Drug products method

A typical validation protocol for a drug product method is discussed in detail next. 

When TLC is used to track a specified impurity in the drug substance, it is likely to be applied to the subsequent drug product method. A plate must be prepared to show that required levels of LOD and LOQ can be achieved for the specified impurity in the presence of excipients. This is known as a spiking experiment. The specified impurity is prepared and spiked into the vial of the drug product at different levels, then applied to the TLC plate to ensure it can be extracted to meet the requirement of LOD and LOQ. If no specified impurities are being tracked by TLC, this validation test can be excluded. 

Various strategies are pursued by pharmaceutical companies to extend the product life cycle. Under the Hatch-Waxman Act, patent term extensions are available for patented drug substances, drug products, method of use, and method of manufacturing to compensate for the time lost in the FDA s regulatory approval process. However, the limitations of the statute of the following aspects have to be considered ... 

Before the performance of method transfer activities involving protocols and acceptance criteria, it was customary for a receiving laboratory to repeat some or all of the validation experiments. This laboratory was thereby deemed to be qualified when the results were demonstrated to meet the acceptance criteria described in the validation protocol. The choice of validation parameter(s) depends highly on the type of method being transferred. For example, content uniformity assays to determine consistency of product potency depend heavily on the method and system precision. As a second example, a determination of trace impurities in an API could not be reproduced between two sites if their instruments did not yield similar limits of detection and/or quantitation. A detailed discussion on the rational choice of validation parameters that would need to be repeated by the receiving laboratory is beyond the scope of this chapter. The reader is referred to the method validation chapters by Wood (in-process methods) and Clarke and Bretnall (API and drug product methods) for additional information on this subject. 

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). 

For drug substances and drug products, applications for enantiomers and racemates should include a stereochemically specific identity test and/or a stereochemically selective assay. The choice of control tests should be based on the method of manufacture and stability characteristics and, in the case of the finished product, its composition. 

Methods of assessing the stereochemical integrity of enantiomeric drug substances and drug products should be included in the stability protocols for both, but stereoselective tests may not be required once it has been shown that racemization does not occur. 

Determination of the drug substance is expected to be enantioselective, and this may be achieved by including a chiral assay in the specification or an achiral assay together with appropriate methods of controlling the enantiomeric impurity. For a drug product where racemization does not occur during manufacture or storage, an achiral assay may suffice. If racemization does happen, then a chiral assay should be used or an achiral method combined with a validated procedure to control the presence of the other enantiomer. 

The quality module must contain information on the identity, characteristics, manufacturing methods, control, packaging and stability of both the drug substance and final drug product. The standard headings used to present this information are shown in Figure 6.2. 

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. 

This review of PCL and its copolymers is largely drawn from the nonpatent literature and focuses primarily on aspects relevant to drug delivery. Methods of polymerization are considered at some length because of the impact on polymer structure and morphology, which in turn determine the permeability and biodegradability of the product. 

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

The portal of drug entry The physical form of the drug product The design and formulation of the product The method of manufacture of the drug product Various physicochemical properties of the drug and excipients... 

Description of the methods, facilities, and controls used to prepare and distribute the drug product... 

The growth of generic prescribing and generic substitution will clearly increase the role and responsibilities of pharmacists in drug product selection. This movement will also stimulate in many regions of the world further debate about how bioequivalence should be quantified and when in vitro methods may, in some... 

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