Receipt of Materials
Upon the receipt of any material, all documents associated with the shipment or delivery must be reviewed to ensure accuracy and completeness. Starting materials, both active pharmaceutical ingredients (APIs) and excipients should be purchased only from approved suppliers, according to the European Union (EU) good manufacturing practices (GMP) Section 5.26 and the World Health Organization (WHO) GMP Section 14.8.
INCOMING INSPECTION
The EU and WHO GMP have similar requirements. Each container should be inspected for at least integrity of package and seal and for correspondence between the order, the delivery note, and the supplier’s labels. If a company receives material made of different supplier lot numbers, each batch must be considered separately for sampling testing and release, according to EU GMP Sections 5.27 and 5.28 and WHO GMP Sections 14.9 and 14.10. Containers should be cleaned where necessary and labeled with the prescribed label. Any damage to containers or other problem that could adversely affect the quality of the material should be recorded and reported to the quality unit (QU) as per WHO GMP Section 14.11. Both GMP (EU GMP Section 5.30 and WHO GMP Sections 14.14 and 17.15) further prescribe that appropriate measures should be taken to assure the identity of the contents of each container of starting material either by identity testing of each container or validation of the supplier.
The United States 21 CFR 211.80a–d includes requirements for procedures to receive materials, to store them appropriately, and to identify them. The United States Food and Drug Administration (FDA) GMP Part 21.82a states that “Upon receipt and before acceptance, each container or grouping of containers of components, drug product containers, and closures shall be examined visually for appropriate labeling as to contents, container damage or broken seals, and contamination.”
Written procedures and records are required for the receipt of each delivery of starting material and primary and printed packaging materials. The record of the receipts should include the name of the material on the delivery note and the containers, the in-house name and/or code of material if different, date of receipt, the supplier’s name, and, if possible, the manufacturer’s name, the manufacturer’s batch or reference number, the total quantity and number of containers received, the batch number assigned after receipt, and any relevant comment (for example, state of the containers).
Written procedures for the internal labeling, quarantine, and storage of starting materials, packaging materials, and other materials, as appropriate, are needed, according to EU GMP Chapter 4, Section 4.19–4.21, WHO GMP 15.32–15.34, and 21 CFR 211.80(a–d), 82(a,b).
IDENTIFICATION AND LABELING OF STARTING MATERIALS
The information that should be recorded on the label for each delivery is prescribed in the EU GMP Section 5.29, WHO GMP Section 14.13, and 21 CFR 211.80d and includes the designated name of the product and internal code reference, the supplier’s batch number and control (lot number) provided on the receipt, the status of the contents, and an expiry date or date beyond which retesting is necessary. When fully validated computer systems are used, not all of the above information needs to be legible on the label. Material must be restricted until appropriate testing is performed and disposition obtained from the site’s QU.
API GMP FOR RECEIPT OF MATERIALS
In addition to the requirements for starting materials used for drug products, receipt of starting materials used in API manufacturing should comply with specific requirements. Before incoming materials are mixed with existing stocks (for example, solvents or stocks in silos), they should be identified as correct, tested (if appropriate), and released. Procedures should be available to prevent wrongly discharging incoming materials into the existing stock. If bulk deliveries are made in non-dedicated tankers, assurance of no cross-contamination from the tanker is advisable. Means of providing this assurance could include a certificate of cleaning, testing for trace impurities, and/or audit of the supplier. One or more of these processes should be used. Some starting materials may not be tested for compliance because of the hazards involved (for example, phosphorus pentachloride and dimethyl sulfate), and this nontesting is acceptable when a batch certificate of analysis (COA) is available from the vendor and when there is a reason based on safety or other valid considerations.