Supporting stability data

Drug Product Stability. A description of the stability protocols and results supporting the product s stability (expiration date and storage condition) should be provided. Stability data supporting the proposed shelf-life of reconstituted drug products and for all labeled dilutions also should be included. The stability protocol provided should include the following ... 

A homoleptic square-planar palladium(II) carbonyl complex [Pd(CO)4](Sb2Fii)2 that displays v(CO) at 2259 cm (the value for free CO is 2143 cm ) has been recently prepared. This is an exceptional complex, dubbed by the authors as superelectrophilic metal carbonyl . The very high value of v(CO) shows that the carbonyl hgands behave as a-donors (see Carbonyl Complexes of the Transition Metals). Additional data (e g. v(M )) and stability data support that this ligand is very weakly coordinated as only a a-donor. ... 

Often after extensive stability data have been collected, there is a desire to change the expiration dating of a product. In particular, the available stability data support either an extension or a reduction in the expiration date approved in the original filing. Changes in expiration dating is covered in the FDA guidance. 

Real-time stability data supporting expiration dating. 

Patients taking a pharmaceutical product for a particular malady expect the product to be safe and efficacious. Regulatory agencies worldwide demand that the product retains its identity, quality, purity, and potency for the time that it is commercially available. Consequently, the agencies expect to see stability data supporting the proposed shelf life in the marketing appHcation. 

Listed below in tabular form are the available parameters found for over 43 selected PBX formulations, supported by unclassified refs. Table 3 presents the nomenclature and formulation of each compn Table 4, sensitivity and stability data and Table 5, performance parameters... 

Any residual doubt about the actual 7r-stabilization of such carbanions, that is, the question concerning the importance of resonance structure 52a, has been decisively banished by an XRD analysis of the lithium bis(12-crown-4) salt of dimesityl(methyl)borane (54).56 Noteworthy are the slightly elongated mesityl C—B bonds at 1.617 A (over those in Mes2BMe at 1.586 A) and the pronouncedly shorter methylene C—B bond at 1.444 A. Moreover, the C2BCH2 core atoms lie essentially in a plane. All these data support the view of 54 as a borataethene, just as structure 52a would imply. 

Oxcarbazepine has mood-stabilizing effects similar to those of carbamaz-epine, but with milder side effects, no autoinduction of metabolizing enzymes, and potentially fewer drug interactions. There are fewer data supporting its efficacy than there are for carbamazepine s efficacy. 

The simplest of all of the homoaromatics is the homocyclopropenium cation [2], This species was first invoked as an unusually stable intermediate by Applequist and Roberts (1956) to explain the reactions of methylene cyclobutenes with electrophiles. Since that time a wealth of studies has provided data supporting the special stability of the monohomocyclo-propenium cation (Story and Clark, 1972 Paquette, 1978). The parent cation and several simple derivatives have been examined by a variety of techniques including the convincing, direct H and 13C NMR observation... 

The cyclic stability (data are not shown) was also tested. After 2000 cycles, there is only a loss of 7 % in the acidic medium. This supports our view that N-doped carbons possess a significantly improved chemical stability. 

Stability data that did not support the expiration date Subpotency... 

Failure of stability data to support expiration date. Failure of drug to dissolve properly... 

In the sections that follow, we are going to describe a few representative examples of how histone variability (histone variants and their post-translational modifications) can affect nucleosome stability and folding. This data supports the notion that while some of this variability may be exclusively used to provide an informational code [121,123,165] it can also have important implications for structural aspects involved in the highly dynamic nature of the chromatin fiber. 

Solvent changes would be expected to result in changes in complex stability, especially where cations are strongly solvated in one solvent (e.g. Li+, Na+, Mg2+, Ca2+ in water) but not in another. The available data support this supposition, as seen in Table 14 where log K values for... 

Despite overwhelming data supporting the efficacy of ECT treatment for major depression, marked variation in the extent and pattern of its usage continues. Use of ECT declined in the 1970s but then appeared to stabilize or increase in the 1980s (J. W. Thompson et al. 1994]. ECT is used far more commonly in private hospitals than in public institutions and is more commonly administered to older patients and to women. Its more common administration to women may be the result of higher rates of depression in women (J. W. Thompson et al. 1994]. Olfson et al. [1998] similarly reported that ECT is used more often in white persons, those with higher incomes, and the elderly. 

Lithium Versus Anticonvulsants. A number of trials have also compared lithium to various anticonvulsant mood stabilizers such as VPA and CBZ ( 83, 99, 100). The results will be discussed in more detail in the sections on these specific agents. In general, lithium has been found to be comparable, but some data support better efficacy for agents such as VPA and CBZ in certain subgroups (e.g., mixed states, rapid cyclers). It is not clear, however, whether these agents have the same antisuicidal effects as lithium. 

A storage statement for the finished API should be prepared in compliance with the national and regional requirements. The established retest period, which is supported by the stability data, should be displayed on the certificate of analysis (COA) and as appropriate on the container label also. 

Long-Term and Accelerated Stability Data Show Little Change over Time and/or Variability Under this scenario, the proposed retest period or shelf life can be up to one and a half times as long as but not more than six months beyond the period covered by long-term data without the support of statistical analysis. 

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