Areas of focus activities:

1. Temperature: Manufactured drugs, precursor chemicals, and active pharmaceutical ingredients

require stringent temperature control. Typically, storage temperatures range between 15-25°C
(59-77°F). Specific product categories (e.g. vaccines, medicines containing hormones) often
need freezing during storage as well as transportation. Failure to maintain such drugs within
their specified temperature controls not only reduces its efficacy but could also cause changes
in their chemical composition
2. Humidity: Moisture is a huge problem in maintaining the effectiveness of a medicine. For
example, if blood glucose strips are exposed to moisture, it would result in inaccurate readings
3. Exposure to light: Often, the chemical composition of medicines can undergo a change upon
prolonged exposure to light from the sun (ultraviolet rays). Photodecomposition, and post-drug
administration side-effects (e.g., photoallergy, phototoxicity) are other harmful effects that have
been observed

Warehouse Best Practices Mandate that:

1. Similar Product Types are to be stored accordingly

2. Unique Codes are visible
3. Correct Labelling with updated and accurate information (e.g., expired, damaged, ready for
shipment, etc)
4. Material movement within the warehouse is tracked minutely right through to the point that they
are shipped out.

Included are several pharmaceutical warehousing requirements in the GMF standards:

1. Warehouses must store drugs in a manner to prevent contamination, and that allows for
thorough inspection and cleaning of the area.
2. Each drug lot must have a unique and traceable code to allow for lot identification and lot status
identification (approved, quarantined, rejected.)
3. Each drug in the warehouse must have written procedures that describe the processes for
distribution and recalls.
4. The written procedures of each drug must describe appropriate storage conditions.
5. Appropriate storage requirements present unique challenges to pharmaceutical warehouses.
Each drug has individual storage requirements regarding temperature, lighting, and humidity.
The warehouse must follow the drug manufacturer’s storage requirements to the letter
6. Meeting storage requirements often involves setting and monitoring the environmental
parameters of a storage section’s temperature- and climate control.
7. Temperature control involves controlling and monitoring the temperature of the facility.
8. Climate control refers to the regulation of a storage unit’s temperature and humidity.

Some issues that Warehouse Managers constantly grapple with include:

1. Inventory management (reorder levels, supply-chain, packing, loading, dispatching)

2. Maintaining requisite temperatures (varies according to sections) for temperature-sensitive
products (e.g. perishables, medicines)
3. Maintaining security for goods, intellectual property, employees
4. Maintaining mandated procedures and regulations for the handling of goods.
The FDA (Food and Drug Administration) mandates a “Current Good Manufacturing Process”
(CGMP) to establish the requisite standard for drug storage and warehouses management
processes. These include:

1. Storage: detailed guidelines outlining the conditions under which each drug is to be stored
2. Tracking: maintaining careful track of all product categories and their prescribed storage and
handling protocol within the warehouse
3. Contamination: careful cleaning and inspection while in storage
4. Unique identification: all drugs must be identified and stored with their unique codes that can
be easily identified and traced. Related data such as batch size, receipt (etc.) must also be
maintained
5. Handling and distribution: Detailed guidelines outlining the process of handling and distribution
for each product (recalls to be carefully outlined too)

Maintaining the correct documentation for these is always a challenge for Warehouse Managers.

1. Storage: Defective products are often a result of poor storage procedures and inadequate
control over material movement within the warehouse. Warehouse best-practices mandate
that:
• Similar product-types are should be stored accordingly
• Unique codes are visible
• Correct labeling with updated and accurate information (e.g. expired, damaged, ready-for-
shipment (etc.)
• Material movement within the warehouse is tracked minutely right through to the point
that they are shipped out
• Addictive drugs and toxins are stored appropriately. Access is given only to approved
personnel
• Ideally, samples that are not for sale, counterfeit ingredients and materials, damaged,
returned, and recalled goods to be stored separately
• Finished goods, and unused goods are quarantined till shipped out

2. Testing: Stringent requirements for sampling rooms must be maintained as mandated by the
authorities e.g. clean instruments, PPE kits, and positive-negative air pressure to create
secure airlocks and prevent contamination.

3. Shipments: GMPs mandate that materials be reviewed per its use. Starting chemicals must
be scrutinized. Additionally:
• Stored safely, and according to prescribed storage methods
• Its supply source must be approved
• Be registered in the firm’s database of approved inventory items
• Display correct labels with the requisite information
• Must be damage-free, defect-free
• Be “quarantined” till all quality-control checks are completed

4. Tags and labels: GMP rules are very clear about maintaining the correct labels on products
and materials. They must include its standard name and its UIN (Unique Identification
Number) and this must be separate from the one assigned by its supplier.

Expiry dates, barcode trackers, color codes, products under investigation, rejected items,
approved items, finished goods ready for release, quarantined items (etc.) are just some
details that are captured via effective labeling

5. Using technology: As is the case with all industries, unless your technology and systems are
updated to modern-day methods, you would certainly operate at a tremendous disadvantage.
Often, you will probably be on the wrong side of the mandated legal procedures for the same.
 Deploying automated software, cloud technology, mobile devices, latest hardware (etc.) is an
absolute must.

6. Security: Pharmaceutical products, drugs, and their various components are always liable for
theft simply due to their high costs. Additionally, such products always have high demand,
thereby further increasing their attraction for theft.

Good Distribution Practice (GDP) and Good Warehousing Practice (GWP) are each special parts
of GMP. GDP refers specifically to the transport and distribution of the product. GWP refers to the
practices specifically within the company warehouse.

A pharmaceutical warehouse must be expertly managed and run in compliance in order for the company
to protect and distribute a quality product.

These compliant practices include control over receiving goods, quality control, storing materials,
components and products, fulfilling picking requests and shipping the product to the marketplace. These
practices must be completely traceable in order to protect the integrity and stability of the product and
its packaging.

1. GMP rules for the warehouse enable manufacturers to:

2. Protect medicines from damage during storage and transport

3. Prevent degradation of the product by exposure to adverse temperature conditions

4. Avoid mix-ups and contamination by other materials

5. Maintain product identity and traceability

6. Prevent time-expired or damaged material or product from being used

What comes into the warehouse?

The following goods generally do not appear on any production bill of materials, and have a simplified
check and release. Often, they do not have an in-house lot number applied, but this varies from
company to company.

1. Non-production consumables (non-GMP material), e.g. toilet paper, stationery

2. Production materials consumed in processing, e.g. filters, lubricants

3. Laboratory reagents, e.g. buffers, chemicals

The last two items above will usually have their own QC approval processes.

The following goods will always appear on any production or packaging bill of materials. They are each
governed by GMP quality control and release procedures. All these goods will be issued with unique lot
numbers.

1. Manufacturing starting materials and chemicals

2. Packaging components, e.g. blister pack film, bottles, caps, vials, seals

3. Printed matter, e.g. labels, cartons, inserts/leaflets, pre-printed tubes

Procedure for Receiving materials into warehouse

When starting materials first arrive at the facility, they fall under the control of the warehouse. Different
types of materials can be treated in a number of different ways. For example, materials consumed in
production need to be registered and checked for approved supplier and grade (pharmaceutical or
medical), but may or may not need a unique identifying number. Ensure that you know your Standard
Operating Procedures.

In the case of starting chemicals used in product formulation, they will always need to be checked to
see that they;

1. Arrived from an approved supplier

2. Are not damaged

3. Are correctly labeled and identified with the supplier’s lot number for traceability purposes

4. Are given a unique in-house lot number

5. Registered in inventory, and

6. Quarantined, then sampled for release testing

Some of these chemicals may also deteriorate when exposed to heat, so they may have to be stored
under controlled temperatures, or even frozen.

Typical layout of a warehouse

Warehouses are typically classified by the types of material they contain, for example, raw materials,
packaging materials, intermediate or bulk product and finished product.

A typical warehouse will contain some or all of the areas described below.

1. Quarantine area for storing goods that have not yet been inspected or tested. Materials stored
in Quarantine cannot be used or released until approved by QC.

2. Some warehouses have a Dangerous Goods storage area to ensure the safety of staff and the
facility. For example, flammable goods such as ethanol would be stored in this area. Special
storage conditions, such as flame-proof cabinets, are used here.

3. Some warehouses have a locked area for restricted goods, such as poisons and drugs of
addiction. This area is restricted to specifically authorized staff.

4. A separate area for isolating faulty or recalled goods, ensuring that they are not issued or sold
by mistake.

5. A “reject” area reserved for rejected batches.

6. The cool room is usually operated at 2°C – 8°C so temperature-sensitive materials (e.g.
vitamins) do not deteriorate.

It is important to regularly check that the cool room temperature is within normal operating ranges. The
cool room usually has a quarantine and a released area.

1. The sampling booth is the first place starting chemicals are opened. To protect the material,
the sampling room should have specific air controls to exclude outside air from entering, and to
contain any dust generated from sampling to protect the environment. Sampling implements
must also be clean before use and cleaned after each use.

Pay particular attention to the air control systems, gowning and safe handling of chemicals in this area.
 1. A “released” area for batches that have been successfully tested and passed for use.

2. A quarantine area for storing goods that have not yet been inspected or tested. Materials stored
in Quarantine cannot be used or released until approved by QC.

Use of computer systems

Often, computer systems are used to control the inspection and test status of materials and products.
If computers are used, materials and products may not need physical status labels, or even be stored
in separate areas.

Inventory status control computer systems used in warehouses must be validated for reliability and
freedom from errors.

There will be strict procedures in place and security levels instituted to ensure that information is
accurately entered. You should be familiar with the security and procedures associated with the use of
these systems,

Repacking

Some raw material supply warehouses may decide to repack larger containers of chemicals into smaller
order quantities. While this may seem a simple process, it must come under GMP controls and be
accompanied by a processing record. Repacking should be performed according to a written procedure
and only by trained staff.

Common mistakes made during repacking process?

1. The labels on the smaller bags may not give exactly the same information as the original larger
pack.

2. The repacking may take place in a room which is contaminated with other chemicals.

3. The smaller containers may not be compatible with the larger drum.

4. The re-packer may want to apply their company name and delete the original manufacturer’s
name.

5. The chemical may be hydroscopic (pick up moisture) during the repacking process.

6. The chemical may be harmful to health if not handled correctly, or the Material Safety Data
Sheet (MSDS) may not be included.

Warehouse personnel and training

Warehouse personnel need to be skilled in a number of different functions, including applying the GMP
rules specific to the warehouse, just like manufacturing personnel are trained in applying the GMP rules
related to their areas. All warehouse personnel need to be trained, even contract and casual staff
employed during peak times.

Warehouse personnel should also be trained in SOPs applicable to the warehouse’s operation.

Some examples of specific skills required relevant to warehouse personnel:

1. Pack and label stock so that it is protected during transport.

2. Interpret environmental monitoring displays such as temperature and humidity gauges.

3. Be able to ensure materials and stocks are located under their correct storage locations.
 4. Use safe handling procedures according to each chemical’s Material Safely Data Sheet
(MSDS).

5. Conduct stock takes and maintain inventory records.

6. Accurately locate and select the right stock from pick lists and orders on a first-fin, first-out
basis.

7. Recognize situations where products or chemicals may be at risk, e.g. spillage, broken pack,
missing labels.

8. Safely operate picking machinery, such as a forklift or bay picker.

9. Accurately enter stock into the computer system inventory and maintain accurate paper
records.

Preventing contamination and deterioration

1. To prevent possible contamination or deterioration of materials during warehousing, there are

some important warehouse rules that must be followed:

2. No packs should be left unsealed. This prevents possible dirt contamination from the
environment or pest infestation.

3. All chemicals and products must be stored within their labeled temperature zones, for example,
products labeled:

4. Store at 2°C-8°C.

5. Do not freeze.

6. Store below 25°C.

7. Use a first-in, first-out (FIFO) system. Chemicals and medicinal products deteriorate over time,
and generally have expiry dates. Not rotating stock could result in partly degraded or aged
materials being issued.

8. Follow the chemical spillage procedures to ensure that personnel and other products are
protected. Report all incidents to supervision.

9. Keep outer doors and exits closed whenever not in use. Outside dirt and pests may contaminate
the stock.

10. Never use material or product that is either unlabeled or not correctly labeled. If a label is
missing, it generally means the stock should not be used.

Preventing mix-ups in the warehouse

In a busy warehouse, there is daily movement of starting materials into the warehouse, daily pickups
from production, regular storage of in-process bulk goods, incoming finished products, and release of
finished stock to distributors. Space is often limited, and many warehouses can become overcrowded.

During all this movement of stock, staff have to maintain records, and sometimes apply labels to indicate
status.

As there are opportunities for mix-ups to occur on an almost daily basis, so too are there GWP rules
that help prevent these from happening:

1. Quarantine inward goods and finished goods until they are approved for release.
 2. Segregate material by their status labels (e.g., there should be only released labeled stock in
the released store).

3. Ensure that Unique Identifying Numbers and batch numbers are clearly visible and legible.

4. Wherever possible, ensure that only one type of material is stored in one location. (Note:
Different companies may have different views on this)

Material and product segregation

One of the keys to ensuring that only the correct materials or products are released is to practice good
physical segregation and/or validated electronic segregation. In the case of defective and recalled
goods, it is essential to have both physical and electronic segregation.

Physical Segregation

It is a GMP/GWP rule that goods with different statuses be physically located in different and designated
areas if a validated computer system is not used to control location. (Some companies also use physical
segregation even when they employ validated computer systems)

Physical segregation minimizes the chance of someone accidentally selecting and using the wrong
material.

Always double-check the status of the item and its location before selecting it. If the selected lot is in a
quarantine or reject location, refer the error to your supervisor.

Electronic Segregation

Many warehouses control their inventory by the use of an MRP computer system. The computer system
must be validated (be 100% reliable) and only allow access to authorized personnel.

Generally, warehouse computer systems are used to:

1. Register inward goods and their quantities, lot numbers, expiry dates, suppliers, and assign
their status (e.g. Quarantine)

2. Change the status of a lot or batch

3. Depending on the status of the lot or batch, allow or disallow planners and dispatchers from
selecting goods electronically

4. Track inventory movement to specific allocated locations in the warehouse so that only the right
material or product can be selected for use or release

5. Provide an accurate history of stock movement to allow for stock takes and traceability

In summary, the warehouse computer system serves a critical function, and staff required to use it must
be fully trained in its use. In addition, staff should never share their passwords with other staff, nor log
on or off other personnel.

Warehouse personnel have to deal with materials and products that may have different statuses, or
may change status during storage. Some materials and products may actually be damaged or defective,
and staff need to isolate these from good stock.

The following non-routine, suspect or defective goods may be encountered in the warehouse:

1. Damaged goods from stock

2. Returned goods from customers

 3. Recalled goods

4. Counterfeit products

5. “Not for Sale” samples

The rules for GMP Warehouse

A fundamental GMP control is to ensure that only approved starting materials that meet specifications
are used to formulate medicines. Patient safety depends on it. Removing the protection of status
controls will raise the risk of an error occurring.

The government regulatory agencies and their auditors are very aware that lack of control over material
movement in the warehouse can, and has, led to defective product. For this reason, they regularly
conduct inspections of the warehouse and the warehouse procedures to ensure that GMP rules are in
place.

Preventing contamination and mix-ups of materials and products are the main focus of GMP in the
warehouse.

Some general rules to prevent contamination and mix-ups are:

1. Materials must be purchased only from approved suppliers to written specifications.

2. All incoming materials must be placed into quarantine.

3. Quarantined materials must be inspected and/or tested to verify their suitability for use.

4. All materials must be labeled clearly to indicate their inspection and test status.

5. Materials must be stored safely to protect from deterioration and damage.

6. Records must be maintained for all issued material in order to ensure traceability.

Contamination

Contamination refers to the presence of any foreign substance in a product.

It may be:

1. Physical, e.g. foreign objects, dirt, dust, pollens

2. Chemical, e.g. cleaning agents, lubricants, impurities, degradation products

3. Microbiological, e.g. bacteria, moulds, spores, yeasts

Housekeeping in the warehouse

A key to a successfully operated warehouse is good housekeeping. The warehouse is generally a very
busy place, with constant movement of inventory in and out, as well as to different warehouse locations
internally.

Good housekeeping, which essentially means “Everything in its place”, minimizes the opportunity for
mix-up of goods, reduces the possibility of dispatch or issue of incorrect goods, and improves
warehouse safety.

Pictured here is on area specifying a no-walk zone. Forklifts are constantly used in this area, and are
potentially dangerous. In addition to good housekeeping, warehouse personnel should pay attention to
safety rules, including what type of safety clothing that should be worn.
Material identification information

Each separate material received should be labeled with a standard name and a Unique Identifying
Number (UIN). These are used throughout storage and processing to identify that material. In order to
prevent confusion with product batches, the UIN is generally not called a batch number, and should not
be the same as the supplier’s lot number.

Supplier’s batch number

Within each delivery, containers bearing different manufacturers’ batch or lot numbers should be
separate. This will help trace any contamination or other problem back to a supplier’s batch and make
it easier to isolate the finished product containing suspect material.

Each group bearing the same batch, lot, or equivalent number in a single delivery can be regarded as
the same material. Subsequent deliveries of the same manufacturer’s batch or lot number should also
be regarded as separate materials, since the handling and transport may have affected their quality.

Standard name

The standard name refers to the unique approved name listed in the company’s standard names
register. The standard name is the same one that is used in the product formulation bill of materials.
For example, sodium chloride can also be generically called salt or sodium salt. Standardizing the name
internally eliminates any confusion.

The term “USP” refers to the grade or quality of the material. Generally, chemicals will be labeled “USP”,
“BP”, or “EP” grade to indicate that they ere pharmaceutical grade.

Material item code

The material item code is linked to the Standard Name, and is used in the Master Batch Record and
formulation. This code also corresponds with the barcode, and usually helps identify the approved
supplier and grade of the material.

UIN (Unique Identifying Number)

The UIN (Unique Identifying Number) is alternately called the Goods Inward Number (GIN), lot number,
or batch number. The number is critical because it uniquely identifies and allows traceability of that
consignment of material. The UIN is recorded in the laboratory, on the computer system, and in
production when a product is formulated.

Expiry date

The expiry date indicates the date after which the goods cannot be guaranteed to be safe for use.
Clearly, once goods have expired, they must be placed in reject areas and not used.

Storage conditions

Materials and products can degrade if not stored under the approved storage conditions. For finished
products, storage conditions are registered with the government, making it a legal requirement to store
them in compliance.

Barcode

Some companies apply a unique barcode, providing a second unique identifier for the material and
product. The barcode is used to electronically scan the identity of the item before issue.

Status labels
In addition to the identification information, each lot requires a status label, so that the status of any
material is evident. Some examples of physical status labels are below. Note the use of the different
colors. (Note: Different companies may have different colors for the types of status labels used)

Status labels may be either:

1. Physical labels on the container

2. Electronic fields on a database

3. Combination of physical and electronic

Be familiar with the system your company uses to ensure that only released materials are used.

Before any lot may be used in manufacturing, it must be released for use QC. Once a lot has passed
inspection and testing, QC will change the status from “Hold”/”Quarantine” to “Released”/”Approved”.

Quarantine label

This label is used when the goods have not yet been tested and released for use by the laboratory.
Materials labeled Quarantine should not be used.

Hold label

The Hold label indicates the material may have a problem and is under investigation. Do not use under
any circumstances.

Release label

The Released label indicates the material is suitable for use or released for supply. The batch has been
tested and cleared by the Quality Department.

Approve label

The Approved label indicates the material is suitable for use or released for supply. The batch has been
tested and cleared by the laboratory.

Reject label

The Rejected label indicates that the batch has been assessed as unacceptable or defective. Never
use these materials. They should be located in separate, locked area

Control of product labels

The control of product labels is a crucial port of GMP, since customers may be adversely affected by
mislabeled product. All product labels must therefore be strictly controlled. Some of these controls
include:

1. Each different type of label is clearly identified and segregated in the label store to prevent mix-
ups.

2. Access to the label store must be restricted to authorized personnel.

3. There should be no loose approved or released labels in the store.

4. Any unused or damaged labels should be returned to the Quality Department.

5. “Approved” or “Released” labels should only be issued by the Quality Department.

 6. Before the release of labels, they must be checked and double-checked against the work order
to verify the:

7. Product name and code

8. Label identity and version number

9. Coded batch number and expiry date

Only when all the checks have been satisfactorily completed can labels be taken into the packaging
area.

GMP storage requirements for warehouse

Staring materials and components must be stored in designated locations.

Some materials are required to have additional safety and security procedures. For example, the
following goods must be locked up or otherwise secured from unauthorized access:

1. Printed packaging materials

2. Drugs of addiction, antibiotics, and highly potent drugs

3. Poisons and flammable goods

4. Rejected and recalled materials

5. Returned goods

Keep powders, liquids, and corrosive and flammable materials separate.

Dangerous goods areas should be specially equipped to prevent contamination and spills.

How to keep the warehouse Clean

GMP rules state that warehouses storing raw materials, components, printed matter, and finished goods
must be kept clean, dry, and orderly at all times.
This involves, but is not limited to:

1. Protecting receiving areas from the weather

2. Checking regularly to ensure that containers and packs are sealed properly

3. Cleaning the facility regularly

4. Cleaning up spills immediately

The exterior of inward goods containers may also need to be cleaned before storage.

Protecting goods from deterioration

To protect goods from deterioration:

1. Store goods at the temperatures specified on their labels.

2. Monitor and alarm freezers and refrigerators.

3. Monitor temperatures in other areas where goods requiring specific storage conditions are
being stored.
 4. Review all records; analyze and file as appropriate.

5. Investigate all deviations and assess their impact on product suitability.

Protecting raw materials

Because raw materials may deteriorate on storage or become contaminated if stored incorrectly, the
storage conditions are critical to product purity. In order to protect raw materials, there are some specific
and important GMP rules relating to this:

1. Separate quarantine and reject areas.

2. The storage environment should be temperature-controlled.

3. Store goods off the floor and away from walls.

4. Employ a system that identifies material about to expire, so that it can be retested if necessary.

5. Periodically inspect stockrooms for past-expiry or expired stock, cleanliness, housekeeping,

and pest control.

6. Seal over all opened containers to protect from the environment.

7. Ensure that there is a cleaning program for each separate area in the warehouse, including for
external areas, gangways, shelving, and racking.

Pest control

Some of the pests that are attracted to pharmaceutical warehouses include rats, mice, birds, ants, and
cockroaches. For example, stored goods can be contaminated by bird or rodent droppings. Therefore,
GMP rules require that a manufacturing facility has:

1. A nominated pest control officer

2. Specific instructions or agreements with pest control companies

3. Maps showing bait locations

4. Documentation of all pest control treatments

5. Having frequent waste collections

Environmental regulations and OH&S also require companies to protect personnel and the surrounding
environment from the chemicals used in pest control programs.

An effective pest control program involves:

1. keeping track of any sightings of pests between visits by the pest control companies

2. assigning someone to accompany the pest control agent when they are on site

3. using only approved pesticides

Controlling air supply in the warehouse

The warehouse links the outside environment to the inside production facility. Therefore, the warehouse
becomes a barrier to prevent dirt, dust, particles, moisture and pests from entering the building.

In order to separate the inner production area from the outside, warehouses generally have specific
designs, and rely upon employees keeping doors shut wherever possible.
Outside Air

The outside air is of course not controlled in any way. If the factory is left open, wind will blow
contamination into the factory, so it is important that the outer door is kept shut when not in use. The
outer door provides the first point of protection for the warehouse and the production area.

Receipt Area

This is where goods are unloaded off the delivery truck and assessed before being brought into the
warehouse. Notice that this area has an outer roller door and an inner curtain in order to prevent outside
dirt or dust from entering the warehouse. An important GMP rule is to not have both the outer roller door
and the inner barrier open at the same time. This area is sometimes referred to as a “black” zone.

This area is also the first point where outer bags and cartons are cleaned down, so that minimal dirt is
transferred to the warehouse itself. If goods are unclean or damaged, they should not be sent into the
warehouse.

Warehouse area

The warehouse itself is not pressure-controlled, but is cleaner than the receipt area. In the warehouse,
goods should be stored off the floors and away from walls, because moisture may be taken up through
concrete walls and floors. This area is sometimes referred to as a “grey” zone since it is cleaner than
outside, but still not clean enough to expose products to the environment.

Production Area

Some companies refer to the production area as a “white” or “clean” zone, where only cleaned materials
may be taken. Generally, goods transported to this area are on plastic pallets, since wooden pallets
cannot be cleaned and can harbor fungus, mould, and bacterial contamination. The production zone is
pressure-controlled to provide an air barrier to dirt and particles entry. In order to maintain positive
pressure, it is critical to keep the doors between the production and warehouse areas closed.

Before materials are taken into the production area, the outer cartons that had arrived on the truck are
generally removed, where possible, as an added precaution. Most companies also have different dress
codes when moving from a grey zone to a white zone.

Importance of controlling storage temperature

Temperature storage controls are important in the warehouse in order to ensure product integrity
throughout the product’s shelf life. Medicinal products damaged by exposure to extremes of
temperature may escape detection, resulting in physical damage and/or loss of therapeutic effect. Worst
of all, it may not be obvious at all.

For temperature-controlled warehouses, companies are expected to create a temperature map of the
facility. The map is used to identify the best places in the warehouse to store goods. An initial study
when creating this map will reveal where problems would most likely be encountered, e.g., storing
goods against north-facing walls, close to room heaters, close to windows or near the roof.

After initial mapping, temperatures are routinely monitored on a continuous or daily basis. This
monitoring may reveal seasonal patterns where temperatures may rise or fall outside approved limits.
It is important, then, to continue to review temperature profiles in the warehouse over time, particularly
during summer and winter. Some companies monitor using an electronic building management system.

Ambient temperature storage

The terms “room” or “ambient” temperature storage conditions have different meanings to different
companies and different regulators. Itis now more common the use the term “temperate” storage.
Temperate storage has recently been redefined as a storage temperature of between 15°C and 30°C,
with occasional excursions above that range.
Temperate storage controls vary from product to product, however, many licensed products stipulate
an upper limit of 25°C with no lowerlimit apart from “protect from freezing”. Inspectors have indicated
that 8°C to 15°C is acceptable temperate storage.

Additional requirements for temperature control

1. The conditions of storage for the goods should be compatible with the storage conditions
specified on their labels.

2. Controlled storage environments should be monitored, using suitable temperature recording

devices. All records should be reviewed and filed, with their results tabulated and analyzed.

3. Refrigerated and freezing storage environments should be fitted with both an alarm and a visual
signal. This signal should permit resetting only by an authorized person,

4. If any temperature is found to have deviated outside the relevant recommended conditions for
an extended time, the manufacturer of the goods should be contacted and the suitability of the
product for use resolved.

5. Equipment used for monitoring temperature should be calibrated on a regular basis to ensure
their accuracy.

How to create a temperature map

A simple temperature control example involves the physical location of material storage in the
warehouse. The higher up in the warehouse a material is stored, the hotter the temperature the goods
will be exposed to, so an physical space nearer the ceiling without temperature controls will be
inappropriate to store goods that need to be kept cool.

1. Study the temperature profile of the premises, and identify potential “hot” and “cold” areas.

2. Study the areas of greatest potential risk using calibrated temperature and humidity monitoring
instruments.

3. Develop a temperature mapping validation protocol.

4. Based on initial findings, commence monitoring on a regular basis.

5. Produce a temperature map of the premises.

6. Review the hot and cold areas when outside temperatures are extreme, for example, in summer
and winter.

7. Review the controls of heating and cooling systems.

8. Ensure an action plan exists in the event of temperatures becoming compromised.

Cold storage

Cold storage refers to the storage of products requiring a storage temperature of 2°C-8°C, or when
material is required to be stored frozen (e.g. below -20°C or below -70°C).

For a successful cold storage operation, the facility must select the right temperature recording
instrumentation, validate its processes, and maintain documentation of records and procedures,
including responding to alarm conditions.

Instruments used in the warehouse

The selection of recording instruments is vital. The instruments must be easily read, and the data must
be retrievable. The instruments must be calibrated to a national standard (the company should retain a
copy of the calibration certificate for the equipment), and a high/low temperature alarm should be
incorporated. Max/min thermometers are usually not acceptable.

Both air and product temperatures should be recorded. Note that air temperature can fluctuate
considerably more than product (often called “load”) temperature.

Validation and documentation of temperature control

1. Validation efforts must:

2. Prove that temperature mapping checks for areas of extreme temperatures.

3. Check on temperature variations during use.

4. Demonstrate performance in the event of a power failure.

5. Demonstrate the function of alarms.

Specific procedures that need to be incorporated include:

1. Checking temperature records at the start of the waking day, and recording these checks in a
log

2. What to do when certain staff are absent

3. Responding to alarm conditions

When reviewing the cold storage controls, a program should be set up to review cold store temperature
records both weekly and monthly as part of a self-inspection program.

Monitoring alarms

Out-of-hours alarm signals are often sent to remote contractors or security offsite. It’s therefore very
important to ensure the alarm system is operating reliably, as repeated false signals may result in a real
signal being ignored. There are many industry examples of degraded stock due to late or no response
to electrical failures in warehouses. The alarm system should operate independently of the main
electrical system.

There must be a written procedure on how to respond and who to inform when a temperature alarm
monitor signals a problem. This procedure should cover initial action (e.g. quarantining the cold store)
and subsequent action. There should be an available and current list of emergency numbers to call,
and there should be a backup plan to relocate any products are risk of deterioration (e.g. frozen stock).
Any response must be immediate, so the procedure should ensure that weekends are addressed as
well.

Protecting sensitive materials

Many companies (particularly companies manufacturing biologicals and vaccines) handle, store, and
transport temperature-sensitive raw materials and finished products. The protection of temperature-
sensitive products is critical to their effectiveness and safety.

Products can be degraded by excessive heat, moisture, light, or repeated freeze/thawing cycles.

Freezers

Frozen materials are usually stable at -20°C and below, though some materials require freezing at -
80°C. If the temperature rises, it will probably do so slowly over several hours. Once the temperature
rises above a certain point, some ot the frozen materials will start to deteriorate or degrade. There must
be a written action plan that includes a contingency for relocation if the temperature continues to rise.

Automatic defrost refrigerators

Some cold storage refrigerators have an automatic nightly defrost cycle, these refrigerators may not be
suitable, as many frozen products can partially melt then re-freeze, causing them to deteriorate and
degrade.

Heat and moisture

Almost all medicinal products are sensitive to heat and will degrade at higher temperatures. Some
products will degrade at room temperature, while others can withstand temperatures above 30°C for
prolonged periods. It is practically impossible to know which products are at risk or degrading at which
temperatures.

All products must undergo stability studies to prove that they will not degrade under the approved
storage conditions.

GMP rules require that products be only stored within approved temperature ranges. If the product is
exposed to excessive heat, a deviation notice should be raised.

Some products may absorb moisture from the atmosphere it they are not properly sealed. One of the
main causes of moisture problems comes from incorrect storage of products directly on concrete floors
and walls, as the product packaging can absorb moisture from these surfaces.

Light

Some products are “photolytic”, that is, they may degrade it they are exposed to light for prolonged
periods. Be alert to packages that state “Protect from light” and ensure that they are completely sealed.