The American National Standard for Excipient GMP - Pharmaceutical Technology

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The American National Standard for Excipient GMP
The author reviews significant changes to GMP for excipients in the forthcoming American National Standard, including a risk-based approach to excipient manufacture, why new requirements were proposed, and their potential impact to excipient manufacturers.


Pharmaceutical Technology
Volume 36, Issue 3, pp. s38-s41

Section 7 on Excipient Realization, further provides for risk assessments, as follows:

  • Clause 7.4.1 (Purchasing/Purchasing Process) requires the identification of quality-critical materials and services through risk assessment. The requirements of this clause are applicable only to those materials and services identified as quality-critical, except for the general expectation to have an agreed specification from approved suppliers. While neither the standard nor the IPEC–PQG Excipient GMP guide provide criteria for the determination as to whether a material or service is quality-critical, the assessment should be based on the potential impact to excipient quality (2). The suppliers of quality critical raw materials should be expected to notify the manufacturer of a process change so that the excipient manufacturer can evaluate the change for the potential impact to the excipient.
  • Clause 7.5.5.1 (Production and Service Provision/Preservation of Product/Raw Material Packaging Systems) requires a risk assessment to assure the storage and handling of raw materials provides suitable protection against deterioration or contamination and that identification labels remain legible.
  • Clause 7.5.5.2 (Production and Service Provision/Preservation of Product/Excipient Packaging Systems) provides for a risk assessment only where reusable containers are returned for further use.

The only requirement for risk assessment in Section 8, Measurement, Analysis and Improvement, is in clause 8.3.2 (Control of Nonconforming Product/Reworking). Here, a risk assessment is required to assess the risk of the rework operation to excipient quality.

In conclusion, the provisions for risk assessment in NSF 363 are new in that they are to be formally conducted and documented. Informal assessment of risk to excipient quality has always been an expectation in IPEC excipient GMP guides however.

Other noteworthy requirements. Several other provisions in NSF 363 are either new to excipient GMP requirements or differ from that suggested in the IPEC–PQG Excipient GMP guide (2). In particular, the excipient manufacturer should be aware of the following differences.

Clause 4.2.4 (Quality Management System/Documentation Requirements/Control of Records) requires that records be kept for 1 year beyond the excipient expiration date or first re-evaluation date. The standard further states that where the manufacturer does not stipulate a re-evaluation or expiration date, the records should be retained for five years. The IPEC-PQG Excipient GMP guide merely suggests keeping records for a defined period.

Specified responsibilities of an independent Quality Unit are noted in Clause 5.5.1 (Management Responsibility/Responsibility, Authority, and Communication/Responsibility and Authority) with allowance to delegate some duties. While these responsibilities are also listed in the IPEC–PQG Excipient GMP guide as is allowance for delegation, the standard further notes that ultimate responsibility for oversight and approval remains with the Quality Unit.

As noted, Clause 7.4.1 (Purchasing Process) requires the identification of quality-critical materials and services. However, unlike the IPEC–PQG Excipient GMP guide, the standard specifically includes packaging materials. Also where the guide notes that periodic audits may be required, the standard notes the assessments are to be ongoing. The expectation of the standard is for the manufacturer to continuously monitor the conformance of these suppliers to the purchasing agreement.

Clause 7.4.3 (Purchasing/Verification of Purchased Product) adds several new requirements:

  • Justification for not sampling any incoming material
  • Verification of the measurements reported on the supplier Certificate of Analysis (COA)
  • Verification that the Certificate of Conformance for packaging components references the current agreed specification.


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