A pharmaceutical product’s quality is defined as being pure, accurately identified, safe and effective. Patients and customers have the legal (and ethical) right to expect high-quality pharmaceutical products.
Warehouses play a key role in the manufacturing of quality products. They are responsible for receiving all goods, including packaging and labeling, and for releasing products. GMP rules are in place to ensure materials are stored and handled properly.
Comparison of GWP and GDP
GWP refers specifically to practices within the company’s pharmaceutical warehousing.
GDP is the transportation and distribution of the product.
- GMP includes Good Distribution Practice (GDP), and Good Warehousing Practices (GWP). GDP refers to the transportation and distribution of the product. GWP refers specifically to the practices within the company warehouse.
- Each GDP and GWP has its own legal definitions and regulations. These regulations recognize the potential for product quality to be greatly affected if manufacturing and packaging have occurred.
- This module explains that “GMP” refers to the warehouse’s procedures, rules, and regulations. It includes GMP, GDP, and GWP.
- After a product has been delivered to the warehouse, it is not subject to any quality control or inspections. There is no way to stop the product from being delivered to the patient if it is damaged or degraded at this stage. To ensure products arrive safe and in the same condition they were when they left manufacturing, warehouse staff must follow procedures and be well-trained.
Poor warehouse storage conditions and poor handling during transport have led to many product damage cases. Biopharmaceutical products often have temperature-sensitive active ingredients that break down or degrade if exposed to heat or light, thus becoming ineffective.
To ensure the quality of a product, a pharmaceutical warehouse must be managed well and maintained in compliance.
These practices are designed to ensure that goods are received safely, quality is maintained, products are stored properly, picking orders are fulfilled, and the product is shipped to the market. To protect the integrity and stability of the product’s packaging and packaging, these practices must be easily traceable.
GMP rules allow manufacturers to:
- Protect medicines during transport and storage from possible damage
- Avoid exposing the product to extreme temperatures.
- Avoid contamination by other materials and mix-ups
- Product identity and traceability must be maintained
- Do not use time-expired, damaged or ruined material.
What goes into the warehouse?
These goods are not included on any production bills of materials and have a simplified release and check. They are not often assigned an in-house lot number, although this can vary from one company to the next.
- Non-production consumables (non-GMP material), e.g. toilet paper, stationery
- Producing materials used in processing, e.g. Filters, lubricants
- Laboratory reagents (e.g. buffers, chemicals
- These items will often have their own QC approval process.
These goods will always be on any production or packaging bill. Each one is subject to GMP quality control procedures and release procedures. Each lot number will be unique for all these goods.
- Chemicals and starting materials for manufacturing
- Packaging components, e.g. Packaging components, e.g., blister pack film, bottles, and caps, vials and seals
- Print matter, e.g. Labels, cartons, inserts/leaflets, and pre-printed tubes
- Procedure for receiving materials into the warehouse
The warehouse is responsible for receiving starting materials when they arrive at the facility. There are many ways to treat different types of materials. Materials used in production must be registered and checked to ensure that they are approved as a supplier or grade (pharmaceutical, medical). However, each material may not require a unique identification number. Make sure you are familiar with your Standard Operating Procedures.
Start chemicals that are used in product formulation will need to be inspected to ensure they work properly.
- Proven supplier
- Do not damage
- Correctly labeled and identified with supplier’s lot number.
- Are given a unique in-house lot number
- Added to inventory
- Then, the samples are taken for release testing.
- Some chemicals can also be damaged by heat so they should be kept at controlled temperatures or frozen.
A typical layout for a warehouse
Warehouses are usually classified according to the type of material they hold, such as raw materials, packaging materials and intermediate or bulk products.
One typical warehouse may contain all or some of the following areas.
- You can store goods in Quarantine until they are inspected and tested. Materials kept in Quarantine can’t be used or released until they have been approved by QC.
- To ensure safety, some warehouses have Dangerous Goods Storage Areas. This area could be used to store flammable goods like ethanol. Here, special storage conditions like flame-proof cabinets are used.
- Some warehouses contain a locked area that can be used to store restricted goods such as drugs of addiction and poisons. This area is only accessible to authorized personnel.
- There is a separate area to identify defective or recalled goods and ensure that they are not sold or issued by mistake.
- Reject area for batches that have been rejected.
- The cool room is usually operated at 2degC – 8degC so temperature-sensitive materials (e.g. Vitamins do not deteriorate
- Regularly check that the temperature in your cool room is within acceptable operating temperatures. A cool room typically has a quarantine area and a release area.
The first place that chemicals are opened is the sampling booth. The sampling room must have air controls that prevent outside air from entering and contain dust from sampling in order to protect the material. Also, sampling instruments must be cleaned before each use.
Particular attention should be paid to the area’s air control systems, safe handling of chemicals, and gowning.
This is an area that has been released for batches that have been tested and approved for use.
Quarantine is a place to store goods that haven’t been tested or inspected yet. Materials kept in Quarantine are not allowed to be released or used until they have been approved by QC.
Computer systems are used
Computer systems are often used to monitor and control the status of products and materials. Computers can be used to monitor the status of materials and products.
For reliability and avoidance of errors, warehouse inventory status control systems must be validated.
To ensure an accurate information, there will be strict procedures and security measures in place. These systems have security requirements and procedures that you should know.
Some raw material warehouses might decide to repackage larger containers of chemicals into smaller quantities. Although this might seem like a straightforward process, it should be done under GMP control and accompanied by a processing record. Only trained staff should perform the repackaging according to a written procedure.
Common mistakes made during the repacking process?
- You may not find the exact same information on smaller bags as on the larger ones.
- Repacking can take place in a room that is contaminated by other chemicals.
- Some containers are not compatible with larger drums.
- The repacker might want to use their company name, but delete the name of the original manufacturer.
- The chemical could be hygroscopic, meaning it may pick up moisture during the repackaging process.
- If the chemical is not handled properly, it could be dangerous to your health.
Training and staffing for warehouse personnel
Warehouse workers need to be proficient in many different functions. They should also know how to apply the GMP rules for their area. Every warehouse employee, including casual and contract staff, must be trained.
SOPs should be taught to warehouse workers.
Here are some examples of the skills that warehouse workers need:
- Label and pack stock to protect it during transport.
- Interpret environmental monitoring indicators such as humidity and temperature gauges.
- You must be able to locate materials and stocks in the correct storage locations.
- Follow the Material Safely Data Sheets (MSDS) for each chemical to ensure safe handling.
- Keep inventory records and conduct stocktakes
- Select the correct stock from the picklist and orders.
- Recognize potential dangers in products and chemicals, such as spillage, broken packs, missing labels.
- Operate picking machines safely, such as a bay picker or forklift.
- Correctly enter stock into the computer inventory system and keep accurate records on paper.
Prevention of contamination and deterioration
These warehouse rules are important to ensure that materials do not become contaminated or degraded during warehousing.
- Packs should never be left un-sealed. This will prevent dirt contamination and pest infestation.
- All products and chemicals must be kept within the temperature zones they are labeled.
- Keep at 2degC-8degC
- Do not freeze
- Keep below 25°C
- Use a first in, first out (FIFO) system. The expiry dates for medicines and chemicals can deteriorate over time. Inadequate rotation stock could lead to partially degraded or old materials being issued.
- To ensure the safety of personnel and products, follow the chemical spillage procedure. All incidents should be reported to the supervisor.
- When not in use, keep the outer doors and exits locked. Stocks can be contaminated by pests and dirt from the outside.
- Material or products that are not properly labeled should never be used. A missing label generally indicates that the stock should be avoided.
Avoiding warehouse mix-ups
A busy warehouse is a place where there is a lot of activity. There are daily movements of raw materials into the warehouse and daily pick-ups from production. In-process bulk goods are stored in regular intervals. Finally, the finished stock is released to distributors. Many warehouses can get crowded because of limited space.
Staff must keep records and apply labels to indicate stock status during all the stock movements.
There are many opportunities for mix-ups to happen almost every day. GWP rules help to prevent this from happening.
- Quarantine inward and finished goods are subject to quarantine until they have been approved for release.
- Segregate material based on their status labels (e.g. there should only be released labeled stock at the store).
- Make sure that Unique Identifying numbers and batch numbers are easily visible and legible.
- As much as possible, only one type of material should be kept in any one place. This is a matter that may be discussed differently by different companies.
Material and product segregation
Good physical segregation is key to ensuring only correct products or materials are released. It is important to have both electronic and physical segregation in the event of defective or recalled goods.
GMP/GWP rules require that goods of different statuses are physically located in designated areas if no validated computer system is used to determine location. Even though they use validated computer systems, some companies still employ physical segregation.
The possibility of an individual accidentally choosing and using the wrong material is minimized by physical segregation.
Before you select an item, make sure to check its status and whereabouts. Refer to your supervisor if the lot you have selected is in a reject or quarantine area.
Many warehouses use an MRP computer system to manage their inventory. The computer system should be 100% reliable and validated. Only authorized personnel can access it.
Warehouse computer systems are generally used to:
- Register inward goods, their quantities, lot numbers, and expiry dates, as well as suppliers. Assign their status (e.g. Quarantine
- Modify the status of a batch or lot
- The status of the lot/batch determines whether planners or dispatchers can select goods electronically.
- You can track inventory movements to certain locations within the warehouse so you can select the right product or material for use.
- To allow stock-taking and traceability, provide a detailed history of stock movements
- The warehouse computer system serves an important function and all staff must be trained to use it. Staff should not share passwords with others, nor log in or out of other employees’ computers.
Warehouse staff must deal with products and materials that have different statuses or might change during storage. Staff must be able to distinguish between defective and damaged products and materials.
These non-routine, suspect, or defective goods could be found in the warehouse
- Stock damaged goods
- Customers can return goods
- Recalled goods
- Counterfeit products
- Samples “Not for sale”
- GMP Warehouse Rules
GMP controls must ensure that only approved start materials are used in the formulation of medicines. It is vital for patient safety. The risk of an error happening by removing the protection of status controls is increased.
Auditors and government agencies are well aware of the possibility that warehouse material movement can lead to product defects. They regularly inspect the warehouse to make sure that GMP rules are being followed.
GMP is the warehouse’s main focus.
These are some general guidelines to avoid contamination and misinterpretation.
- Only approved suppliers can be used to purchase materials that meet the written specifications.
- All inbound materials must be quarantined
- To verify the suitability of Quarantined Materials for Use, they must be inspected/tested.
- To indicate the status of materials under inspection or testing, labels must clearly be placed on them.
- To prevent deterioration or damage, materials must be kept safe.
- To ensure traceability, all material must be kept in records.
Contamination is the presence of any foreign substances in a product.
It could be:
- Physical, e.g. foreign objects, dirt, dust, pollens
- Chemical, e.g. Chemical, e.g.
- Microbiological, e.g. Microbiological, e.g. bacteria, molds, spores and yeasts
- The warehouse has housekeeping
Good housekeeping is key to a well-run warehouse. Warehouses are often very busy places with constant inventory movement in and out as well as different warehouse locations within the building.
Good housekeeping, which basically means “Everything in its the place”, reduces the chance of misplaced goods, decreases the risk of dispatching or issuing incorrect goods, and improves warehouse safety.
This is an area that has been designated as a no-walk zone. This area is a potential danger zone for forklifts. Warehouse workers should practice good housekeeping and be aware of safety rules. This includes what safety clothing they should wear.
Material identification information
Every piece of material should be identified with a unique identifier number (UIN) and a standard name. These numbers are used to identify the material during storage and processing. To avoid confusion with product batches, the UIN should not be confused with the supplier’s lot number.
Batch number of the supplier
Containers with a different lot or batch numbers from different manufacturers should be kept separate in each shipment. This will allow you to trace contamination back to the supplier’s batch, and help isolate the suspect material from the final product.
A single shipment can contain multiple groups that have the same batch, lot, or equivalent number. These can all be considered the same material. Because of possible quality issues with transport and handling, subsequent deliveries from the same manufacturer’s batch number or lot number can also be considered separate materials.
The company’s unique approved name is the standard name. The product formulation bill will use the standard name. You can also call sodium chloride salt, or sodium salt. Any confusion can be eliminated by standardizing the internal name.
The material’s grade or quality is known as “USP”. To indicate their pharmaceutical grade, chemicals are usually labeled with the “USP”, “BP”, and “EP” grades.
Material item code
The material item code, which is linked to the standard name, is used in the Master Batch Record as well as formulation. This code is also linked to the barcode and helps to identify the supplier and the grade of the material.
UIN (Unique Identifying Number)
The Unique Identifying Number (UIN) can also be called the Goods Inward Number, Lot Number, or Batch Number. This number is crucial because it allows for traceability and uniquely identifies each consignment. When a product is being formulated, the UIN is stored in the laboratory, on the computer, and in production.
The expiry date is the date that the goods can no longer be used. It is obvious that once goods expire, they should be thrown out and must not be used again.
Conditions for storage
If products and materials are not stored in approved storage conditions, they can become brittle. Final products must be stored in accordance with approved storage conditions.
A unique barcode is used by some companies to provide a second unique identifier of the product or material. This barcode can be used to electronically scan the item’s identity before it is issued.
Each lot must have an identification number. A status label is required for each lot to indicate the material’s status. Below are some examples of physical status labels. You will notice the use of different colors. (Note: Different companies might use different colors for different types of status labels)
You can choose to label your status with either:
- The container should have physical labels
- Electronic fields in a database
- Combination of electronic and physical
To ensure only authorized materials are used, it is important to be familiar with the company’s system.
Before any lot can be used in manufacturing it must be released to QC. Once a lot has passed inspection and testing, QC will change the status from “Hold”/”Quarantine” to “Released”/”Approved”.
This label is used for goods that have not been tested and released to the laboratory. Material labeled as Quarantine should be avoided.
Label for holding
The Hold label means that the material is being investigated and may be at risk. Under no circumstances, do not use.
Label for release
The material has been released to allow for its use. The Quality Department has cleared the batch.
The approval label signifies that the material can be used or released for sale. The laboratory has cleared the batch.
The label Rejected indicates that the batch was deemed unacceptable or defective. These materials should not be used. These materials should be kept in a separate, locked location
Product labels can be controlled
GMP is crucial in ensuring that product labels are properly controlled. Customers could be negatively affected by mislabeled products. Therefore, all product labels should be carefully controlled. These controls include:
- To prevent any mix-ups, each label type is clearly identified and separated in the label shop.
- Only authorized personnel can have access to the label store.
- The store should not have any loose labels or approved labels.
- All damaged or unused labels must be returned to Quality Department.
- Only the Quality Department should issue “Approved” and “Released” labels.
- To verify that the labels are released, they must first be double-checked against the original work order.
- Name and code of the product
- The version number and label identity
- Expiry date and coded batch number
- Only after all checks are completed satisfactorily can labels be placed in the packaging area.
GMP storage requirements in the warehouse
You must store components and materials that are considered to start in the right places.
Certain materials may require additional security and safety procedures. The following items must be secured against unauthorized access.
- Packaging materials printed
- High-potency drugs, such as antibiotics and drugs of addiction
- Poisons, flammable goods
- Material recalled and rejected
- Return goods
- Keep powders, liquids, corrosive, and flammable materials separated.
To prevent contamination and spills in dangerous goods areas, special equipment should be installed.
How to Keep Your Warehouse Clean
GMP regulations stipulate that warehouses storing components, raw materials, and finished goods must be kept dry, clean, and in order at all times.
This includes, but isn’t limited to:
- Protecting the receiving areas from the weather
- Regularly inspect containers and packages to make sure they are sealed correctly
- Regular cleaning of the facility
- Spills must be cleaned up immediately
- It is possible that the exterior of the inward goods containers will need to be cleaned prior to storage.
Protect goods from deterioration
- Keep goods at the temperature indicated on the labels.
- Monitor and alarm refrigerators and freezers.
- Monitoring temperatures in areas where goods require special storage conditions are important.
- Examine all documents and make any necessary changes.
- Examine all possible deviations and determine their impact on product suitability.
Protecting raw materials
Raw materials can deteriorate upon storage and become contaminated if they are not stored correctly. Proper storage conditions are crucial to ensure product purity. There are specific GMP rules that protect raw materials.
Separate reject and quarantine areas
- The storage environment should be temperature-controlled.
- Keep your goods away from the walls and off the floor.
- Use a system to identify material that is about to expire so it can be retested, if needed.
- Regularly inspect stockrooms for expired stock, cleanliness, cleaning, housekeeping, pest control, and past-expiry.
- To protect the environment, seal all containers that have been opened.
- You should ensure that each area of the warehouse is cleaned regularly, including external areas like gangways, shelves, and racking.
Pests that can be attracted to pharmaceutical warehouses include rats and mice, birds, ants, and cockroaches. For example, rodent droppings or bird droppings can cause contamination of stored goods. GMP rules stipulate that manufacturing facilities must have:
- The nominated pest control officer
- Specific instructions or agreements made with pest control companies
- Map showing the locations of bait
- Documentation of all pest-control treatments
- Regular waste collection
- Companies are required to ensure that employees and the environment are protected from pest control chemicals under OH&S and environmental regulations.
An effective pest control program involves:
- Between pest control company visits, keep track of any pest sightings
- Assigning someone to be with the pest control agent on-site
- Only use approved pesticides
- Controlling the air supply to the warehouse
The warehouse connects the outside environment with the inside production facility. The warehouse acts as a barrier against dirt, dust, particles and moisture from getting into the building.
Warehouses are designed to separate the production areas from the outside. Employees must keep doors closed whenever possible.
Outside air cannot be controlled. The factory can be left open and the wind can blow contaminants into it. It is therefore important to keep the outer door closed when not being used. The warehouse’s outer door is the first protection.
Here goods are unloaded from the delivery truck and inspected before being moved into the warehouse. This area is protected from dirt and dust by having an inner curtain and an outer roller door. It is important to keep the inner barrier and the outer roller door closed at the same time. This is often referred to as the “black” area.
This is where the outer bags and cartons are removed. You should not send goods into the warehouse if they are dirty or damaged.
Although the warehouse isn’t under pressure, it is much cleaner than the reception area. The warehouse should keep goods off the floor and away from walls. Moisture can be trapped between concrete walls and floors. This area is often referred to as the “grey” zone because it is cleaner than the outside but not enough to expose products.
Some companies refer to this area as a “white” (or “clean”) zone where only clean materials can be taken. Most goods are transported to this area on plastic pallets as wooden pallets can be difficult to clean and harbor mold, fungus, and bacteria. To prevent dirt and particles from entering, the production zone is controlled by pressure. It is important to keep the doors between production and warehouse areas shut to preserve positive pressure.
The outer cartons from the truck that arrived before materials were taken to the production area are usually removed. Many companies have different dress codes for moving from a grey to a white zone.
Controlling storage temperature is important
Temperature control is important in the warehouse to maintain product integrity throughout its shelf life. Exposure to extreme temperatures can cause damage to medicinal products and/or loss in therapeutic effects. It may not even be obvious.
For temperature-controlled warehouses, companies are expected to create a temperature map of the facility. This map will help to determine the best areas in which to store goods. This map is created by a preliminary study. It will show you where potential problems might be.
Following initial mapping, the temperatures are monitored daily or continuously on a routine basis. Monitoring may show seasonal patterns that could indicate temperatures rising or falling outside of approved limits. It is crucial to monitor temperature profiles in warehouses throughout the year, especially during winter and summer. Some companies use an electronic building management system to monitor their buildings.
Ambient temperature storage
Different companies and regulators have different meanings for the terms “room” and “ambient” temperature storage conditions. The term “temperate storage” is now more commonly used. Temperate storage is defined as storage temperatures between 15 and 30 degrees Celsius, with occasional exceptions.
Although temperature storage regulations vary from product-to-product, most licensed products have a maximum limit of 25°C. There is no lower limit than “protect from freezing” According to inspectors, temperate storage is allowed at temperatures between 8 and 15 degrees Celsius.
Additional requirements are required for temperature control
- It is important that the conditions of storage for goods be compatible with those conditions as specified on the labels.
- Temperature recording devices should be used to monitor controlled storage areas. All records must be reviewed, filed, and their results tabulated.
- Both an alarm and visual signal should be installed in the freezer and frozen storage areas. Only an authorized person can reset this signal.
- If temperatures are found to be outside of the recommended temperature for a prolonged period of time, contact the manufacturer to resolve the issue.
- To ensure accuracy, temperature monitoring equipment should be calibrated regularly.
How to make a temperature map
One simple example of temperature control is the location of material stored within the warehouse. If material is stored higher in the warehouse, it will heat up more. Therefore, goods that require cooling will not be placed near the ceiling.
- Analyse the temperature profile and find potential hot and cold areas.
- Use calibrated temperature monitoring instruments to identify areas at greatest risk.
- Develop a temperature mapping validation protocol.
- Based on your initial findings, you can begin monitoring on a regular schedule.
- Create a temperature map of your premises.
- Consider the hot and cold zones when temperatures outside are extreme.
- Check out the controls for heating and cooling systems.
- In the event that temperatures become compromised, ensure there is an action plan.
Cold storage is the storage of products that need to be kept at 2degC-8degC or when material must be frozen (e.g. Below -20degC and below -70degC
A successful cold storage operation requires that the facility selects the correct temperature recording instrumentation, validates its processes, and documents records and procedures. This includes responding to alarm conditions.
Instruments that are used in the warehouse
It is crucial to choose the right recording instrument. It is important that the instruments can be read easily and that data can be retrieved. The calibrated instruments should conform to national standards (the company should keep a copy of the calibration certificate), and an alarm for high/low temperatures should be included. Usually, max/min thermometers will not be accepted.
It is important to record both product and air temperatures. It is important to note that product temperature can fluctuate significantly more than air temperature (often called “load”) temperature.
Documentation and validation of temperature control
Validation efforts should:
- You can prove that temperature mapping is accurate for extreme temperatures.
- Check on temperature variations during use.
- Demonstrate your ability to perform in the face of power failures.
- Demonstrate alarm function.
There are specific procedures that must be followed:
- Temperature records are checked at the beginning of each day and recorded in a log.
What do you do if certain staff members are not available?
- A program should be established to review the cold storage controls as part of a self-inspection program. It should include a weekly and monthly review of cold store temperature records.