Efficacy testing

The formulation scientist must be aware of interactions between preservatives and other components of a formulation that could compromise the efficacy of the preservative. For example, proteins can bind thi-merosal, reducing preservative efficacy. Partitioning of preservative into a micellar phase or an oil phase (in an emulsion) can also reduce the effective concentration of preservative available for bactericidal or bacteriostatic action. Preservative efficacy testing should be done on the proposed formulation to assure an effective preservative concentration. 

Where a large pack size is provided, it might be necessary to undertake more extensive in-use testing and/ or to restrict the in-use shelf life once the container has been opened. In addition to preservative efficacy testing the chemical stability of antimicrobial preservatives should also be investigated over the unopened and in-use shelf lives of the product. 

FIGURE 1.1. Attrition during the development of new molecules with a promise of therapeutic potential. Over the course of taking a new molecular entity through scale-up, safety and efficacy testing, and, finally, to market, typically only one out of every 9000 to 10,000 will go to the marketplace. 

Gad, S.C. (1998). Strategies and application of in vitro methods to the development of pharmaceuticals and devices. In Advances in Animal Alternatives for Safety and Efficacy Testing (Salem, H., Ed.). Taylor Francis, Philadelphia, PA, pp. 293-302. 

Design a safe dosage regimen for efficacy testing in adults, pediatric, or elderly. 

Determine the drug interaction potential when concurrent medications are administered, as well as food interaction, assess the enzyme induction potential, and assess the need for therapeutic drug monitoring during efficacy testing. 

The initial strategy for Phase I is to conduct a single-dose safety study in normal volunteers. The first trial demands close 24-hour supervision in a clinical setting. Ethical considerations may, however, demand that only patients be used, for example, when evaluating an anticancer agent with predictable toxicity. A repeat dose tolerance and pharmacokinetic study in normal or patient volunteers is then conducted for chronically administered drugs. These studies will provide the necessary safety information to support efficacy testing. 

Efficacy Testing of the Drug Targeting Device in the Liver... 

It was also essential to determine how effective bromethalin was against warfarin-resistant rats and mice. Such animals, whose resistance to anticoagulants had been determined by World Health Organization tests,(17) were subjected to a standard EPA choice feeding efficacy test with bromethalin at 0.005% in the treated diet. The results indicate (Appendix 6) that 90% of the animals were killed and that consumption patterns were similar to those observed in other choice tests. 

To date no guidelines are available for the efficacy testing of active substances, however, for biocidal products. Paragraph 52 of Annex VI states that testing should be carried out according to Community guidelines if these are available and applicable. Where appropriate other methods can be used e.g. 

In 1998, a CEFIC working group composed of industry experts from EPAS (European Producers of Antimicrobial Substances) and EPFP (European Producers of Formulated Preservatives) compiled a listing of over 200 relevant efficacy testing methods and around 100 of these were critically analysed in... 

In fact, the lack of appropriate efficacy methods is internationally recognised by the authorities and there is an OECD initiative to (i) improve knowledge on what methods are available for efficacy testing of the different biocidal product types, their validity and any problems they may have and (ii) identify gaps where new methods are needed. 

A sample of a standard calcium carbonate slurry was received from a large manufacturer in the USA. This sample was subjected to preservative efficacy testing according to the ASTM E 723-91 test protocol. Preservative treated samples were inoculated with a mixed bacterial inoculum containing organisms with a known tolerance or resistance to BIT (l,2-Benzisothiazolin-3-one). Untreated controls were included for reference purposes. The test procedure is outlined below. 

The authors wish to acknowledge the support of Cath Lewis and Lawrence Staniforth in performing the microbiological efficacy tests reported in this paper. 

The main objective of validation of an analytical procedure is to demonstrate that the procedure is suitable for its intended purpose. The procedures presented in this SOP provide basic guidelines for the validation of methods for microbiological assay, estimation of the number of microorganisms, detection of indicators of objectionable microorganisms, validation of preservative efficacy testing, and validation of the sterility testing and endotoxin test (LAL test). 

The objective is to provide standard procedure for performing the preservative efficacy test for nonsterile and sterile dosage forms. 

Product categories under preservative efficacy test (Table 1) Table 1 Product Categories... 

Media perform growth promotion test for all media used in preservative efficacy test... 

Efficacy Test on Wall (Sandwich Panel) (Coupons)... 

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