of a mapping project. Warehouse
limits to raw materials or finished records is integral to meeting GMPs.
construction, major HVAC changes,
goods because HVAC controls are Records must be stored securely
and similar modifications to the
ineffective there. Name and describe but retrieved easily for review. They
warehouse environment require
these nonstorage locations and must be gap-free. They must provide
additional mapping. Seasonal
modifications in the validation plan. an audit trail. Records may be paper,
changes and extreme weather may
Modify your validation protocol in electronic, or a combination. If they
justify mapping the warehouse with
light of the results from your initial are electronic records, they must
greater frequency or rescheduling
mapping test. meet the requirements of 21 CFR
a test for a more “seasonable”
Part 11 or EC Annex 11.
Regulatory Note: Modifications to temperature. For example, the
a newly commissioned warehouse validation plan may call for a test
don’t need to appear in the in July, when temperatures are
inspection record. But once your typically hottest. But if July is
company approves a validation unseasonably cool, it may make
master plan, then the plan must sense to delay mapping until a warm
document all subsequent changes. spell in August. The validation plan
9Regulations and Parenteral Drug Association:
Summary Guidance
Warehouse mapping regulations,
• PDA Technical Report No. 52 –
Guidance for Good Distribution
The keys to successful such as CFR Title 21 and comparable Practices for the Pharmaceutical
warehouse mapping include European standards, require Supply Chain (2011)
creating and following a documented evidence that an
European Commission:
environment is in a state of control,
validation plan and protocol,
suitable for the products stored • EC Guidelines on Good
with logical, scientific there. Regulatory agencies and Distribution Practice of Medicinal
justification for each step. independent organizations also issue Products for Human Use (under
Document changes to the nonbinding guidance documents, revision 2011)
plan and protocol. which provide greater detail than
Pharmaceutical Convention
regulations do in defining GMPs
Identify areas of risk in your Inspection and Pharmaceutical
and current regulatory thinking.
Inspection Cooperation Scheme:
warehouse to determine the However, even these guidance
distribution of sensors and documents lag behind advances • PIC/S GMP Guide Part I: Basic
duration of the mapping. in technology. In a race to keep up, Requirements for Medicinal
regulatory agencies and industry Program Sections 3.19 and 4.9
Select reliable technology groups worldwide constantly
• PIC/S GMP Guide Part II: Basic
suitable to the task. revise their interpretations of
Requirements for Active
GMPs, developing new regulations
Modify your storage space to Pharmaceutical Ingredients
and guidance documents. So it’s
Sections 7.42 and 10.1
make sure you can validate a imperative to keep abreast of the
controlled environment. changing standards. U.S. FDA Code of Federal
Regulations Title 21:
Document and schedule A selected list of regulations and
guidance for mapping appears • 21 CFR 820.150 Storage
mapping tests to account for
below. It’s intended to be useful but
changes in the warehouse Health Canada:
not comprehensive.
environment. Keep records • GUI 0069: Guidelines for
International Conference on
in a manner that they are Temperature Control of Drug
Harmonisation:
both secure and available for Products During Storage and
review. • ICH Q10 Pharmaceutical Quality Transportation (2011)
System (2009)
The following are other relevant
Document that your protocol
United States Pharmacopeial sources for regulations, guidance
was followed consistently, Convention: and standards.
and re-evaluate your
• USP Chapter 1079 Monitoring U.S. FDA Code of Federal
procedures periodically.
Devices – Good Storage and Regulations Title 21:
Shipping Practices (under revision
• 21 CFR Part 210 cGMPs for
2011)
Manufacturing, Processing or
• USP Chapter 1118 Monitoring Holding of Drugs
Devices – Time, Temperature, and
• 21 CFR Part 211 cGMPs for
Humidity
Finished Pharmaceuticals
International Society of
• 21 CFR Part 820 cGMPs for
Pharmaceutical Engineering:
Medical Devices
• ISPE Good Practice Guide – Cold
• 21 CFR Part 600 cGMPs for Blood
Chain Management (2011)
Products
10• 21 CFR Part 111 cGMPs for Dietary World Health Organization:
Supplements
• WHO Report 908 Appendix 2
• 21 CFR Part 11 cGMPS Electronic ASTM (formerly American Society
Records & Signatures for Testing and Materials):
• 21 CFR 211.46, .68, .142, .194 • ASTM E2500 Standard Guide
Ventilation, Air Filtration; for Specification, Design, and
Electronic Equipment, Verification of Pharmaceutical and
Warehousing; Laboratory Records Biopharmaceutical Manufacturing
Systems and Equipment (2007)
European Commission:
International Organization for
• Eudralex Volume 4 Good
Standardization:
Manufacturing Practices –
Medicinal Products for Human • ISO/IEC 17025:2005 General
and Veterinary Use, Annex 11: Requirements for the Competence
Computerized Systems (2011) of Testing and Calibration
Laboratories
U.S. FDA:
• ISO 10012:2003 Measurement
• Guidance for Industry:
Management Systems
Quality Systems Approach to
Pharmaceutical cGMP Regulations • ISO 14971:2007 Medical Devices –
(2006) Application of Risk Management
• Pharmaceutical CGMPs for the
21st Century – A Risk-Based
Approach (2004)
International Conference on
Harmonisation:
• ICH Q8 – Pharmaceutical
Development (2006)
• ICH Q9 – Quality Risk Management
(2006)
• ICH Appendix 2.4 Human and
Organizational Errors and
Criticality of Records
International Society of
Pharmaceutical Engineering:
• ISPE GAMP® 5: A Risk-Based
Approach to Compliant GxP
Computerized Systems
11For more information, visit Ref. B211170EN-A ©Vaisala 2012
This material is subject to copyright protection, with all
www.vaisala.com or contact copyrights retained by Vaisala and its individual partners. All
us at sales@vaisala.com rights reserved. Any logos and/or product names are trademarks
of Vaisala or its individual partners. The reproduction, transfer,
distribution or storage of information contained in this brochure
in any form without the prior written consent of Vaisala is strictly
prohibited. All specifications — technical included — are subject
to change without notice.You can also read
