Product file formulation

Product files for pharmacy preparations are described in Sect. 33.8. National formularies such as FNA (see Sect. 39.4.5) and NRF (see Sect. 39.4.2) entail the product and process design of a large number of standard pharmacy preparations. These formularies contain the description of the formulations and method of preparation, as well as elaborate elucidations on them. Many of these elucidations reflect the QbD ideas about documentation of the design process, friformatimi about product quality, efficacy, and safety is published in those formularies or in other clearly related sources information leaflets for the patient or clinical informatimi booklets for physicians. 

In the product file aU documents relating to a particular pharmacy preparation are brought together, including data on pharmacotherapy, the considerations which led to the choice for a certain formulation, preparation method and quality requirements of the product. It provides background... 

This section of the product file comprises all the details of the formulation and the preparation method and forms the central part of the product file. In general, this section should describe the details and considerations about ... 

In addition to the formulation the method of preparation is described in the product file. The process is explained with all the preparation steps (unit operations) in chronological order, including the quantities of active substances and excipients that apply to a particular batch size. Also the safety of the preparation process and the safety of the... 

For products described in a pharmacopoeia, the official specifications can and should be used for the product file, with referral to the official source. The same applies to preparations from standard formulatimis, in which quality requirements are included. For in-house formulations, the quality requirements have to be set by an appropriately competent person internally. Useful information can be found in the formulatimi or validatimi studies. The results of stability studies may be useful when setting the quality requirements for the product, because the premise is that a preparation should comply to the quality requirements throughout the whole shelf life. An overview of the applicable quality requirements, including supporting information, has to be included in the product file. In addition it should be specified how the packaging and labelling are checked, and how and with what analytical method the product quality is controlled. Additionally the validation of the analytical methods is included in this section of the product file. 

Software to predict the properties of formulated products is made more powerful by a recursive procedure which can use formulas stored in files as raw materials. Particular care must be taken with program flow control and data structures for the recursion to be effective. This paper illustrates these issues using an example derived from a working formulation system for coatings development. 

Figure 1 shows a flow chart for part of a recursive modelling procedure, illustrated in this paper, which accepts as input a formula consisting of constituent raw material codes or formula names, and quantities. The procedure retrieves property data for each raw material in order to perform the required calculations. When the procedure encounters a constituent that is a formulated product, it calls itself using that product as input. The output of the procedure consists of the calculated properties of the formula, including those properties of the formula that would be retrieved from data files for non-formulated or purchased raw materials. By returning this latter set of properties, the procedure can treat formulas as raw materials. 

The preclinical stage of drug development focuses on activities necessary for filing an IND/CTA. The completed IND/CTA contains information that details the drug s composition and the synthetic processes used for its production. The IND/CTA also contains animal toxicity data, protocols for early phase clinical trials, and an outline of specific details and plans for evaluation. Process research, formulation, metabolism, and toxicity are the major areas of responsibility in this development stage. Analysis activities that feature LC/MS primarily focus on the identification of impurities, de-gradants, and metabolites. 

Excipient and vendor selections can greatly influence the new drag development timeline, product performance, and acceptance of final products. Compendial excipients have composition consistent with monographs published in compendia such as USP-NF these are the better-characterized excipients. These excipients most likely possess desirable qualities and are preferred excipients for pharmaceutical formulations. Non-compendial excipients can also be used for drug products if they are supported by Type IV dmg master files (DMFs) in regulatory dossiers. Overall, a good excipient supplier should 29... 

Microcomputers, allow the optimizing of formulation cost or least-cost formulation. One method is to select from the formula file according to fluctuations in raw materials prices. The high number of formulas required can make this task quite difficult unless computers are used to sort out the least-cost formula. Production schedules and previous purchases of raw materials will also have to be considered (35). 

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