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Introduction
The conditions under which pharmaceutical products are Particularly important are the FDA’s Predicate Rules, which
manufactured, stored and distributed are subject to stringent set stringent requirements for the manufacture, processing,
standards. Satisfying these requirements is essential for packing and storage of pharmaceutical products.
companies wishing to prove that their products have been
safely produced and are suitable for sale both at home The specific predicate rules relating to pharmaceutical
and overseas. manufacturing are:
– 21 CFR Part 210, stipulating current good manufacturing
When it comes to the use of electronic equipment in practice in the manufacture, processing, packing and
pharmaceutical production, the de facto standards are set storage of pharmaceutical products; and
by the International Society of Pharmaceutical Engineers’ – 21 CFR Part 211, setting current good manufacturing
(ISPE) Good Automated Manufacturing Practice (GAMP) practice for finished products
guidelines. Adopted by countries worldwide, these guidelines
set down the main requirements that need to be considered These rules include guidance on which aspects of
when planning and implementing computerized systems in pharmaceutical production need to be recorded, including any
pharmaceutical applications. Figure 1 on the next page process control settings, details on checking recorded data
shows the standard drivers associated with the current and specific requirements relating to the collection of batch
GAMP guidelines. production and control records.
As the world’s largest market for pharmaceutical products, Where these records are collected electronically, then
the US has led the way in developing its own interpretation 21 CFR Part 11 also applies, which aims to give electronic
of these guidelines, with the Food & Drug Administration’s records and signatures the same weight and trustworthiness
(FDA’s) good practice rules setting the standard for companies as their paper-based counterparts. A key aspect of 21 CFR
worldwide. Part 11 is its focus on security, particularly relating to the
prevention of data tampering and the ability to identify specific
individuals and events involved in the production and / or data
management processes.
The application
The application
The conditions under which pharmaceutical products are For the purposes of traceability, it is necessary to adhere
manufactured and stored can have a major impact on their to GAMP guidelines to accurately record every stage in the
quality. Factors such as temperature, humidity, air quality, production lifecycle of a product, encompassing not just the
time and production process characteristics can all have manufacturing process but also the storage and distribution
a significant impact on the final quality, and therefore the stages. In doing so, manufacturers can prove to have acted in
saleability, of a product or batch of products. accordance with best practice by building in quality from the
outset and designing failure out of the process.
Effective supplier
relationships
GAMP 5 Quality by
design (QbD)
Figure 1. GAMP 5 sets the main requirements for the use of computerized systems in pharmaceutical applications.
2 AD/RandC/005-EN | Monitoring manufacturing, production and storage environments in the pharmaceutical industry
The challenge
Product
Knowledge
Process
Knowledge Operation and
Requirements Specification Verification Acceptance
Continuous
and Design and Release
Regulatory improvement
Requirements
Company
Quality reqs.
Risk Management
Design Review
Change Management
The challenge
Manufacture, storage and distribution
GAMP guidelines advise that the manufacture, storage and Exactly how this is achieved varies according to the type
distribution stages of pharmaceutical products are monitored and size of refrigerator being used and the type of product
to ensure that any facilities involved meet the required in question. High-risk products, for example, must be
standards. Of the various parameters that need to be maintained between 2°C and 8°C and stored in precisely
carefully controlled, temperature and humidity are perhaps controlled refrigerators.
the two most critical.
For operators of a storage plant, it is necessary not only to
All parties involved in the manufacture, storage and ensure that products are stored at the right temperature,
distribution of pharmaceutical products are required to record but also that the refrigeration plant is capable of accurately
and keep details of temperatures during these processes. maintaining that temperature.
Efficient handling and processing of sensitive materials is Adopted by many countries worldwide, the UK’s Medicines
critical to the profitable manufacture of pharmaceutical and Healthcare products Regulatory Agency (MHRA)
products. GAMP encourages manufacturers to use regulations stipulate that the performance of refrigeration
measurement techniques that allow a better understanding plant used to store pharmaceutical products needs to be
of the interaction between material properties, equipment regularly checked. To achieve this, operators need to map
design and operating conditions, in processes such as their refrigeration equipment using one or more thermometers
capsule forming and drying, pan coating, parenteral and /or temperature probes to ensure that temperature is
manufacturing, sterile filling, spray and powder drying, uniformly maintained. The resulting temperatures need to be
and tablet compression. recorded as proof of compliance with the required standards.
For many products requiring storage in cool conditions, The requirement to accurately map storage temperatures
refrigeration plant is widely used, which needs to be also extends beyond refrigeration equipment to include
carefully monitored to ensure that the correct temperatures warehouses and controlled temperature rooms.
are maintained.
Monitoring manufacturing, production and storage environments in the pharmaceutical industry | AD/RandC/005-EN 3
Security and the solution
Storage rooms
Production area
Entrance
Control cabin
F
500
SM
SM500F
4 AD/RandC/005-EN | Monitoring manufacturing, production and storage environments in the pharmaceutical industry
The solution
The temperature/humidity probes are usually wall or The use of independent recorders for environmental
ceiling mounted, generally of a type that can allow full loop monitoring allows specific, independent and easily validated
calibration by being placed in the manufacturer’s calibration areas to be monitored without the requirement of validating
equipment. A regular calibration check and full calibration an entire complex Environmental Monitoring System (EMS).
adjustment facilities for the system inputs are important to
verify that the measurements made are reliable. In large storage facilities, recording probes should be placed
within the load for routine monitoring. If air distribution is not
In the case of storage, large refrigerators (in excess of 6m3) fan-assisted, the probe should be located in the part of the
and walk-in cold rooms used in high volume operations load at the highest risk from low temperatures.
should be fitted with an electronic temperature recording
device that measures load temperatures. With high volumes The placement of goods within walk-in units is also critical.
it is important that the chart, printout or direct reading should Any goods sensitive to temperatures greater than 8°C should
be checked daily and the examination recorded; in this not be stored next to the door and goods susceptible to
instance it may be easier to install an electronic recorder, temperatures below 2°C should not be placed in the airflow of
with a calibrated max/min thermometer placed inside the unit the refrigeration unit.
as a backup.
With high risk products it is important that temperatures are
The system that records the data also triggers warning and recorded on a daily basis and that probe(s) are placed within
active alarms should the accepted process parameters be the load (or within a suitable buffer) to record the load rather
exceeded. These often incorporate a time delay and / or a than the air temperature. These facilities should also be based
hysteresis. This only triggers the alarm once the parameter in an external environment where the ambient temperature
has exceeded acceptable levels by a certain amount of time, does not affect the temperature control within the unit.
helping to prevent nuisance alarms.
A small but increasing number of blood and biotechnology
The provision of Ethernet connectivity allows historical products must be stored frozen. Storage units must be
recorded data and alarm and audit trail information to be capable of maintaining the required temperature in all parts
relayed automatically to a central database where archive of the load, and temperatures should be monitored within the
and analysis, if required, can take place. load and recorded daily.
Monitoring manufacturing, production and storage environments in the pharmaceutical industry | AD/RandC/005-EN 5
What can ABB offer?
6 AD/RandC/005-EN | Monitoring manufacturing, production and storage environments in the pharmaceutical industry
SM3000
The SM3000 Multipoint Videographic Recorder features
state-of-the-art data storage and security technologies.
It enables up to 36 universal analogue inputs, communicated
inputs or math results to be recorded and displayed in a
variety of operator views. Its 8Mb onboard flash memory can
store 2.8 million samples of data. There is also the option of
Compact Flash removable memory cards, providing extensive
data storage capabilities.
DataManager Pro
ABB’s new DataManager Pro analysis software offers a
powerful tool for reviewing recorded data. Using the software,
operators can review data from multiple recorders. Functions
include the ability to compile graphical charts comparing
multiple parameters, plus a dual cursor function enabling
operators to review data for specific periods of time and
specific recorders.
Monitoring manufacturing, production and storage environments in the pharmaceutical industry | AD/RandC/005-EN 7
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