Drug product analytical method

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. 

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. 

Drug product Components, composition, specifications and analytical methods for inactive components, manufacturers, methods of manufacture and packaging, specifications and analytical methods for the drug product, stability. Methods validation package Environmental assessment Field copy certification... 

The specifications for drug substance, drug product, packaging components, excipients, and so on will be established based on sound technical justification, using a continuously expanding experience base that includes information on process, product, analytical methods, stability of drug substance and produces), packaging components, and so on. 

The administration of some drugs for prophylactic and enhanced production purposes requires a period of withdrawal prior to slaughter of the animals and suitable analytical methods to ensure that their products are acceptable as food (Table... 

Analytical methods and specifications must be established and validated so as to define and control the quality and purity of the raw materials, intermediates and the finished product. For many standard chemical raw materials, the development of specifications will not be necessary as they are already published in US and European pharmacopoeia (for example, standards for water, organic solvents and various excipients). The ultimate objective of these activities is to be able to manufacture the drugs required for clinical trials in accordance with good manufacturing practice (GMP). 

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. 

Dr. Perry G. Wang is currently a principal scientist at Teleflex Medical. His interests include analytical method development and validation, medicated device products, and environmental engineering. His expertise focuses on high-throughput analysis of drugs and their metabolites in biological matrices with LC/MS/MS. 

For any new excipients, APIs or drug products (where new does not necessarily mean novel, but new to the receiving site) there are additional testing criteria, e.g. supplier audits, third-party contract laboratory audits, analytical method transfers, sample management/tracking, etc. For those key excipients, where there is on-site historical experience, it still behoves both parties to check whether the local grade/supplier used by the CMO is equivalent to that used by the supplier (Worsham, 2010). There are many examples of differences in excipient physical properties, e.g. particle size, which have been attributed to different excipient sources that could ultimately impact on the performance of those excipients in formulated products (Frattini and Simioni, 1984 Dansereau and Peck, 1987 Phadke et al., 1994 Lin and Peck, 1994). 

Table 1. Pre-defined Analytical Method Transfer Acceptance Criteria for API and Drug Product (adapted from Agut et al., 2011)...

As described in the following chapter, there are many biopharmaceutical applications of protein assays. Assigning the protein concentration for the drug substance, drug product, or in-process sample is often the first task for subsequent analytical procedures because assays for purity, potency, or identity require that the protein concentration be known. Hence it is typical for several different methods to be employed under the umbrella of protein concentration measurement, depending on the requirements of speed, selectivity, or throughput. The protein concentration is valuable as a stand-alone measurement for QC and stability of a protein. However, protein concentration methods provide no valuable... 

In the development of new biopharmaceutical molecules, there is a constant need for analytical methods that provide critical information in areas that range from early characterization to routine analysis of approved products. Past experience indicates there are few projects in drug development that can be addressed by standard analytical procedures. Even well-established techniques often have to be modified to better suit the analysis of new samples. For this reason, a broad range of techniques is already an integral part of laboratories in the biopharmaceutical industry. 

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