Pharmaceutical Materials Management Chapter 3 PDF

Materials Management Introduction The prime objective of the pharmaceutical manufacturing operations is to produce finished pharmaceutical products from active, inactive raw materials and various packaging materials. The quality of finished products solely depends upon the quality inputs...

Materials Management Introduction The prime objective of the pharmaceutical manufacturing operations is to produce finished pharmaceutical products from active, inactive raw materials and various packaging materials. The quality of finished products solely depends upon the quality inputs and hence materials management becomes a very important activity in pharmaceutical manufacturing operations. The total materials management activity starts right from selection of vendors for raw materials (RM) and packaging materials (PM) to dispatch of finished products to its destination. Introduction All incoming materials should be quarantined immediately after receipt or processing, until they are released for use or distribution. Each container or grouping of containers of RM/PM shall be clearly identified with proper labelling for each lot in each shipment received. The labels should clearly define the status e.g. quarantined, approved or rejected etc. Introduction All materials and products should be stored under appropriate conditions, established by the manufacturer, and/or user. All these items should be handled all the time in such a fashion that no contamination or mix-up can take place. Bagged or boxed materials should be stored off the floor (on non- wooden pallets) and be suitably placed to permit cleaning and inspection. Introduction These should be stored in an orderly fashion to permit batch segregation and stock rotation by First In - First Out (FIFO) and First Expiry - First Out (FEFO) rule. There shall be written procedures for all activities carried out related to materials handling e.g. receipts, identification, storage, handling, sampling, testing and approval or rejection and RM/PM. Purchasing Regarding purchasing of pharmaceutical materials following points should be considered: (i) All materials should be purchased according to an approved and adequate specification: Specifications define not only the grade and quality of the materials, but also the nature of the packaging and container to be used. The quality material, should clearly specify the:  physical, chemical and microbiological specifications as specified in pharmacopoeial specifications or in-house specifications.  characteristics like, bulk density, particle size, amorphous or crystalline nature of the material, specificity of isomers etc. Purchasing (ii) Materials should be purchased and sourced only from approved suppliers (vendors) and manufacturers. Choice of vendor should be primarily based on quality considerations. When quality considerations are met other commercial consideration should play their role, like, price, delivery period. Consistency in quality, delivery and price should be given importance. Purchasing (iii) RM and PM should only be purchased by buyers who are trained and who possess sufficient technical knowledge. Materials managers who has sufficient exposure on RM/PM for pharmaceuticals should be appropriate persons for this; alternatively industrial pharmacists with training in materials management can do a much better job. Purchasing Vendor Certification The following points should be considered for vendor certification (They are usually covered in a related SOP) : (i) Selection of materials for certification. This may be based on criticality of the material and also on the commercial aspects. (ii) Selection of vendors for above selected materials. This may be based on the following issues:  Past history of the supplies made by him.  Trend of quality of materials.  Commitment to quality and delivery dates.  Compliance of quality parameters at his manufacturing site.  Compliance to overall quality systems etc.  Pricing and other commercial terms. Purchasing Vendor Certification (iii) Formation of a vendor certification team. This may be constituted from experts from various departments like – quality control, quality assurance, production, product development, engineering, finance and purchase etc. (iv) In the initial contact with the supplier/ manufacturer, the following process components should be studied e.g.  Study of the suppliers manufacturing process.  Product specification and evaluation.  Process evaluation.  Process and specification changes and change control system compliance.  Formal communication from supplier/ manufacturer on changes incorporated in process and specifications (even physical parameter specification like color, particle size, bulk density may affect the quality of finished product, and hence need to be communicated.) Purchasing Vendor Certification (v) A formal technical audit report of vendor should be carried out and formally reported to the management. (vi) Based on the audit findings vendors can be certified or de- certified. Raw Materials  Received RM: Supplier/Manufacturer of the received material should have his name listed in companies approved vendors list. Such list should be available with the receiving department. All received materials should be checked for following information, after receiving: (a) Name of the manufacturer/supplier. (b) Name of the product. (c) Batch numbers (d) Date of manufacture and date of expiry. (e) Quantity received and number of containers or packages. (f) Condition of containers and materials. The materials received should be taken into account only after all the relevant documents are available. (e.g. bills, invoice, customs or excise gate passes, certificate of analysis etc.). Raw Materials  Received RM: All received materials should be quarantined immediately after receipt until being sampled, tested and released (or any other decision e.g. rejected). All containers should be cleaned externally, and damages if any should be informed to QC department. The cleaned containers should be protected from contamination during storage. Raw Materials  Sampling: Sampling of these received materials should take place in specific sampling booths (cubicles) by QC persons only and containers should be labelled accordingly. These materials shall be stored in sampled material quarantine. Containers from which samples have been taken out should be identified. Containers from which partial material is issued should also be identified by a label indicating the various withdrawals from this and present quantity in the same at any moment of time. Generally, more than one container should not be with partially issued material.  Raw Materials  Dispensed materials: 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 container. The word correct material in above paragraph refers to the following points: (a) Correct name and category (B.P./U.S.P. etc.) of the material. (b) Correct analytical reference (AR) No. (c) Correct weight/measure. (d) Correct Batch No. of the product. Raw Materials  Dispensed materials: All dispensed materials must be recorded in a register in chronological order of date and time. This record should have at least the following information: (a) Name of the product and B. No. for which the material is dispensed. (b) Time and Date of starting and completion of the dispensing activity. (c) Name of the weigher and checker of the dispensed materials. Normally a QC person should check the weights independently. The production supervisor will check it at the time of processing the batch. Raw Materials SOP on dispensing of materials: This SOP should cover at least the following points: (i) Persons authorized to requisition the material and dispense and issue the materials. (ii) Precautions before dispensing the materials e.g.  Verification of balance for calibration.  Verification of environmental conditions e.g. temperature, humidity, class of air etc.  Verification of cleanliness and sanitary conditions of the utensils and area.  Proper uniform of the people.  Working of reverse laminar Air Flow Unit.  Availability of correct materials in required quantities. Raw Materials SOP on dispensing of materials: (iii) Precautions during dispensing of materials e.g.  Verification of each item during weighing.  Recording correct weight/volumes of materials.  Affixing proper labels.  Opening and closing the material containers properly.  Filling the dispensing documents correctly and fully and immediately.  Batch wise storing the dispensed materials securely; may be lockable stainless steel containers.  Getting the dispensed materials verified by a second person e.g. from QC/production etc. Raw Materials SOP on dispensing of materials: (iv) Precautions after dispensing of materials e.g.  Segregating the dispensed materials properly.  Returning the remaining materials to store in properly closed/ sealed conditions.  Cleaning the area and utensils used for dispensing. Packaging Materials Packaging materials are divided into following categories: (1) Primary Packaging Materials: Materials which come in direct contact with the medicinal product. e.g. bottles, ampoules, vials, foils etc. (2) Secondary Packaging Materials: Materials which come in contact with the primary packaging materials, e.g. labels, carton etc. (3) Printed Packaging Materials: All packaging materials which have any thing printed on it. Such materials include, labels, cartons, foils etc. (4) Tertiary and other Packaging Materials: All other packaging materials other than those covered in the above three categories. Packaging Materials While handling all these materials following points should be kept in mind. (i) The purchase, handling and control of primary and printed packaging materials shall be as for raw materials. (ii) Printed packaging materials should be stored securely in lock and key system to avoid unauthorized access. (iii) Each delivery or batch of printed or primary packaging materials should be given a specific reference number or identification mark. (iv) Outdated and obsolete primary or printed packaging materials should be destroyed by suitable and approved method of destruction and records maintained. The destruction of printed packaging materials should be done under the direct supervision of a responsible or QA person. Packaging Materials (v) 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 instruction.  Quantitative records of printed packaging materials should be maintained to the last unit of counting. All audit and inspecting authorities are very much rigid and strict on this issue; since unaccounted printed packaging materials have a potential danger of its misuse. (vi) A detailed SOP should be available for dispensing of packaging materials. Only authorized persons should do dispensing and make records of all the activities. (vii) A separate sampling room should be provided for sampling of primary packaging materials, which should be a fairly clean area. Intermediate and Bulk Products Intermediate or bulk product may be defined as the material, which has started processing but not yet got converted into the finished saleable product e.g.  Granulated materials ready for compression.  Compressed tablets for coating or packaging.  Filtered or unfiltered liquids for oral or injectable etc. These products should be kept under appropriate storage conditions of temperature, relative humidity, class of air etc. In pharmaceutical industry normally main or central warehouse is responsible for management of raw, packaging and finished products. However intermediate and bulk product storage is the responsibility of the production department. Intermediate or bulk products purchased as such should be handled on receipt as though they were raw materials. Finished Products Finished products are products which are in the marketable pack. These products should be held in quarantine until their final release. Each batch of the finished product should be tested as per laid down testing procedure against its specifications and then only released for distribution or sale. After being released, finished products should be stored as usable stock under conditions established by the manufacturer. Products failing to meet the established specifications or any other relevant quality criteria should be rejected. Reprocessing may be performed, if feasible, but the reprocessed product should meet all specifications and other quality criteria prior to its acceptance and release. Finished Products SOP on releasing of the finished product: SOP on releasing of finished product should address the following points: (i) Who is the authority to release a batch? He may be:  Quality Assurance head, or  Any other person suitably authorized for this purpose. (ii) Before releasing the finished product; at least following points should be considered. (a) Completed Batch Production and Control Record (BPCR). (b) Test reports of IPQC. (c) Test reports of finished product/ analysis. (d) Deviations reports if any. (e) Sterility reports along with environmental conditions reports, in case of sterile products. (f) Any other reports related to the manufacturing and packaging of the batch. Finished Products SOP on releasing of the finished product: (iii) Partial batch release is generally not acceptable practice. It can be done only under justified exceptional conditions, under deviation control system. (iv) A formal report/ certificate of release may be prepared and should become a part of the BPCR. Rejected Products Rejected materials may be defined as materials at any stage, which have been tested against a set of predefined specifications and found not meeting the specifications fully. We can deal with such materials mainly in two ways: (a) Reprocess and retest the materials to see whether it meets our specific requirements. (b) Destroy or send it to the supplier (if it is a purchased material). Whatever action taken should be approved by authorized personnel and properly documented. Rejected Products Rejected materials and products should clearly marked as such and stored separately in restricted areas. Such areas in industry are normally painted RED in color to make it distinguishable easily. Rejected Products SOP on handling of rejected materials: This SOP should cover the following points: (i) How rejected materials are identified? (ii) How these materials are stored? (iii) What records should be maintained? (iv) How these materials are disposed off? (v) What precautions are taken to deal with rejected printed materials? (vi) What precautions are taken to avoid accidental use of rejected materials? (vii) Who has the authority to order disposal of rejected materials? etc. Note: A trend analysis report of rejected materials may be prepared and studied to identify the reasons for rejection and take suitable corrective action to avoid such recurrences in future. Reprocessed Products Rejected production batches should be reprocessed in exceptional situations. Such reprocessing should be permitted only if the reprocessed batch is going to meet the same specification after reprocessing and not likely to have any untoward effect on the product and ultimate user till the expiry period of the product. A detailed record of such reprocessing should be kept. Reprocessed batches should be given a new number by means of which, such batches can be identified as reprocessed batches. Such batches should be separately monitored throughout their shelf life. Recovered Products Recovery: The addition of all or part of earlier batches, conforming to the required quality, into a batch of the same product at pre-defined stage of manufacture. Normally between 5 to 10% of recovery can be added into a fresh batch, provided that the recovered material is meeting the specifications. 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. Such additions must be properly authorized and recorded. Recalled Products Products, which are already distributed or sold, may be required at times to be recalled from market for various reasons e.g.  substandard quality detected after the product was distributed,  emerging risk or potential toxicity.  damage of goods during transit. Visit: https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts Such recalled products should be clearly identified and stored separately in a secure area until a decision is taken on their fate. Such decision should be made as soon as possible. Recalled Products Depending on the situation, different actions can be made on such products when returned from the market: (i) Physically examine the condition of the goods returned. Also check all the relevant documents. (ii) Ask QC department to evaluate the quality of the goods received, and take a decision on whether these products can be reprocessed and recovered or needs to be destroyed. (iii) If it is possible to reprocess and recover, then such products after reprocessing and retesting may be considered for re-labelling and repacking. Reagents and Culture Media Following points should be considered regarding management of reagents and culture media: (i) All reagents and culture media should be recorded upon receipt or preparation. (ii) Reagents made up in the laboratories should be prepared according to written procedures and appropriately labelled. Such labels should indicate following information viz. (a) Name of the reagent. (b) Nominal concentration. (c) Standardization factor. (d) Shelf life (or use before date). (e) Date when re-standardization is required. (f) The storage conditions. (g) Name/Signature and date of the person who has prepared and standardized the reagent. Waste Materials Pharmaceutical manufacturing operations generate lot of waste materials. These materials can be classified mainly in two categories: (i) Trash: Which do not have any resale value and may be disposed off by proper method depending upon the nature of the trash. (ii) Scrap: Which do have a resale value and may be sold to scrap dealers, after proper segregation. Before disposal of these materials, they can be segregated in different categories: (1) Paper (2) Aluminum foils (3) Plastic (4) Glass (5) Metallic containers etc. Provisions should be made for proper and safe storage of waste materials awaiting disposal. Waste Materials Waste materials should not be allowed to accumulate. It should be collected in suitable containers for removal to collection points outside the buildings, and disposed off safely and in a sanitary manner at regular intervals. Toxic substances and flammable materials should be stored in suitably enclosed cupboard, as required by national legislation. Flammable solvent drums must be washed thoroughly before disposal since they pose a potential danger of fire or explosion.  Reference Standards Reference standards may be available in the form of official (primary) reference standards. Official reference standards should be used only for the purpose described in the appropriate monograph. Secondary or working reference standards prepared by the producer should be tested, released and then stored in the same way as official standards. All in house reference standards should be based on official reference standards, when available. They should be kept under the responsibility of a designated person in a secure area. Miscellaneous Materials All those materials, which do not specifically fall under the category of RM/PM Intermediates, bulk and finished pharmaceuticals may be considered under this category of miscellaneous materials. Such materials like, rodenticides, insecticides, fumigating agents and sanitizing materials fall under this category. These materials should not contaminate equipment, raw materials, packaging materials, in-process materials or finished products.