Role of the Warehouse in Pharmaceuticals Manufacturing
The quality of a pharmaceutical product is defined as one that is pure, correctly identified, effective and safe to use. Customers and patients have an ethical (and legal) right to expect quality pharmaceutical products.
The warehouse plays a pivotal role in manufacturing quality products, as it is responsible for all incoming goods (including labeling and packaging) and for releasing finished products. Therefore, there are GMP rules in place to ensure that materials are handled and stored properly, while appropriate documentation is maintained.
GWP vs GDP
GWP refers to the practices specifically within the company warehouse.
GDP refers specifically to the transport and distribution of the product.
- 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.
- GDP and GWP each have their own legal definition end regulations. These regulations recognize that product quality can be significantly impacted offer manufacturing and packaging have taken place.
- In this module, “GMP” for the warehouse incorporates practices, rules, and regulations spanning GMP, GDP, and GWP.
Once a finished product is received into the warehouse, it does not undergo any further inspections or quality control tests. If the product is degraded or damaged at this point, there is nothing that stops it from being given to the patient. The warehouse must rely upon procedures and well-trained staff to ensure that products arrive safely and with the same quality as when they left manufacturing.
There have been many cases of product being affected by poor warehouse storage conditions or rough handling on transport. Biopharmaceutical products often have temperature-sensitive active ingredients that break down or degrade if exposed to heat or light, thus becoming ineffective.
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.
GMP rules for the warehouse enable manufacturers to:
- Protect medicines from damage during storage and transport
- Prevent degradation of the product by exposure to adverse temperature conditions
- Avoid mix-ups and contamination by other materials
- Maintain product identity and traceability
- 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.
- Non-production consumables (non-GMP material), e.g. toilet paper, stationery
- Production materials consumed in processing, e.g. filters, lubricants
- 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.
- Manufacturing starting materials and chemicals
- Packaging components, e.g. blister pack film, bottles, caps, vials, seals
- 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;
- Arrived from an approved supplier
- Are not damaged
- Are correctly labeled and identified with the supplier’s lot number for traceability purposes
- Are given a unique in-house lot number
- Registered in inventory, and
- 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.
- 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.
- 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.
- Some warehouses have a locked area for restricted goods, such as poisons and drugs of addiction. This area is restricted to specifically authorized staff.
- A separate area for isolating faulty or recalled goods, ensuring that they are not issued or sold by mistake.
- A “reject” area reserved for rejected batches.
- 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.
- 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.
- A “released” area for batches that have been successfully tested and passed for use.
- 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,
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?
- The labels on the smaller bags may not give exactly the same information as the original larger pack.
- The repacking may take place in a room which is contaminated with other chemicals.
- The smaller containers may not be compatible with the larger drum.
- The re-packer may want to apply their company name and delete the original manufacturer’s name.
- The chemical may be hydroscopic (pick up moisture) during the repacking process.
- 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:
- Pack and label stock so that it is protected during transport.
- Interpret environmental monitoring displays such as temperature and humidity gauges.
- Be able to ensure materials and stocks are located under their correct storage locations.
- Use safe handling procedures according to each chemical’s Material Safely Data Sheet (MSDS).
- Conduct stock takes and maintain inventory records.
- Accurately locate and select the right stock from pick lists and orders on a first-fin, first-out basis.
- Recognize situations where products or chemicals may be at risk, e.g. spillage, broken pack, missing labels.
- Safely operate picking machinery, such as a forklift or bay picker.
- Accurately enter stock into the computer system inventory and maintain accurate paper records.
Preventing contamination and deterioration
To prevent possible contamination or deterioration of materials during warehousing, there are some important warehouse rules that must be followed:
- No packs should be left unsealed. This prevents possible dirt contamination from the environment or pest infestation.
- All chemicals and products must be stored within their labeled temperature zones, for example, products labeled:
- Store at 2°C-8°C.
- Do not freeze.
- Store below 25°C.
- 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.
- Follow the chemical spillage procedures to ensure that personnel and other products are protected. Report all incidents to supervision.
- Keep outer doors and exits closed whenever not in use. Outside dirt and pests may contaminate the stock.
- 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:
- Quarantine inward goods and finished goods until they are approved for release.
- Segregate material by their status labels (e.g., there should be only released labeled stock in the released store).
- Ensure that Unique Identifying Numbers and batch numbers are clearly visible and legible.
- 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.
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.
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:
- Register inward goods and their quantities, lot numbers, expiry dates, suppliers, and assign their status (e.g. Quarantine)
- Change the status of a lot or batch
- Depending on the status of the lot or batch, allow or disallow planners and dispatchers from selecting goods electronically
- 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
- 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:
- Damaged goods from stock
- Returned goods from customers
- Recalled goods
- Counterfeit products
- “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:
- Materials must be purchased only from approved suppliers to written specifications.
- All incoming materials must be placed into quarantine.
- Quarantined materials must be inspected and/or tested to verify their suitability for use.
- All materials must be labeled clearly to indicate their inspection and test status.
- Materials must be stored safely to protect from deterioration and damage.
- Records must be maintained for all issued material in order to ensure traceability.
Contamination refers to the presence of any foreign substance in a product.
It may be:
- Physical, e.g. foreign objects, dirt, dust, pollens
- Chemical, e.g. cleaning agents, lubricants, impurities, degradation products
- 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.
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.
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.
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.
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.
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:
- Physical labels on the container
- Electronic fields on a database
- 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”.
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.
The Hold label indicates the material may have a problem and is under investigation. Do not use under any circumstances.
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.
The Approved label indicates the material is suitable for use or released for supply. The batch has been tested and cleared by the laboratory.
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:
- Each different type of label is clearly identified and segregated in the label store to prevent mix-ups.
- Access to the label store must be restricted to authorized personnel.
- There should be no loose approved or released labels in the store.
- Any unused or damaged labels should be returned to the Quality Department.
- “Approved” or “Released” labels should only be issued by the Quality Department.
- Before the release of labels, they must be checked and double-checked against the work order to verify the:
- Product name and code
- Label identity and version number
- 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:
- Printed packaging materials
- Drugs of addiction, antibiotics, and highly potent drugs
- Poisons and flammable goods
- Rejected and recalled materials
- 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:
- Protecting receiving areas from the weather
- Checking regularly to ensure that containers and packs are sealed properly
- Cleaning the facility regularly
- 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:
- Store goods at the temperatures specified on their labels.
- Monitor and alarm freezers and refrigerators.
- Monitor temperatures in other areas where goods requiring specific storage conditions are being stored.
- Review all records; analyze and file as appropriate.
- 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:
- Separate quarantine and reject areas.
- The storage environment should be temperature-controlled.
- Store goods off the floor and away from walls.
- Employ a system that identifies material about to expire, so that it can be retested if necessary.
- Periodically inspect stockrooms for past-expiry or expired stock, cleanliness, housekeeping, and pest control.
- Seal over all opened containers to protect from the environment.
- Ensure that there is a cleaning program for each separate area in the warehouse, including for external areas, gangways, shelving, and racking.
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:
- A nominated pest control officer
- Specific instructions or agreements with pest control companies
- Maps showing bait locations
- Documentation of all pest control treatments
- 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:
- keeping track of any sightings of pests between visits by the pest control companies
- assigning someone to accompany the pest control agent when they are on site
- 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.
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.
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.
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.
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
- The conditions of storage for the goods should be compatible with the storage conditions specified on their labels.
- Controlled storage environments should be monitored, using suitable temperature recording devices. All records should be reviewed and filed, with their results tabulated and analyzed.
- 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,
- 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.
- 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.
- Study the temperature profile of the premises, and identify potential “hot” and “cold” areas.
- Study the areas of greatest potential risk using calibrated temperature and humidity monitoring instruments.
- Develop a temperature mapping validation protocol.
- Based on initial findings, commence monitoring on a regular basis.
- Produce a temperature map of the premises.
- Review the hot and cold areas when outside temperatures are extreme, for example, in summer and winter.
- Review the controls of heating and cooling systems.
- Ensure an action plan exists in the event of temperatures becoming compromised.
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
Validation efforts must:
- Prove that temperature mapping checks for areas of extreme temperatures.
- Check on temperature variations during use.
- Demonstrate performance in the event of a power failure.
- Demonstrate the function of alarms.
Specific procedures that need to be incorporated include:
- Checking temperature records at the start of the waking day, and recording these checks in a log
- What to do when certain staff are absent
- 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.
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.
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.
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.