Materials in Pharmaceutical as per WHO Guideline
Principle.
The main objective of a pharmaceutical plant is to produce finished products for patients’ use from a combination of materials (starting and packaging).
Materials include starting materials, packaging materials, gases, solvents, process aids, reagents and labelling materials.
No materials used for operations such as cleaning, lubrication of equipment and pest control should come into direct contact with the product. Where possible, such materials should be of a suitable grade (e.g. food grade) to minimize health risks.
All incoming materials and finished products should be quarantined immediately after receipt or processing, until they are released for use or distribution.
All materials and products should be stored under the appropriate conditions established by the manufacturer, and in an orderly fashion, to permit batch segregation and stock rotation by a first-expire, first-out rule.
Water used in the manufacture of pharmaceutical products should be suitable for its intended use.
Starting materials
The purchase of starting materials is an important operation that should involve staff who have a particular and thorough knowledge of the products and suppliers.
Starting materials should be purchased only from approved suppliers and where possible, directly from the producer. It is also recommended that the specifications established by the manufacturer for the starting materials
be discussed with the suppliers. It is beneficial for all critical aspects of the production and control of the starting material in question, including handling, labelling and packaging requirements as well as complaints and
rejection procedures, to be contractually agreed between the manufacturer and the supplier.
For each consignment, at a minimum, the containers should be checked at least for integrity of package and seal and for correspondence between the order, the delivery note, and the supplier’s labels.
All incoming materials should be checked to ensure that the consignment corresponds to the order. Containers should be cleaned where necessary and labelled, if required, with the prescribed information. Where additional
labels are attached to containers, the original information should not be lost.
Damage to containers and any other problem that might adversely affect the quality of a material should be recorded and reported to the QC department and investigated.
If one delivery of material is made up of different batches, each batch must be considered as separate for sampling, testing and release.
Starting materials in the storage area should be appropriately labelled. Labels should bear at least the following information:
(a) the designated name of the product and the internal code reference where applicable;
(b) the batch number given by the supplier and, on receipt, the control or batch number given by the manufacturer, if any, documented so as to ensure traceability;
(c) the status of the contents (e.g. in quarantine, on test, released, rejected, returned, recalled);
(d) where appropriate, an expiry date or a date beyond which retesting is necessary. When fully validated computerized storage systems are used, not all of the above information need be in a legible form on the label.
There should be appropriate procedures or measures to ensure the identity of the contents of each container of starting material. Bulk containers from which samples have been drawn should be identified.
Only starting materials released by the QC department and within their shelf-life should be used.
Starting materials should be dispensed only by designated persons, following a written procedure, to ensure that the correct materials are accurately weighed or measured into clean and properly labelled containers.
Each dispensed material and its weight or volume should be independently checked and the check recorded.
Materials dispensed for each batch of the final product should be kept together and conspicuously labelled as such.
Packaging materials
The purchase, handling and control of primary and printed packaging materials should be as for starting materials.
Particular attention should be paid to printed packaging materials. They should be stored in secure conditions so as to exclude the possibility of unauthorized access. Roll feed labels should be used wherever possible. Cut labels and other loose printed materials should be stored and transported in separate closed containers so as to avoid mix ups. Packaging materials should be issued for use only by designated personnel following an approved and documented procedure.
Each delivery or batch of printed or primary packaging material should be given a specific reference number or identification mark.
Outdated or obsolete primary packaging material or printed packaging material should be destroyed and its disposal recorded.
All products and packaging materials to be used should be checked on delivery to the packaging department for quantity, identity and conformity with the packaging instructions.
Intermediate and bulk products
Intermediate and bulk products should be kept under appropriate conditions.
Intermediate and bulk products purchased as such should be handled on receipt as though they were starting materials.
Finished products
Finished products should be held in quarantine until their final release, after which they should be stored as usable stock under conditions established by the manufacturer.
The evaluation of finished products and the documentation necessary for release of a product for sale.
Rejected, recovered, reprocessed and reworked materials
Rejected materials and products should be clearly marked as such and stored separately in restricted areas. They should either be returned to the suppliers or, where appropriate, reprocessed or destroyed in a timely manner. Whatever action is taken should be approved by authorized personnel and recorded.
The reworking or recovery of rejected products should be exceptional. It is permitted only if the quality of the final product is not affected, if the specifications are met, and if it is done in accordance with a defined and authorized procedure after evaluation of the risks involved. A record should be kept of the reworking or recovery. A reworked batch should be given a new batch number.
The introduction of all or part of earlier batches, conforming to the required quality standards, into a batch of the same product at a defined stage of manufacture should be authorized beforehand. This recovery should be carried out in accordance with a defined procedure after evaluation of the risks involved, including any possible effect on shelf-life.
The recovery should be recorded.
The need for additional testing of any finished product that has been reprocessed, reworked or into which a recovered product has been incorporated, should be considered by the QC department.
Recalled products
Recalled products should be identified and stored separately in a secure area until a decision is taken on their fate. This decision should be made as soon as possible.
Returned goods
Products returned from the market should be destroyed unless it is certain that their quality is satisfactory; in such cases they may be considered for resale or relabeling, or alternative action taken only after they have been critically assessed by the QC function in accordance with a written procedure. The nature of the product, any special storage conditions it requires, its condition and history, and the time elapsed since it was issued should all be taken into account in this assessment. Where any doubt arises over the quality of the product, it should not be considered suitable for reissue or reuse. Any action taken should be appropriately recorded.
Reagents and culture media
There should be records for the receipt and preparation of reagents and culture media.
Reagents made up in the laboratory should be prepared according to written procedures and appropriately labelled. The label should indicate the concentration, standardization factor, shelf-life, the date when restandardization is due, and the storage conditions.
The label should be signed and dated by the person preparing the reagent.
Both positive and negative controls should be applied to verify the suitability of culture media each time they are prepared and used. The size of the inoculum used in positive controls should be appropriate to the sensitivity required.
Reference standards
Whenever official reference standards exist, these should preferably be used.
Official reference standards should be used only for the purpose described in the appropriate monograph.
Reference standards prepared by the producer should be tested, released and stored in the same way as official standards. They should be kept under the responsibility of a designated person in a secure area.
Secondary or working standards may be established by the application of appropriate tests and checks at regular intervals to ensure standardization.
Reference standards should be properly labelled with at least the following information:
(a) Name of the material;
(b) batch or lot number and control number;
(c) date of preparation;
(d) shelf-life;
(e) potency;
(f) storage conditions.
All in-house reference standards should be standardized against an official reference standard, when available, initially and at regular intervals thereafter.
All reference standards should be stored and used in a manner that will not adversely affect their quality.
Waste materials
Provision should be made for the proper and safe storage of waste materials awaiting disposal. Toxic substances and flammable materials should be stored in suitably designed, separate, enclosed cupboards, as required by national legislation.
Waste material should not be allowed to accumulate. It should be collected in suitable receptacles for removal to collection points outside the buildings and disposed of safely and in a sanitary manner at regular and frequent intervals.
Miscellaneous
Rodenticides, insecticides, fumigating agents and sanitizing materials should not be permitted to contaminate equipment, starting materials,packaging materials, in-process materials or finished products.
