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 7.5 on Production and Service Provision, also contains several new provisions:

  • Requirements for equipment and utensil cleaning and sanitization are expanded under clause 7.5.1 (Control of Production and Service Provision). In addition to the expectations noted in the IPEC–PQG guide, the standard requires the establishment of criteria to confirm cleaning effectiveness, requires chronological records of cleaning activities and identification of the cleaning status of equipment.
  • There is a requirement to demonstrate ongoing evidence of process capability under Clause 7.5.2 (Validation of Processes for Production and Service Provision).
  • Clause 7.5.3 (Identification and Traceability) stipulates documentation that defines identification and traceability for raw materials in continuous processing. The IPEC-PQG guide suggests using the time material was processed for traceability. This clause also requires that labeling include the manufacturing address or a reference to the site of manufacture.
  • Under Section 7.5.5 on Preservation of Product, the manufacturer is expected to justify the handling and storage conditions for quality critical materials.
  • Where excipient is shipped in bulk, there is to be a list of restricted or allowed previous cargoes for non-dedicated bulk transport equipment according to Clause (Excipient Delivery).

Section 7.6, Control of Monitoring and Measuring Equipment, describes the expectations for measuring and test devices used to make quality-critical measurements.

There are several new expectations under Section 8.2.4, Monitoring and Measurement of Product:

  • Clause (Laboratory Controls) adds the requirement to provide documentation of sample preparation to show conformance with the test method. In addition there is a requirement to reference the test method. This documentation will facilitate the investigation of Out-of-Specification test results.
  • Clause (Laboratory Procedures) notes that reagents and test solutions are to have expiration or re-standardization dates.
  • Clause (Certificate of Analysis) includes the provision noted in the IPEC–Americas COA guide to include the "manufacturer's name and site of manufacture or reference to the site of manufacture" (5).

Section 8.3 on Control of Nonconforming Product, adds a couple of requirements:
  • Nonconformance is to be investigated to identify the root cause and potential impact to other batches or products.
  • Under Clause 8.3.2 (Reworking) customers are to be notified if they are provided with a reworked batch. Such material represents a potential significant change since routine processing was not followed.

The last addition of note is in Section 8.4 on Analysis of Data, which requires monitoring of nonconformance with this standard and of supplier nonconformance are new requirements.


This article highlights the new requirements for excipient GMP as reflected in NSF 363. It expresses the opinion of the author as to what requirements in the draft ANSI excipient GMP standard differ from the IPEC–PQG Excipient GMP Guide. It is important to note that at the time this article was prepared, the public comment period for the standard had just been completed. Based upon input, requirements as described here may be modified. The reader is thus urged to review the requirements in the approved NSF 363 standard for applicability to their manufacturing operation. While certain new requirements are expressed in the standard, they either evolved from implied expectations in the excipient GMP guide or are enhancements resulting from the current business and regulatory climate. NSF 363 is organized in accordance with ISO 9001 but adds new clauses where appropriate. The organization of this American National Standard will facilitate submission of the standard to ISO for their adoption as a global standard.

Irwin Silverstein, PhD, is vice-president and chief operating officer at International Pharmaceutical Excipients Auditing, 1655 N. Fort Myer Drive, Suite 700, Arlington, VA 22209, tel. 703.351.5266.


1. NSF Joint Committee, Draft Good Manufacturing Practices (GMP) for Pharmaceutical Excipients (2012).

2. IPEC–PQG, Joint IPEC–PQG Good Manufacturing Practices Guide for Pharmaceutical Excipients (2006).

3. ANSI, Essential Requirements: Due Process Requirements for American National Standards.

4. IPEC–Americas, Significant Change Guide for Bulk Pharmaceutical Excipients (2009).

5. IPEC–Americas, Certificate of Analysis Guide for Bulk Pharmaceutical Excipients (2000).


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