1. Purpose
The purpose of this Guideline is to provide guidance on the warehousing and distribution of commercial products.
2. Scope and Applicability
This Guideline is applicable to:
– All products, including intermediates, active pharmaceutical ingredients, bulk formulated and finished products
– All commercial manufacturing sites and marketing companies, its licensees, joint-ventures and contractors
3. Definitions
3.1 Active Pharmaceutical Ingredient
Any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product that when used in the production of a drug becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease or to affect the structure and function of the body.
3.2 Intermediate
Material produced during manufacture that undergoes further change or purification. Intermediates may or may not be isolated.
3.3 Bulk Formulated Product
A pharmaceutical product (Formulated Drug/Formulated Product) held in large intermediateor shipping containers and ready to be filled into primary containers.
3.4 Finished Product
A product which is packaged and labeled for supply to a wholesaler, hospital, pharmacy, doctor or patient.
3.5 Storage Life Management System
The global electronic documentation management system used by Operations and Pharmaceutical Analytical R&D, containing information on shelf lives and storage conditions for both commercial products and products used in clinical trials.
4. Responsibilities
4.1 It is the responsibility of each business unit accountable for warehousing and distribution of materials listed in section 2, to put in place procedures that describe the controls required to ensure the quality and integrity of product during warehousing and distribution.
4.2 It is the responsibility of each business unit accountable for warehousing and distribution to put in place procedures that describe the process for management control and audit of external warehouses and distributors.
4.3 It is the responsibility of the unit conducting the audits of the joint-ventures, licensees and contractors to make sure that this International Guideline is adhered to.
4.4 It is the responsibility of R&D management to ensure that the relevant information regarding product storage conditions are established. This information should be forwarded to Dossier Management Team, Supply Chain, who enter into the Storage Life Management System (S-Life).
5. Guideline
5.1 Personnel
5.1.1 A representative should be appointed in each warehouse and distribution point, who should have defined authority and responsibility for ensuring that a quality system is implemented and maintained.
5.1.2 Key personnel involved in the warehousing of products should have the appropriate ability and experience to guarantee that the products are properly stored and handled.
5.1.3 Personnel should be trained in relation to the duties assigned to them and the training sessions should be recorded.
5.2 Documentation
5.2.1 Written procedures should describe the different warehousing and distribution operations, including:
* Cleaning and maintenance of the premises (including pest control)
* Receipt and checking of the deliveries
* Storage, including monitoring and where necessary control of the storage
* Conditions
* Transportation conditions
* Stock security on site and in transit
* Withdrawal of stock from saleable distribution
* Records, including records of orders & distribution
* Handling of returned and recalled products.
* Management of personnel (including training)
* Management of product shipped ahead of clearance
These procedures should be approved, signed and dated by the person responsible for the quality system.
5.2.2 Records should be kept of each despatch/receipt transaction, showing the following information:
* Date/time of dispatch/receipt
* Name of the product including strength
* Package size
* Quantity
* Batch number
* Name and address of customer/supplier
* Article number or similar
5.2.3 Records should be made at the time each operation is undertaken and in such a way that all significant activities or events are traceable. Records should be clear and readily available. They should be retained for shelf life plus one year or at least five years, whichever is the longer. Local legislative and regulatory requirements with respect to time the documents should be retained, take precedence over this Guideline, so long as the minimum requirements stated above are met.
5.3 Warehousing Premises and Equipment
5.3.1 Premises and equipment should be suitable and adequate to ensure proper storage and distribution of products. Any special storage requirements shall be met.
5.3.2 The storage facilities should be clean and free of litter, dust and pests. A pest control program should be implemented.
5.3.3 Adequate precautions should be taken against spillage or breakage, attack and contamination by micro-organisms or other products. Materials and equipment necessary to contain and clean-up spills should be readily available.
5.3.4 Receiving and dispatch bays should protect products from the weather. The reception area should be separate from the storage area. Reception areas should be designed and equipped to allow containers of incoming materials to be cleaned where necessary before storage. Deliveries should be examined at receipt in order to check that containers are not damaged and that the consignment corresponds to the order.
5.3.5 Products should be stored in an orderly manner to allow batch segregation. There should be only one batch of a product placed on a pallet. Products should not be stored directly on the floor unless held on a suitable pallet.
5.3.6 Stocks of different quality status (e.g. quarantine, released, on hold, rejected) should be segregated by appropriate means e.g. physical segregation or segregation by control of systems using a validated computer system.
5.3.7 Recalled and returned goods should be identified as such and stored in a physically segregated area.
5.3.8 Special precautions should be taken for the storage of hazardous, sensitive and dangerous materials. Narcotic drugs should be stored in compliance with national and international law regulations on narcotics.
5.3.9 Penicillin and beta-lactam materials should be physically isolated from other stock, in a dedicated facility with a dedicated air-handling system and proper control of personnel.
5.3.10 Physician samples or registration samples should normally be stored apart from other goods and under the conditions specified by the manufacturer in order to avoid any deterioration.
5.3.11 Storage temperature should be monitored with calibrated devices and recorded at a defined frequency. The records should be reviewed regularly. Temperature limits should be set based upon the requirements of the product being stored.
5.3.12 If required, humidity should also be monitored with calibrated device and recorded at a defined frequency. The records should be reviewed regularly and the humidity limits should be set based upon the requirements of the product being stored.
5.3.13 When specific temperature and humidity storage conditions are required, storage areas should be equipped with temperature and humidity recorders or other devices that will indicate when the specific temperature and humidity range has not been maintained (e.g. alarm system). Control should be adequate to maintain all parts of the relevant storage area within the specified temperature and humidity range.
Procedures should define how to react to a temperature and/or humidity excursion.
5.3.14 There should be a system to ensure stock rotation to ensure that material with the earliest expiry date is used first with regular and frequent checks that the system is operating correctly. If any exceptions to this are made the reasons should be recorded.
5.3.15 Products near or beyond expiry date or shelf life should be segregated by appropriate means e.g. physical segregation or segregation by control of systems using a validated computer system.
5.3.16 Products with broken seals, damaged packaging, or suspected of possible contamination should be kept in a clearly separated area or clearly labeled so that they cannot be used, be dispatched in error or contaminate other goods.
5.4 Transportation and Distribution
5.4.1 Products should only be distributed to authorized wholesalers or to other units authorized to receive/supply product. This may include sales representatives responsible for finished product distribution.
5.4.2 company units, its licensees, joint-ventures and contractors should engage haulage contractors to distribute the products in such a way that:
* Product identification is maintained.
* Products do not contaminate, and are not contaminated by, other products or materials.
* Adequate precautions are taken against spillage, breakage, theft or tampering.
* Products are secure and not exposed to unacceptable degrees of heat, cold, light, moisture or other adverse influence, nor to attack by micro-organisms or pests.
5.4.3 Products requiring controlled temperature storage should also be transported by appropriately specialized means and a temperature monitoring device should accompany each delivery.
5.4.5 APIs, intermediates, bulk tablets/capsules being transported between own sites/functions or being received from contractors/vendors will be sealed properly.
5.5 Distribution under Quarantine
Manufacturing units may need to distribute products under quarantine status to another own unit using the time in transit for Quality Assurance/Quality Control testing. This should be carried out in accordance with proper procedure.
5.6 Customer Returns
5.6.1 Customer returns should be handled according to appropriate procedure.
5.6.2 Non-defective finished product, which has been returned, should be separated from saleable stock to prevent redistribution until a decision has been reached regarding their disposal, or recovery.
5.6.3 Finished product, which has left the care of the wholesaler, should only be returned to saleable stock if it meets the proper requirements.
5.6.4 Records of returns should be kept. The responsible person should formally release goods suitable for return to saleable stock. Products returned to saleable stock should be located such that distribution of stock based on expiry date is upheld.
5.7 Recalls
5.7.1 An emergency plan for recalls should be described in writing.
5.7.2 Recall operations should be recorded at the time they are carried out. If requested these records should be made available to the competent authorities in whose territory the products were distributed.
5.7.3 In order to ensure the efficacy of the emergency plan, the full distribution records for finished products should be readily available.
5.7.4 In the case of a recall, the level of recall will be determined as part of the recall strategy. It is the decision of the distribution unit as to whether a wholesaler is to contact their customers. If yes, the wholesaler may decide to contact all of their customers or only those having received the batch to be recalled. Contact should be made within the specified timescales.
5.8 Suspect Counterfeit or Counterfeit Products
Suspect counterfeit products found in the distribution network should be clearly labeled and kept apart from other products to avoid any confusion.
5.9 Disposal of Rejected, Returned, Recalled or Counterfeit Product
A formal decision should be taken on the disposal of these products and the decision should be recorded. The person responsible for the quality system of the wholesaler and, where relevant, local QA manager should be involved in the decision making process.
5.10 Self Inspections
Self-inspections should be conducted (and recorded) in order to monitor the implementation of and compliance with this guideline.