Scientific Challenges

Each product that is developed must exhibit acceptable safety, efficacy, and stability profiles, each feature being built into the product through dosage form design based on sound scientific principles. However, the manner in which these are addressed and the additional challenge of residual drug remaining at the administration site must be taken into account when developing a dosage form for an animal. Safety aspects apply to both the user and the animal. Efficacy trials may involve many more participants compared with human trials, and must often encompass different breeds, seasons, and geographical locations to evaluate the effect of these on product efficacy. As mentioned before, the final design of the product must take into account the means by which the product will be administered to the animal by the end user. The maximum size of any veterinary delivery system, for example, may not be determined by the anatomical constraints of the animal, but rather by the physical dimension of the administration device. Thus the final dosage form can often be much smaller than the formulation scientist first envisages, resulting in lower dose-loading capacity and fewer capabilities of the delivery system than first imagined.

Chemical stability can be a major issue. Neither farm sheds nor farm vehicles (typical storage places for purchased veterinary pharmaceuticals) have cold storage facilities or even air conditioning, therefore assuming that a product can be stored below 20°C or in the fridge for the duration of its lifetime prior to administration is an unreasonable assumption. Dosage forms must therefore be stable to elevated heat conditions and hot/cold heat fluctuations. Where appropriate packaging must offer more than just physical protection, it is the formulation scientist's responsibility to determine and demonstrate if moisture protection needs to be addressed through relevant packaging, but this can add cost to the final product.

Physical stability is also an issue. Farmers do not have the time to premix individual doses of suspensions, nor constantly "shake the bottle" between administrations to some several hundred individual cows of their herd. Thus, for example, in the case of suspensions, the final product physical characteristics are often a balance between retardation of sedimentation and ease of flow to draw up into the syringe. Thus a critical evaluation of existing suspension products by a formulation scientist new to the field may draw false conclusions as to the need for an improved product based on ease of administration since there is more than pharmaceutical elegance involved in developing the perfect veterinary formulation. Indeed, a farmer is less interested in what the product looks like compared with its efficacy profile, ease of use, ease of administration, ease of removal, tissue residue profile, and time it takes to herd, administer, and release his animals back into the paddock. Veterinary formulation scientists may therefore trade off pharmaceutical elegance to improve other features, provided the efficacy and safety profile is acceptable and not altered during storage.

A final issue relating to veterinary dosage forms designed for long action is assurance of safety and efficacy after administration at the terminal end of its shelf life. Data is often generated to demonstrate that a drug product is stable under normal storage conditions for two years; however, a long-acting veterinary dosage form may be designed to deliver drug for up to six months. If such a product is purchased close to its accepted shelf life period, what assurances are there that this product will remain safe and effective when it is administered to the animal and becomes subjected to the biological environment of high moisture and elevated temperatures (40°C). This is an interesting problem, and maybe such delivery systems should be subjected to the normal shelf life storage conditions for two years, followed by a further period (dictated by the proposed duration of the product) of 40°C/75% RH. Such a procedure could assure both users and regulatory authorities alike that the product is safe and effective under label stated storage conditions, for the approved duration as stated on the label as well as after administration regardless of when the product is purchased within the label-approved shelf life period of the product. Acceptance limits may need to be proposed wider, but can be justified based on the demonstration of comparative efficacy and safety to freshly manufactured product.

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