Technical Note: The Case for Supplier Qualification - Pharmaceutical Technology

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Technical Note: The Case for Supplier Qualification
This article demonstrates that test results support the position of FDA on the importance of an appropriate supplier-qualification program.

Pharmaceutical Technology
Volume 33, Issue 10, pp. 84-88

Excipient sampling program

IPEA developed scientific data to demonstrate the quality of these excipients in the marketplace. The IPEA sampling protocol for excipients from commercial packages was intended to obtain unbiased test results for these excipients in the USP-verified laboratories for comparison against USPNF requirements. Several excipients from the established manufacturers and the two Asian manufacturers were shipped to the sample preparation site. The excipient packages provided were single samples; there were no excipients from multiple lots of the same product.

Table I: Copovidone NF from Asian manufacturer A.
IPEA supervised the preparation of test samples from the commercial packages. Before opening, each package was carefully examined to confirm the tamper-evident seal was in-place and the appearance of each package was documented, both through written observation and photography. Each package appeared to have been labeled and sealed by the manufacturer.

Table II: Povidone USP K-17 from Asian manufacturer A.
Each package was opened in an environmentally controlled room (temperature ~70 F, relative humidity ~35%) and the excipient was scooped into plastic 1-L bottles. The excipient was surface sampled with a scoop and the first bottle from each package was kept as retains. The sample bottles were labeled to indicate the excipient compendial name and coded so that their manufacturer was not disclosed. They were then sealed and sent to the established manufacturers' USP-verified laboratories for compendial testing.

Table III: Povidone USP K-17 from Asian manufacturer B.
On occasion, multiple samples of the same excipient from the same manufacturer were sent to the laboratories to reduce the likelihood of the analyst identifying the manufacturer of the sample and thus potentially adding bias to the results. Assessment of the reproducibility of laboratory test results was an added benefit arising from multiple samples. Matching excipient samples were tested at both established manufacturers' laboratories assessed under the USP-verified program.

Results and discussion

Table IV: Povidone USP K-12 from Asian manufacturer B.
The test results confirmed that all excipient produced at the established manufacturers met compendial requirements. Excipients from the Asian-based manufacturers failed to meet monograph requirements. Specifically, Copovidone NF from Asian manufacturer A failed to conform to the limit of monomers, content of polymerized vinyl acetate, and nitrogen. This is an indication that the polymer is deficient in vinyl acetate (see Table I). Povidone USP K-17 from Asian manufacturer A exceeded the limit for hydrazine and K-value (see Table II). Povidone USP K-17 from Asian manufacturer B exceeded the specified K-value and was high in ash (residue on ignition) and aldehydes (see Table III). Povidone USP K-12 from Asian manufacturer B exceeded the allowable limit for aldehydes (see Table IV). Povidone USP K-90 from Asian manufacturer B exceeded the allowable limit for vinyl pyrrolidinone (see Table V).


Table V: Povidone USP K-90 from Asian manufacturer B.
Several common excipients from the two Asian manufacturers, Nanhang Industrial and Tianjin Boai NKY International, and the established producers were evaluated for conformance to the current USPNF. For the Asian-based manufacturers, the data demonstrated that four of six Povidone lots sampled and one of two Copovidone lots failed to conform to the monograph. It was noted that two of three lots of Crospovidone tested high for heavy metals in one laboratory but was found to conform by the other.

The results of this study illustrate the importance of adequately qualifying the supplier of components. It is important to confirm the quality of the excipient using a scientific sampling plan and to perform complete testing until there is adequate assurance in the reliability of the manufacturers test data. In addition, it is essential to audit the site of manufacture because no amount of laboratory testing can confirm that the quality system used to produce the excipient meets CGMPs. A site audit also can provide confidence that the manufacturer has the technical ability to produce the excipient in the commercial package.

Irwin Silverstein is vice-president and chief operating officer of International Pharmaceutical Excipients Auditing, a subsidiary of the International Pharmaceutical Excipients Council, tel. 732.463.8710,


1. S. Wolfgang, "Regulatory Perspective on Assuring Excipient Quality," presented at the USP International Excipient Workshop, Washington, DC, July 2009.

2. A.R. Sibille, "Control of Components and Drug Product Containers and Closures, Subpart E" in Good Manufacturing Practices for Pharmaceuticals, J. Nally, Ed. (Informa Healthcare, 6th ed., 2007), pp. 76–77.


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