In the pharmaceutical industry, it is critical to pay attention to the storage and distribution of products. Medicines need to be stored under very specific conditions to ensure they retain their quality. Different dosage forms must be stored and transported under different environmental conditions and therefore, there cannot be one general rule for their handling. Thus, it is vital to follow good warehousing practice and good distribution practices to ensure the quality of products is maintained.
The WHO Guide to good storage practices for pharmaceuticals highlights the following important areas for the warehousing of pharmaceuticals.
Personnel
Table of Contents
All sites where pharmaceutical products are stored (manufacturing unit, distributor /wholesaler /retail sale pharmacy premises) must have a sufficient number of appropriately qualified and trained personnel. The staff must be given the necessary training on good storage practices, the best practices to adopt, and safety issues. They must also be trained on matters of personal hygiene, good sanitation practices, the use of working garments, and suitable protective clothing. Those employees who work in special storage areas (such as cold stores, for example) must be trained on the regulations and procedures particular to their work.
Premises and Facilities For Good Warehousing Practice
Storage areas
1. Entry: Entry into storage areas must be controlled, and only authorized persons must be permitted to enter.
2. Size: The areas must be of a size sufficient to allow the systematic storage of different categories of materials such as raw materials, packaging materials, intermediate products, bulk products, and finished products. There must be separate areas for products in quarantine, approved products, and products that have been rejected, returned, or recalled from the market.
3. Storage conditions: The storage areas must be designed to allow optimum storage conditions. They must be dry and clean at all times. Temperature and relative humidity must be maintained within the prescribed limits. There must be provisions to check, monitor, and record these parameters. All materials must be stored off the floor on racks or pallets, with sufficient space in between to permit easy cleaning as well as inspection if required. The pallets and racks must be kept clean and well[1]maintained.
4. Cleanliness: The storage areas should be cleaned regularly to avoid the accumulation of waste. Measures should be taken to prevent the entry of vermin. There must be written instructions available that indicate the cleaning methods to be adopted and the frequency of cleaning. Systems must be set up for pest control and written instructions provided. Agents used for pest control must be safe, and not cause any contamination of the materials being stored. Adequate measures must be taken to clean any product spillage, to avoid the risk of contaminating other products in the storage area.
5. External areas: Receiving and dispatch areas in the warehouse should be designed to protect materials from weather conditions. The design of receiving areas should be such as to allow cleaning of incoming materials before storage, if necessary.
6. Quarantine areas: Areas meant for storage of products in quarantine must be indicated, and be situated separately from the general storage areas. Entry into this area must be restricted to only those personnel who are authorized. Non-physical quarantine methods may be used (computerized systems, for example) provided they are validated to prove they provide a secure system equivalent to that of physical quarantine.
7. Sampling: Separate sampling area for starting materials must be provided in a controlled environment. When sampling is done in the storage area itself, care must be taken to prevent contamination of other products or cross-contamination. This area must be regularly cleaned.
8. Storage of rejected, expired, returned, or recalled materials or products: Separate areas must be provided for storing rejected, expired, returned, or recalled materials or products. Such materials must be conspicuously market to avoid inadvertent mix-ups. Physical segregation is best; non-physical systems (electronic) must be validated to prove they provide adequate levels of security.
9. Special materials storage: Pharmaceutical products that are sensitive, dangerous, hazardous, narcotic, radioactive, and/or highly active as well as substances with a risk of fire, explosion, or abuse must be stored in dedicated areas with sufficient security and safety measures in place.
10. Handling and distribution: All materials in the storage area must be handled, stored, and distributed in keeping with GMP guidelines. Procedures must be designed to prevent mix-ups, contamination, and cross-contamination. Storage conditions should ensure quality is maintained at all times.
11. Rotation of stock: All stocks in the warehouse must be rotated appropriately, following the “First Expired/First Out (FEFO)” principles.
12. Rejected materials: Products and materials that have been rejected must be marked and controlled with a quarantine system that prevents their use until their fate is decided. 13. Narcotic drugs storage: The storage of narcotic drugs must comply with international conventions as well as national laws regarding narcotics storage.
14. Damaged items: Damaged and broken items must be immediately removed from the usable stock and stored separately until their fate is decided.
15. Lighting: Storage areas must be lighted appropriately to allow the safe and accurate performance of all operations in the warehouse.
Storage Conditions For Good Warehousing Practice
All pharmaceutical materials and products must be stored in compliance with the requirements specified on the respective labels. These specifications must be based on the results obtained during the stability testing of the respective products. Storage conditions must be regularly monitored to ensure compliance with requirements. Recorded data (temperature, relative humidity, etc.) must be available if required for review. Data monitoring and recording equipment must be checked and calibrated at predetermined intervals; results of these checks must be recorded and maintained for a duration of shelf life of the product plus one year, or as specified in the national regulations. Monitoring equipment must be located in those areas which are most likely to experience fluctuations; this equipment must be regularly calibrated.
Storage Requirements For Good Warehousing Practice
Documentation
1. Instructions and records: Written instructions, as well as records, must be available to document all activities taking place in the storage area, including those related to expired stock handling. The route taken by the products and information through the organization in case of product recall must be described in sufficient detail.
2. Information of each product: Each material or product stored must have permanent information (in either written or electronic form) to provide information regarding the storage conditions, precautions if any to be observed, and dates for re-test. Labels must be in keeping with requirements as per the respective pharmacopeias and current national regulations.
3. Delivery records: Records must be maintained for every delivery, and must include information regarding the description of the goods, quantity, quality, supplier and the batch number, receipt date, assigned batch number, and expiry date. These records must be retained for a duration equal to the shelf life of the goods plus one year or as specified in the national regulations.
4. Comprehensive records: All details regarding the materials and pharmaceutical products received and issued in the warehouse must be recorded and maintained by a specific system to permit their identification such as by batch number.
Labeling and Containers
1. Storage containers: Pharmaceutical products and all materials must be stored in appropriate containers so that their quality is not affected. The containers must provide sufficient protection from external factors such as bacterial contamination.
2. Container labeling: The minimum labeling requirements for containers include details of – name of the material with pharmacopoeial reference where applicable (proper name only, no code names or abbreviations can be used without authorization), batch number, expiry date, re-test date, and storage conditions to be maintained.
Receiving Incoming Materials
1. Verification: Every incoming delivery must be checked immediately against the details given in the purchase order. All containers must be physically verified by the description on the label, type of material, batch number, and quantity.
2. Uniformity: The uniformity of the containers must be verified. Further subdivision may be done in keeping with the supplier’s batch number in cases where the delivery contains more than a single batch of products.
3. Inspection: Every container must be carefully checked for any contamination, damage, or tampering. If the inspection reveals evidence of such an incident, the entire consignment must be kept under quarantine until further investigation.
4. Sampling: Sampling should be done only by authorized personnel who are adequately qualified and trained, in keeping with written instructions for sampling. Labels must be affixed on the containers from which samples have been drawn.
5. Quarantine: Goods must be stored under quarantine after sampling until authorized release or rejection instructions are obtained. Separate batches must be stored segregated from each other.
6. Rejected materials: Rejected materials must be stored segregated from other products to prevent their accidental use. Appropriate measures must be taken to either return them to the supplier or to destroy them if deemed necessary.
Warning signs of problems with incoming materials:
1. Odors: May indicate spillage of product. In some cases, may indicate interactions of cleaning agent/preservative with the drug product.
2. Moisture/fluid: Evidence of damage in packaging that has caused the drug to leak. May also warn of premises being exposed to moisture/the elements.
3. Spillage: Medicines lose from their original container indicate damage to the package. In some cases, it renders the product unsafe and unfit for use.
4. Dirt, tears, scratches, animal feces: Indicate activity of pests such as rodents that have used the shipping material for a shelter. The safety of the drugs may be compromised because these pests may carry diseases too.
5. Damaged/tampered temperature tags: Tags are used to record temperature conditions under which shipping was done for thermolabile products. Damaged/ tampered tags indicate deviations from the required temperature, which may have rendered the product unsafe for use.
Stock Rotation and Control
Periodically, the actual stock in the warehouse must be compared with the recorded quantity of stocks. If such reconciliation reveals discrepancies, they must be investigated to find out if the material has been incorrectly issued or if there has been a mix-up. Containers that have been partly used must be closed and sealed securely to prevent contamination and spoilage. Previously opened or partly used containers must be used up before fresh containers are opened. Containers that have been damaged must not be issued unless tests have shown that the quality of the product is unaffected by the damage.
Control of Obsolete and Outdated Products
Stock in the warehouse must be periodically checked and expired/obsolete/outdated products and materials must be removed. Until such material is removed, precautions must be taken to ensure they are not issued for use.
Returned Goods
Goods whether returned or recalled from the market must be handled according to approved procedures. Records of the same should be maintained. All such goods must be kept in quarantine until a decision has been taken by the nominated, responsible person. Goods that pass a quality re-evaluation may be returned to stock approved for sale. Records of such events must be maintained in the stock records. Any pharmaceutical product returned by patients to the pharmacy must be destroyed.
Dispatch and Transportation of Goods
The dispatch and transport of pharmaceutical products must be done under conditions that ensure the prescribed storage conditions are maintained, and the integrity of the product is not affected. When dry ice is used, care must be taken to ensure it does not come into contact with the product as it may cause freezing of the product. When the material is being transported, devices must be used to monitor temperature conditions; records of such monitoring must be maintained.
Any transportation must proceed only on receiving a delivery order. Documents must be maintained showing the delivery order and dispatch details. External containers must be clearly labeled in indelible ink and must provide adequate protection to the product from weather conditions. Dispatch records must contain the following details at the very minimum – dispatch date, customer name and address, product description (name, strength, dosage form), quantity, batch number, storage conditions.
Product Recall
Appropriate procedures must be set in place for prompt and effective market recalls of known or suspected defective products. Product recalls may be triggered by any of the following situations:
- Customer complaints that draw attention to a critical quality defect.
- Reports of adverse drug reactions.
- Samples retained for stability studies show deterioration of product quality.
- GMP deviations uncovered during regulatory inspections.
- Information becomes available indicating that counterfeit or tampered product has been supplied in place of authentic drug.
Case Study of Tylenol
In 2010, McNeil Consumer Healthcare, a division of Johnson and Johnson, announced a recall of extra-strength Tylenol, Tylenol grape meltaway tablets, Tylenol rapid release gel caps, and some other products due to complaints of a musty, moldy smell and black particles. Similar complaints had been received even in 2008 and 2009, leading to the recall of some lots of their products. Some patients complained of not just the smell but also nausea, vomiting, stomach pain, and diarrhea. Post these events, an investigation was conducted by the company, and the results showed the odor to be caused due to traces of a chemical named 2,4,6-tribromoanisole (TBA). This chemical was used as a preservative on wooden pallets that were employed in the storing and transporting of the Tylenol product plastic bottles.
Once finished products reach the warehouse, they are not subjected to any further testing or inspection. If products undergo deterioration or damage at this stage, they may go unnoticed, and a harmful product may find its way to the patient. It is therefore vital that good warehousing practices must be followed by adequately trained personnel to make sure that the quality of the product reaching the end-user is the same as it was when it left the manufacturing unit.
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