Product file preparation method

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... 

When there is already an existing Preparation Instruction then a referral can be made to this information in the product file. When the preparation is prepared on the basis of in-house decisions and expertise, the considerations which have led to the specific activities are recorded in the file, including the specific work order, the choice of equipment, or the considerations which have led to the inclusion of certain in-process controls. The description of the preparation method must give the pharmacist an overview on the process and should enable him to assess whether a modification might have impact on the quality of the final product. Also it might enable him to trace the critical preparation steps where in-process controls might be in place. 

Here a copy of the batch preparation record of the diclofenac sodium 12.5 mg suppositories could be included in the product file. Additional information may be given to explain the reasons for the choice of the excipients, the melting temperature of the hard fat base, the choice of the preparation method, the determination of overages, and of the number of suppositories that are expected to be rejected during production, etcetera. 

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. 

The product file should contain information on how the finished product will be analysed. For a standardised preparation the controls are defined in the file, with reference to the control methods or analytical techniques. If analysis is performed internally, the analytical instruction should be included. When analysis is not performed on every batch, the frequency of testing should be defined with the reasons for the choices that have been made. 

This part of the product file contains information about the validation of the preparation process and the method of analysis. It gives the rationale for the method of preparation, with validation data and any changes that have been carried out, and describes, where applicable, the background for the quality specifications of the preparation. 

Part II relates to the quality of the product and gives details of its chemical, pharmaceutical and biological testing. Data should be provided in respect of qualitative and quantitative particulars of the constituents, description of the method of preparation, control of starting materials, control tests on intermediate products, control tests on the finished product and stability tests. In cases where the active ingredient is made by a manufacturer other than the applicant or the product manufacturer, some of the information required in Part II may be presented in a separate file, the Drug Master File, to maintain the confidential nature of the synthetic process. 

In May 1922, the University of Toronto filed a patent on insulin for no other reason than to prevent the taking out of a patent by other persons. When the details of the method of preparation are published anyone would be free to prepare the extract, but no one could secure a profitable monopoly. Soon thereafter, the University of Toronto and Lilly began a collaboration, sometimes rocky, to produce insulin for wider clinical use. George Walden, a chemist at Lilly, developed novel production methods that simplified production and further improved lot-to-lot consistency by the Fall of 1922. Lilly began to market... 

The classical method for preparing hydroquinone is based on the oxidation of aniline with manganese dioxide or sodium dichromate in sulfuric acid. The qui-none which is obtained as an intermediate is reduced to hydroquinone with iron filings in dilute hydrochloric acid. This process, which is still used e.g. in India and China, is characterized by the simultaneous production of large amounts of manganese or chromium and iron salts, together with ammonium sulfate. For this reason, oxidative cleavage of p-diisopropylbenzene similarly to phenol synthesis was developed for the production of hydroquinone. 

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