Drug products development methods

Analytical Development of API and Drug Products. Early methods to support synthetic and formulation developments are often developed in the form of potency assay, impurities/related substance assay, dissolution, Karl Fischer, identity, chiral method, and content uniformity. These analytical methods are developed and validated in a fast and timely manner to support all phase II studies. 

Figure 3 shows that the use of a single analytical methods testing function is an important technical bridge between the API and the drug product development functions as the latter two move through the various stages of develop-... 

Stability studies during the IND phase provide not only assurance of the quality of clinical trial material but also the basis for the drug product development program. Stability data are used to evaluate different formulations, methods of manufacture, and container-closure systems, as well as to determine storage requirements, expiration dating periods, and specifications. 

An analytical method is a laboratory procedure that measures an attribute of a raw material, drug substance, or a drug product. Analytical method validation is the process of demonstrating that an analytical method is reliable and adequate for its intended purpose. Any method that is utilized to determine results during drug substance and formulation development will have to be validated. Reliable data for release of clinical supplies, stability, and setting shelf life can only be generated with appropriate validated methods. 

Determination of the skin flora (Other than on the hands). The development of new sampling techniques provides methods to study, qualitatively and quantitatively, the microbial flora of various parts of the body [15,16]. The panel encouraged utilization of these methods in the evaluation of topical antimicrobial drug products. The methods provide information that allows assessment of the... 

Surrogates are useful in the assessment of antimicrobial products, including antiseptics, provided they are standardized, reproducible, and have known predictive value. The methods proposed in the TFM, although standardized and reproducible, have not been validated to assess their clinical predictive value. In fact, none of the standardized surrogate methods used in antiseptic drug product development have been validated (TFM and ASTM reference). Thus, we are left to extrapolate from the premise that reduction of the microbial flora is a desired outcome, and if it is achieved, the product will be successful in the clinical setting. 

The field of co-crystals has elicited significant interest in the pharmaceutical industry recently with the potential to utilize this technology as means of enhancing physicochemical properties such as solubility and dissolution in addition to enhancements to particle properties that could aid drug product development,. e.g. improving both chemical and physical stability and indeed as a method to induce crystallization of materials that traditionally would have been isolated as an oil or an amorphous material. There is also considerable ongoing debate as to the theoretical definition of a co-crystal, how a co-crystal can be reliably synthesized, manufactured and characterized, coupled with the intellectual properties ramifications therein. This presentation will outline some of our recent research efforts (in-house external) into the synthesis of co-crystals, and will outline different techniques that can be utilized to characterize co-crystals. 

The aforementioned process will need to be repeated for a number of different solvents. Typically, the solubility will be observed in water, as well as a number of different aqueous solutions which are buffered to a standard set of pH values. This profile of pH versus thermodynamic solubility is one of the most important pieces of information that is needed throughout drug product development. The inflection point in this pH profile will be a good method to measure the pK of the material. An example of this technique is shown in Figure 1. 

There are three basic classes of dissolution methods, all three of which have a role to play in early phase drug product development. These three classes are... 

Our formulation development activities we developed both a biorelevant dissolution method, and a drug product release method. At this point in development, all of our formulation development activities are complete, making the biorelevant method less important. The formulation(s) is fixed, and we are now concerned with demonstrating that we can consistently manufacture batches of drug product. We will also want to show that the release characteristics of the dosage unit do not change on stability. Oiu" drug product release method will fulfill this role and will be the primary dissolution method, until the method conditions need to be revisited when in vivo data become available from om first clinical studies. At that time, the method should be revisited to evaluate how biorelevant our in vitro data are. 

In spite of the considerable progress in developing methods for total synthesis, this route to cephalosporins cannot compete with fermentation or penicillin rearrangement (see Sections 5.10.4.1 and 2) for the industrial production of cephalosporin antibiotics. While total synthesis does provide access to nuclear analogs not readily obtainable from fermentation products, none of the totally synthetic materials have displayed sufficient advantages to Warrant their development as new drug products (b-81MI51000). 

The previous chapters examined the process for the development and authorisation of a drug product containing a ne v active ingredient for human use. This represents the most arduous path to market for any medicinal product. This chapter proceeds to examine the process of bringing a veterinary medicinal product to market. While the process shares most of the principles that apply to human drugs, there are some additional features that are unique to veterinary products. These include methods of use and the requirement to evaluate vithdra val periods and maximum residue limits in food-producing species. 

Drug substance/drug product purity, potency, and other testing Drug substance/drug product stability testing Method development, validation, and transfer Drug product formulation development... 

Contracting out of activities previously only conducted in-house is already becoming quite common and will probably continue to develop. In the past a so-called full-service pharmaceutical company took direct responsibility for all the activities required for the formulation, manufacture, quality control, and regulatory approval of its drug products. Nowadays the use of specialist contract houses to perform activities such as formulation, analytical methods development, manufacture of clinical trials supplies, supervision of the assembly of an NDA, postmarketing surveillance, and even troubleshooting may be contracted for even by some of the largest companies. 

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