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name (nonproprietary name) of a drug or component is the offi cial title used for the drug or component in an offi cial compendium such as USP or NF (USP–NF), unless FDA has designated another name via regulation. Thus, workshop attendees seemed to agree that when a USP–NF standard exists, the excipient would ideally appear in IID under the offi cial title established in the USP–NF. However, this is not always the case.
A major eff ort is underway at FDA to rectify current entries in the data- base and to provide the means going forward to improve the quality and utility of data. However, many excipients with new or revised monographs in the current USP work plan still use nomenclature that traces to non-pharmaceutical use. For example, excipients used in topical drugs are generally marketed using cosmetic naming convention. The FDA Substance Registration System (SRS) provides the preferred name as well as synonyms for excipients which can help answer questions such as whether an excipient is considered new. Thus, USP compendial nomenclature could be a source of preferred names, and applicants can assist by using preferred names in the composition statement section of the application. For excipients that are non-compendial, SRS can be accessed to fi nd the preferred name for the composition statement.
Co-Processed Excipients
A co-processed excipient contains more than one excipient whereby co-processing does not involve formation of a chemical bond between any of the individual excipients. The USP Excipients Expert Committee (Excipients EC) deemed it appropriate to include co- processed excipients in the NF because these excipients possess certain physical characteristics that are diff erent from or altered from their corresponding simple physical admixtures. Co-processed excipients should follow proposed criteria established to defi ne when USP would consider advancing a prospective new monograph for a co-processed excipient into NF. These criteria were developed to diff erentiate multi-component co-processed excipients from the more commonly encountered excipients that have been the norm in NF. Due to the complex processes used to manufacture multi-component excipients, their proprietary nature, and the lack of comprehensive understanding of these types of excipients, the EC proposes to limit the current criteria to solid co-processed materials. A request for revision (RFR) to develop a co-processed excipient monograph should consider the criteria appearing in the Stimuli article on Co-processed Excipients.12
When the excipient is submitted as a potential NF monograph, information relating to its quality must meet current NF submission requirements.13
Atypical Active Ingredients
USP also contains several monographs for excipients used in drugs as active ingredients, that are termed atypical actives or dual-use drug ingredients. Monographs for excipients used as atypical actives are typically published in the USP section of the USP–NF with the title
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Table 1. Request for Revision for an NF excipient monograph- the RFR typically includes the following sections (not every excipient monograph will contain every section)
Name (title) Description (structure, molecular weight, CAS) Defi nition Identifi cation Assay Other components Impurities Specifi c tests
Additional requirements • Packaging and storage • Labeling • Reference Standards
listed in the NF section, for example, “Glycerin – see Glycerin General Monograph), indicating that it is used as both an excipient and active ingredient. Labeling to indicate compliance with either USP or NF (or both) could signal the intentions of manufacturers regarding how an ingredient was designed to be used. This is an important distinction because an excipient’s use as an API generally leads to the most stringent ingredient Good Manufacturing Practice (GMP) expectations.
Excipient monographs for atypical active ingredients are also part of the USP Up-to-Date initiative, with a primary focus on replacing non- specifi c identifi cation tests with those suitable for compliance with regulatory requirements for excipient identity. An equally important goal for monograph development is replacement of non-specifi c assay methods and addition of analytical methods that allow better measure- ment of the purity of excipients used as active ingredients. Polyethylene Glycol (PEG) 3350 USP is an excellent example. PEG 3350 was originally included in the PEG NF monograph as one of several grades of the excipient. PEG NF does not contain an identifi cation test and the assay measures average molecular weight. The Excipient EC worked with stakeholders to develop a separate PEG 3350 USP monograph by proposing appropriate test procedures and methodologies in Pharmacopeial Forum (PF) 39(6) and PF41(4) to uniquely identify PEG 3350 and to properly determine the product’s strength (content).
Impact of Excipient Variability on Drug Product
Excipients are known to exhibit variability in their critical material attributes (CMAs) due to various factors associated with excipient manufacturing.14
Because generally excipients are added in fi xed
amounts when products are manufactured, such variability could translate into product and process variation. The identifi cation and evaluation of excipient CMAs hold promise for the development of novel control strategies that could lead to improved quality and manufacturing capability throughout a product’s life-cycle. The USP Excipient Workshop included a presentation about the National Institute of Pharmaceutical Training and Education (NIPTE)/FDA PharmaHub database,15
a unifi ed attempt to catalog data from testing
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