Bridging study

Figure C3.2.7. A series of electron transfer model compounds with the donor and acceptor moieties linked by (from top to bottom) (a) a hydrogen bond bridge (b) all sigma-bond bridge (c) partially unsaturated bridge. Studies with these compounds showed that hydrogen bonds can provide efficient donor-acceptor interactions. From Piotrowiak P 1999 Photoinduced electron transfer in molecular systems recent developments Chem. Soc. Rev. 28 143-50.

These situations are treated as completely new applications which should include an explanation of the decision to develop the enantiomer or racemate. Data on the existing racemate or enantiomer may be included where appropriate with bridging studies as necessary. 

The area of racemic switches where a single enantiomer is developed subsequently to a corresponding racemate which is already on the market has attracted much interest [7, 8]. A description of the preclinical and clinical development of dexketoprofen provides a detailed example of one of these racemic switches [21]. The regulations in Europe and the US both allow for the development of a single enantiomer from a racemate by the use of bridging studies between the old and new applications. One problem to be considered is how a company which was not responsible for the original development can provide equivalent data. 

PD 020 Vol. 6, Bridging study Randomised Tablet, 50 mg. 24 (12 drug. Patients with 2 weeks Ongoing ... 

NR Cutler, JJ Sramek. Scientific and ethical concerns in clinical trials in Alzheimer s patients the bridging study. Eur J Clin Pharmacol 48 421-428, 1995. 

If the vector is changed, a full safety evaluation may be required. However, if the changes are minor compared to the structure of a fully evaluated vector, it is appropriate for safety to be addressed by bridging studies. For example, if there is only a minor change on one of the condensation peptides of a nonviral, selfassembling vector, then some simple bridging work, rather than a full evaluation, may be appropriate. 

It is quite possible that a treatment may be initiated using, for example, intratumoral injections to deliver a gene, which may subsequently be administered systemically. As a considerable amount of relevant information will have already been generated to support the intratumoral route, this would be another case for doing bridging studies. Comparative distribution studies will help to identify how much more safety evaluation may be required. 

Data predominantly generated in one ethnic group to be used for registration in another may be acceptable in their entirety, or bridging studies may be required in the second ethnic population to determine if differences exist. ... 

The need for bridging studies depends on whether the medicine is ethnically sensitive or insensitive on the basis of the criteria discussed above. For example, if the product was metabolised through a route that displayed no genetic polymorphism, had a wide therapeutic index, a shallow dose-response curve and there were universally agreed endpoints to determine efficacy and safety, then no bridging studies would be needed. 

C Ang, W Luo, CR Kiessling, K McKim, R Lochmann, CC Walker, HC Thompson. A bridging study between liquid chromatography and microbial inhibition assay methods for determining amoxicillin residues in catfish muscle. J AOAC Int 81 33-39, 1998. 

Major CMC changes, including site changes, anticipated from phase 2 through the proposed NDA or BLA, ramifications of such changes, and appropriateness of planned comparability and/or bridging studies, if applicable... 

Studies necessary to support the change or modification from the listed drug or drugs (if any). Complete studies of safety and effectiveness may not be necessary if appropriate bridging studies are found to provide an... 

Before submitting the application, the applicant should submit a plan to the appropriate new-drug evaluation division identifying the types of bridging studies that should be conducted. The applicant should also identify those components of its application for which it expects to rely on the FDA s finding of safety and effectiveness of a previously approved drug product. The division will critique the plan and provide guidance. 

For different salts, acids, or bases of the same therapeutic moiety, where prior carcinogenicity studies are available (provided no significant changes in pharmacokinetics, pharmacodynamics, or toxicity) (When changes in exposure and consequent toxicity are noted, additional bridging studies may be used to determine whether additional carcinogenicity studies are needed)... 

Material production Evolution of production methods and appropriate bridging studies. 

Olah and co-workers represented the nonclassical structure as a corner-protonated nortricyclane (62) the symmetry is better seen when the ion is drawn as in 63. Almost all the positive charge resides on C-1 and C-2 and very little on the bridging carbon C-6. Other evidence for the nonclassical nature of the 2-norbomyl cation in stable solutions comes from heat of reaction measurements that show that the 2-norbomyl cation is more stable (by 6-10 kcal mol or 25 0 kJ mol than would be expected without the bridging.Studies of ir spectra of the 2-norbomyl cation in the gas phase also show the nonclassical stmcture. Ab initio calculations show that the nonclassical stracture corresponds to an energy minimum. ... 

Some properties of a drug or its class may make it insensitive to ethnic factors. This will make it easier for extrapolation to different regions and reduce the need for bridging clinical data. Properties that make it susceptible to ethnic influences see Table 18.1 will require bridging studies, sometimes of PK/ dynamics studies or safety and efficacy either or both. 

If the bridging study shows similarity to the dose-response study in safety and efficacy, this is usually sufficient, even if this study shows that a different dose is indicated. That is especially so if at that new dose (range) a similar safety and efficacy profile has been demonstrated. 

The ICH issued a further Questions and Answers Guidance (US Food and Drug Administration, 2004) to provide further explanations of when bridging studies may be required following six years of experience. 

---