Composition of the USP Pharmacists Pharmacopeia (Cont'd)

We will continue to look in detail at more selected portions of the Introductory Material, as follows.

INTRODUCTORY MATERIAL

3. CONFORMANCE TO STANDARDS

3.10. Applicability of Standards

Standards for an article recognized in the compendia (USP-NF) are expressed

• in the article's monograph,
• in applicable general chapters, and
• General Notices.

Unless specifically exempted elsewhere in a compendium, the identity, strength, quality, and purity of an article are determined

• by the official tests, procedures, and acceptance criteria,
• other requirements incorporated in the monograph,
• in the General Notices, or
• in the applicable general chapters.

In a monograph, requirements for official articles are indicated in two ways: (1) for certain monographs, after the official title, the primarily informational portions of the text appear first, followed by the text comprising requirements, the latter section of the monograph being introduced by a double arrow symbol "; and (2) for monographs more recently redesigned, requirements appear in the official title and in any text beginning with the section titled "Definition". In either format, information that appears: (1) after the title but before the double arrow symbol; (2) after the title but before the section titled "Definition"; or (3) in or after the section titled "Auxiliary Information" is provided for informational purposes. See Preface for information related to updates to Chemical Information.

Where conformance to any specifications represented by Chemical Information is critical to establishing identity, purity, potency, or another quality attribute of an official article, the monograph will include such specifications in the text that states requirements.

"Applicable general chapters" means general chapters numbered below 1000 or above 2000 that are made applicable to an article through reference in General Notices, a monograph, or another applicable general chapter numbered below 1000. Where the requirements of a monograph differ from the requirements specified in these General Notices or an applicable general chapter, the monograph requirements apply and supersede the requirements of the General Notices or applicable general chapters, whether or not the monograph explicitly states the difference.

General chapters numbered 1000 to 1999 are for informational purposes only.

The standards in the relevant monograph, general chapter(s), and General Notices apply at all times in the life of the article from production to expiration.

Official products are prepared according to recognized principles of good manufacturing practice and from ingredients that meet USP or NF standards, where standards for such ingredients exist.

Official substances are prepared according to recognized principles of good manufacturing practice and from ingredients complying with specifications designed to ensure that the resultant substances meet the requirements of the compendial monographs.

3.10.10. Applicability of Standards to Drug Products, Drug Substances, and Excipients

The applicable USP or NF standard applies to any article marketed in the United States that (1) is recognized in the compendium and (2) is intended or labeled for use as a drug or as an ingredient in a drug. Such articles (drug products, drug substances, and excipients) include both human drugs (whether dispensed by prescription, "over the counter", or otherwise), as well as animal drugs. The applicable standard applies to such articles whether or not the added designation "USP" or "NF" is used. The standards apply equally to articles bearing the official titles or names derived by transposition of the definitive words of official titles or transposition in the order of the names of two or more drug substances in official titles, or where there is use of synonyms with the intent or effect of suggesting a significant degree of identity with the official title or name.

3.10.30. Applicability of Standards to the Practice of Compounding

USP compounding practice standards, Pharmaceutical Compounding-Nonsterile Preparations <795> and Pharmaceutical Compounding-Sterile Preparations <797>, as appropriate, apply to compounding practice or activity regardless of whether a monograph exists for the compounded preparation or these chapters are referenced in such a monograph. In the United States, <795> and <797> are not applicable to drugs compounded by entities registered with FDA as outsourcing facilities as defined by FDCA § 503B, because such facilities are required to comply with FDA's current good manufacturing practice requirements. Compounded preparations, including drug products compounded by outsourcing facilities, may also be subject to applicable monographs; see section 2.20 Official Articles and section 4.10 Monographs.

3.20. Indicating Conformance

A drug product, drug substance, or excipient may use the designation "USP" or "NF" in conjunction with its official title or elsewhere on the label only when (1) a monograph is provided in the specified compendium and (2) the article complies with the identity prescribed in the specified compendium.

When a drug product, drug substance, or excipient differs from the relevant USP or NF standard of strength, quality, or purity, as determined by the application of the tests, procedures, and acceptance criteria set forth in the relevant compendium, its difference shall be plainly stated on its label. For general requirements relating to specific monograph sections, see section 5. Monograph Components.

Because monographs may not provide standards for all relevant characteristics, some official substances may conform to the USP or NF standard but differ with regard to nonstandardized properties that are relevant to their use in specific preparations. To assure interchangeability in such instances, users may wish to ascertain functional equivalence or determine such characteristics before use.

4.10.10. Applicability of Test Procedures

A single monograph may include more than one tests, procedures, and/or acceptance criteria for the same attribute. Unless otherwise specified in the monograph, all tests are requirements. In some cases, monograph instructions allow the selection of tests that reflect attributes of different manufacturers' articles, such as different polymorphic forms, impurities, hydrates, and dissolution. Monograph instructions indicate the tests, procedures, and/or acceptance criteria to be used and the required labeling.

4.10.20. Acceptance Criteria

The acceptance criteria allow for analytical error, for unavoidable variations in manufacturing and compounding, and for deterioration to an extent considered acceptable under practical conditions. The existence of compendial acceptance criteria does not constitute a basis for a claim that an official substance that more nearly approaches 100% purity "exceeds" compendial quality. Similarly, the fact that an article has been prepared to tighter criteria than those specified in the monograph does not constitute a basis for a claim that the article "exceeds" the compendial requirements.

An official product shall be formulated with the intent to provide 100% of the quantity of each ingredient declared on the label.

The acceptance criteria specified in individual monographs and in the general chapters for compounded preparations are based on such attributes of quality as might be expected to characterize an article compounded from suitable bulk drug substances and ingredients, using the procedures provided or recognized principles of good compounding practice, as described in these compendia.

4.20. General Chapters

Each general chapter is assigned a number that appears in angle brackets adjacent to the chapter name (e.g., Chromatography 〈621〉). General chapters may contain the following:

• Descriptions of tests and procedures for application through individual monographs,
• Descriptions and specifications of conditions and practices for pharmaceutical compounding,
• General information for the interpretation of the compendial requirements,
• Descriptions of general pharmaceutical storage, dispensing, and packaging practices, or
• General guidance to manufacturers of official substances or official products.

When a general chapter is referenced in a monograph, acceptance criteria may be presented after a colon.

Some chapters may serve as introductory overviews of a test or of analytical techniques. They may reference other general chapters that contain techniques, details of the procedures, and, at times, acceptance criteria.

Compounding Monographs

Where a monograph for a compounded preparation calls for an ingredient in an amount expressed on the dried basis, the ingredient need not be dried before use if due allowance is made for the water or other volatile substances present in the quantity taken.

Specially denatured alcohol formulas are available for use in accordance with federal statutes and regulations of the Internal Revenue Service. A suitable formula of specially denatured alcohol may be substituted for Alcohol in the manufacture of official preparations intended for internal or topical use, provided that the denaturant is volatile and does not remain in the finished product. A preparation that is intended for topical application to the skin may contain specially denatured alcohol, provided that the denaturant is either a usual ingredient in the preparation or a permissible added substance; in either case the denaturant shall be identified on the label of the topical preparation. Where a process is given in the individual monograph, any preparation compounded using denatured alcohol shall be identical to that prepared by the monograph process.

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition

Did You Know (On School) ...

The following...

"All wish to possess knowledge, but few, comparatively speaking, are willing to pay the price." (Juvenal)

Teacher (to tardy student):   "Why are you late?"
Student:   "Well, a sign down there..."
Teacher:   "Well, what has a sign got to do with it?"
Student:   "The sign said 'school ahead, go slow.'"

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From Out of the Past

Don't try passing
On a slope
Unless you have
A periscope
     Burma-Shave