Excipients, novel

Appendices This section is most likely to contain additional data associated with biological-based products. It should contain information as regards the facilities and equipment used for the manufacture of biotech products. Assessment of the risk of contamination from adventitious agents such as transmissible spongiform encephalopathy agents (TSEs), bacteria, mycoplasma, fungi or viruses should also be provided. Additional information on novel excipients that have not been used before should also be included in this section. 

Where an unusual excipient is chosen, or where an established excipient is chosen for a dosage form that results in its administration by a novel route of administration, then additional data will need to form part of the application. In effect, a novel excipient will need to be supported by data similar to those required for a new drug, with full supporting data including composition, function, and safety. Novel excipients include the components of the matrix in prolonged release products, new propellants, and new permeability enhancers. The exception to this need for extensive supporting data would be for a material already approved for food use and administered by the oral route or a material already approved for cosmetic use with a topical route of administration. In all cases the quality of the excipients has to be described adequately and shown to be satisfactory (which will depend on its role). 

For any new excipients, APIs or drug products (where new does not necessarily mean novel, but new to the receiving site) there are additional testing criteria, e.g. supplier audits, third-party contract laboratory audits, analytical method transfers, sample management/tracking, etc. For those key excipients, where there is on-site historical experience, it still behoves both parties to check whether the local grade/supplier used by the CMO is equivalent to that used by the supplier (Worsham, 2010). There are many examples of differences in excipient physical properties, e.g. particle size, which have been attributed to different excipient sources that could ultimately impact on the performance of those excipients in formulated products (Frattini and Simioni, 1984 Dansereau and Peck, 1987 Phadke et al., 1994 Lin and Peck, 1994). 

Appropriate barrier methods and vaginal formulations are the first line of defense against the prevention of pregnancy and STDs. Recognition of this fact and initiation of work to develop traly novel systems should be a major development focus. Indeed, major efforts are under way to develop new and more effective microbiocides, excipient delivery vehicles, and subsequent formulations. 

BMS-204352, a novel substituted 3-fluorooxindole, is a potassium channel opener being developed for the treatment of stroke. Nassar et al. [96] reported on the development of a non-aqueous parenteral formulation of BMS-204352. This formulation was composed of a mixture of PEG 300, polysorbate 80, ethanol and water. The authors reported on the formation of 1-hydroxymethyl adduct of BMS-204352 (formaldehyde adduct), which was linked with residual levels of formaldehyde in the polymeric excipients. 

The toxicological characteristics of any novel adjuvants, carriers, or excipients should be addressed. 

A particularly interesting, and extremely simple, method of activating enzymes for use in nonaqueous media is lyophilization in the presence of nonbuffer salts. In the process, a great deal about excipient-enzyme-water interactions has been learned along with an appreciation of how enzymes adjust to novel microenvironments while retaining their intrinsic catalytic properties. 

Excipients manufacture The manufacture of novel excipients may be provided in an application or supporting DMF. Typically these excipients are noncompendial and are used in specialized dosage forms and drug delivery systems. CDER chemists are responsible for the scientific reviews and evaluation of the records and data associated with the manufacture of these novel excipients. The review will include starting materials, key intermediates, reagents, and solvents. cGMP inspections by the Field usually will be performed on request from CDER. 

Memiolu, E., Bochot, A., Sen, M., Sharon, D., Duchene, D., Hincal, A.A. (2002). Amphiphilic p-cyclodextrins modified on the primary face synthesis, characterization and evaluation of their potential as novel excipients in the preparation of nanocapsules. Journal of Pharmaceutical Sciences, 91, 1214-1224. 

FDA guidancesa serve as a flexible approach to assist compliance with FDA s requirements. Safety testing of novel and potential excipients is addressed in the... 

The existing structure for review of excipient ingredients has several structural defects that result in significant disincentives in the development of novel excipients. Currently, only excipients that have been approved in an NDA are subject to a USP/NF monograph, or excipients that have an FDA- or a JECFA-sanctioned food... 

In an attempt to increase the likelihood of regulatory and pharmaceutical industry acceptance of new excipients, excipient manufacturers have made several attempts to foster a regulatory environment that provides mechanisms for acceptance of new and novel excipients. Attempts to create a preapproval review or formal status for excipients have not been successful, and are likely not to be in the interests of the industry nor economically feasible for regulatory agencies. 

All of these efforts were directed at standardizing excipient manufacture and use, and have been important in creating a regularized regulatory environment for excipients. Nevertheless, these steps are primarily directed toward the safety and use evaluation of existing excipients, and do little to provide any indicia of acceptability for novel ingredients. 

Recently, IPEC has taken the initiative in evaluating different models for evaluation of novel excipient ingredients in an attempt to obtain some acceptance of new... 

Commodity prices, therefore, will be realized only several decades after the introduction of a novel excipient and only when the bulk is generic and/or when there are other excipients that are interchangeable for the function the excipient... 

The U.S. Food and Drug Administration (FDA) defines novel (new) pharmaceutical excipients as those substances used in the United States for the first time in a human drug product or by a new route of administration (1). The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) includes sections in its Common Technical Document (CTD) that details the information required for the approval of novel (new) excipients. Information on the control of excipients is included in Section P.4 of the CTD, and any additional information that may be required should be included in Appendix A.3 of the CTD. 

Stefely JS, Duan DC, Myrdal PB, Ross DL, Schultz DW, Leach C. Design and utility of a novel class of biocompatible excipients for HFA-based MDIs. Paper presented at RDD VII, 2000. 

Stefely JS. Novel excipients for inhalation drug delivery expanding the capability of the MDI. Drug Delivery Technol 2002 2(6) 62, 64-69. 

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