Supplements to the PQRI Workshop Results - Pharmaceutical Technology

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Supplements to the PQRI Workshop Results

Pharmaceutical Technology

21 CFR 211. 194 (a) (2) - A statement of each method used in the testing of the sample. The statement shall indicate the location of data that establish that the methods used in the testing of the sample meet proper standards of accuracy and reliability of the sample meet proper standards of accuracy and reliability as applied to the product as applied to the product tested. (If the method employed is in the current revision of the United States Pharmacopeia, National Formulary, AOAC INTERNATIONAL, Book of Methods, or in other recognized standard references, or is detailed in an approved new drug application and the referenced method is not modified, a statement indicating the method and reference will suffice). The suitability of all testing methods used shall be verified under actual conditions of use.

21 CFR 314.70 Supplements and other changes to an approved application:

(d) Changes to be described in an annual report (minor changes): (1) Changes in the drug substance, drug product, production process, quality controls, equipment, or facilities that have a minimal potential to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product as these factors may relate to the safety or effectiveness of the drug product must be documented by the applicant in the next annual report in accordance with 314.81(b)(2).

(2) These changes include, but are not limited to:

(i) Any change made to comply with a change to an official compendium, except a change described in paragraph (c)(2)(iii) of this section, that is consistent with FDA statutory and regulatory requirements.

21 CFR 314.70 (c) Changes requiring supplement submission at least 30 days prior to distribution of the drug product made using the change (moderate changes).

(2) These changes include, but are not limited to:

(iii) Relaxation of an acceptance criterion or deletion of a test to comply with an official compendium that is consistent with FDA statutory and regulatory requirements.

See also, FDA's Guidance to Industry, Changes to an Approved NDA or ANDA; Specifications: Use of Enforcement Discretion for Compendial Changes, dated Nov. 19, 2004 at http://

Appendix: definitions and regulations, Compliance Policy Guides

Sub Chapter 420 - Compendial /Test Requirements

Sec. 420.100: Adulteration of Drugs Under Section 501(b) and 501(c) of the Act. *Direct Reference Seizure Authority for Adulterated Drugs Under Section 501(b)* (CPG 7132a.03)

Any official drug which, when tested by compendial methods, fails to conform to compendial standards for quality, strength, or purity, is adulterated unless the differences from such standards are plainly stated on the drug's label.

Sec. 420.200 - Compendium Revisions and Deletions (CPG 7132.02)

All official articles shipped prior to the date that the current USP- NF became official should be in compliance with the official compendia in effect at the time of shipment.

Sec. 420.300 - Changes in Compendial Specifications and NDA Supplements (CPG 7132c.04)

Any change in the compendial specifications for an NDA drug will normally require the submission of an NDA supplement.

Sec. 420.400 - Performance of Tests for Compendial Requirements on Compendial Products (CPG 7132.05) [Section 420.400 presently is under revision by FDA]

Compendial methods need only be applied, as a batch release test, where a firm has made specific commitments to do so (as in a new drug application), or where the official method is the only appropriate test. Neither the USP- NF nor the CGMP regulations necessarily require a firm to utilize, as a batch release test, the methods and procedures stated in the official compendia. What is required is that official drug products conform to the appropriate compendial standards.

The manufacturer's specifications for standards of strength, quality and purity may be less stringent in those cases in which the differences from the official standards are stated on the product label.


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