1. Purpose
The purpose of this Guideline is to describe the receipt, handling and storage of starting materials and packaging materials. The handling also includes sampling.
2. Scope and Applicability
This Guideline is applicable to all manufacturing units, its joint ventures, licensees and contractors performing manufacturing, packaging and repacking including labeling and change of leaflets.
3. Definitions
3.1 Starting Materials
Any material used in the production of an API, intermediate or a formulated product, but excluding packaging material
3.2 Packaging Materials
Any material employed in the packaging of a medicinal product, excluding any outer packaging used for transportation or shipment. Packaging materials are referred to as primary or secondary according to whether or not they are intended to be in direct contact with the product.
3.3 Printed Packaging Materials
Printed packaging materials are printed and/or otherwise decorated. In the case of printed packaging components for finished products, the text, and in some cases the decoration, forms a part of the legal labeling and design of the finished products, (e.g. labels, leaflets, pre-printed ampoules, tubes, foils).
4. Responsibilities
4.1 It is the responsibility of each site to have a written procedure, which describes the process for the receipt, handling and storage of starting materials and packaging materials.
4.2 It is the responsibility of the unit conducting the audits of the joint ventures, licensees and contractors to ensure that this International Guideline is adhered to.
5. Guideline
5.1 General Aspects
5.1.1 Receiving and dispatch bays should protect materials and products from the weather. Reception areas should be designed and equipped to allow containers of incoming materials to be cleaned where necessary before storage.
5.1.2 Suitable conditions for storing and sampling of starting materials and packaging materials shall be provided. Any special storage requirements as demanded by specifications should be met.
5.1.3 Handling and storage systems shall be designed to prevent contamination and mix-ups among materials of different code numbers and different batches.
5.1.4 Labels, leaflet, cartons and primary printed packaging materials (e.g. pre- printed ampoules, tube foils) shall be stored within a secured area. Other printed packaging materials should be stored under special attention. Admittance to stores for printed packaging materials should be allowed only by permission of the store personnel.
5.2 Receipt
5.2.1 Upon receipt, each consignment shall be identified against relevant documents such as purchasing order and delivery note and be examined for damage and cleanliness.
5.2.2 Any doubt about identity and any damage likely to affect the integrity or quality of the content and any suspected contamination shall be reported to Quality Assurance/Quality Control.
5.2.3 Damaged containers or containers which cannot be properly cleaned should either be rejected and immediately labeled as such or be stored under quarantine as waiting instructions from Quality Assurance/Quality Control.
5.2.4 The date of receipt, supplier, supplier’s batch number, quantity and number of containers should be recorded on relevant documents together with the standard name, code number and control number.
5.3 Identity
5.3.1 Each starting material and packaging material shall be identified with a standard name and a code number. For printed packaging material the code number shall be changed whenever the printed text is revised.
5.3.2 Apart from the code number, printed packaging materials, should have additional means for identity checks, e.g. bar codes for electronic code readers or for a visual identity check.
5.3.3 For identification of each batch of starting materials and packaging materials a control number, e.g. a Received Goods Number or a QC Number, should be assigned to each batch at receipt.
5.3.4 If a consignment of a given material consists of more than one batch from the supplier, each batch should be given a separate control number and handled as a separate batch.
5.4 Internal Labeling
5.4.1 Each container (or grouping of containers if transported as a unit in order not to lose identity) of starting materials and packaging materials should be adequately identified by an internal label upon receipt and during handling and storage.
5.4.2 To minimize the risk for transcription errors the labels should be multiplied or copied from a master by means of a validated system.
5.4.3 The labels for the starting materials shall bear at least the following information:
– The designated name of the product and the internal code reference where applicable.
– a batch number given at receipt
– where appropriate, a storage condition and an expiry date or a date beyond which retesting is necessary.
– When fully computerized storage systems are used, all the above information need not necessarily be in a legible form on the label.
– Where possible these labels should be applied adjacent to the supplier label.
5.4.4 The status of the material shall be indicated by different colours on the internal labels and by the corresponding text, e.g. yellow/”Quarantine”, green /“Released” and red/”Rejected”. If a fully computerized storage system is used a status indication on the internal label is not required.
5.4.5 Care must be taken that only one status is indicated on a container. This can be achieved by sticking the “Released” or “Rejected” label next to the “Quarantine” label, which should be crossed over. The labeling system should permit a check of identity on “Quarantine” label against the identity on “Released” or “Rejected” label to ensure that the right container is released or rejected. All labels should be stuck on the container body, not on the lid. An individual assigned this responsibility and based on written instructions should perform the labeling operation.
5.5 Sampling
5.5.1 Each batch of starting material and packaging material shall be sampled according to established sampling plans that take into account the criticality of the material, material variability, past quality history of the supplier and the quantity needed for analysis.
5.5.2 If the supplier samples the material, the sampling should be performed according to an agreed sampling instruction.
5.5.3 Sampling shall be performed by personnel and by methods approved by Quality Assurance/Quality Control under conditions and with a technique that will give a representative sample and preserve the initial quality of sample and sampled material with regard to microbiological, physical and chemical aspects. The sampling method should specify the number of containers to be sampled, which part of the container to sample and the sample size. Reference samples shall be taken.
5.5.4 Sample containers shall be identified with standard name, code number and control number. It should be possible to identify the person responsible for each sampling operation, the source of the sample and the date of sampling.
5.5.5 Containers from which samples have been taken should be marked to indicate that a sample has been taken. For example; with the persons signature and the sampling date. This will aid any supplementary investigation.
5.6 Quarantine
5.6.1 Quality Assurance/Quality Control shall hold starting materials and packaging materials under quarantine before release. Unprinted secondary packaging materials may be exempted.
5.6.2 Quarantine shall be achieved by either physical quarantine system or by a fully computerized storage system.
5.6.3 If a physical quarantine system is used the materials should be stored in areas designed for this purpose.
5.6.4 If a fully computerized system is applied there is no need for a segregated quarantine area. The system should be designed so that materials are not available for requisition before release. To achieve the necessary guarantee that only released materials are used for processing, the fully computerized system should be properly validated.
5.7 Evaluation and Release
All deliveries of starting materials and packaging materials should be tested, evaluated and released by Quality Assurance/Quality Control as appropriate.
5.8 Return of Materials
A material must be returned to stores only if name, code number and control number identify it and if the integrity of the material during handling is ensured. For starting materials and printed packaging materials the returned quantity should be recorded. Excess of printed packaging materials bearing batch numbers or other batch specific printing must be destroyed in connection with the line clearance procedure.
5.9 Rejected Materials
Rejected materials shall be clearly labeled as such and should be moved to the area allocated for rejects as soon as possible and should be disposed of without delay.
5.10 Inventory Record
There should be an inventory record for each batch of starting materials and printed packaging materials. The inventory record should contain sufficient information to allow reconciliation of the use of each batch of materials. All batches of finished products in which a certain material batch has been used should be identified. The system shall support first in-first out use of components, containers and closures.