Receipt, Sampling, Testing, and Approval of Raw Materials

While the COA is the excipient manufacturer s responsibility, once the material is received, it is the drug product manufacturers responsibility to verify the product and ensure that it is properly tested, handled, and stored. Upon receipt of a shipment, each lot of excipient will be withheld from use until the lot is sampled, tested, or examined according to the written procedures. The quality control (QC) personnel will examine each container for (i) manufacturer s name, (ii) manufacturer s lot number, (iii) leaks or spills, (iv) contamination, (v) breached containers, (vi) proper labeling, and (vii) material safety data sheet and determined material hazards. 

Representative samples of each shipment must be collected for testing as required by 211.84. (b). The number of containers to be sampled depends on the (i) component variability, (ii) confidence level, (iii) degree of precision desired, (iv) past quality history of the supplier, and (v) quantity needed for analysis and reserve samples. For hazardous or highly toxic raw materials, where on-site testing may be impractical, suppliers COA should be obtained, showing that the raw materials conform to specifications. In addition, the identity of these raw materials should be confirmed by examination of containers and labels. The lack of on-site testing for hazardous raw materials should be documented. 

Each bag or container of raw materials should be identified with a unique code, lot, or receipt number. This code should be used in recording the disposition of each lot. Raw materials will be held under quarantine until they are sampled, tested, and released. Raw materials should be carefully handled and stored to avoid any contamination or cross contamination. When bagged and boxed raw materials need to be stored, it must be done so in adequately cleaned buildings that are free of infestation by rodents, birds, insects, and other vermin, and the building should be maintained. A controlled environment may be necessary to avoid microbial contamination or degradation caused due to exposure to heat, air, or light. When the raw materials are stored outdoors, the containers should be adequate for the outdoor storage. 

Representative samples of each lot will be collected for testing in accordance with the established procedure. The number of containers to sample and the sample size should be based upon appropriate criteria as required by 211.84 (3) (e.g., raw material variability, confidence levels, degree of precision desired, past quality history of the supplier, and the quantity needed for analysis). Sample containers should be properly labeled. The label should include, at minimum, information about the sample name, manufacturer name, sample size, and date and hour of sampling. Raw material containers selected for sampling should be opened, sampled, and resealed in a manner that prevents contamination of their contents and of other raw materials. 

Materials are held in quarantine until the QC approves the product. Once the product is approved, the QC inspector will stamp the material as released and the product is transferred from quarantine to the available inventory area for use. If the QC lab rejects the raw material, it will be properly identified and moved into a separate indentified area. The system should be designed to avoid using the rejected materials in the operation. All the acceptable raw materials should be stored under appropriate conditions the drums will be rotated so that the oldest stock is used first. Raw materials should be reevaluated, as necessary, to determine their suitability for use (e.g., after prolonged storage or after exposure to heat or high humidity). 

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Written procedures should be established describing the purchase, receipt, identification, quarantine, storage, handling, sampling, testing, and approval or rejection of raw materials. Such procedures should be followed. 

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