Specifications product file

Acceptance by FDA headquarters of specifications in the submission does not necessarily mean the FDA field office will accept them. The FDA field office during the PAI will check for appropriate development data to support filed specifications and ensure that these specifications are realistic. The submitted specifications should be supported with reliable and reproducible data and be sensitive and discriminating so that changes in raw materials or products can be detected. 

For products that are prepared extemporaneously at a regular basis or even for a limited stock, a product specific documentation (product file) is needed. This will include specifications, instructions, and records but also a pharmaceutical assessment of safety data, toxicity, biopharmaceutical aspects, stability, and product design. The product file should also include a product review as soon as a product is used repeatedly or over longer periods. 

When several documents related to the same product are bundled, it is called a product file. The product file is basically a collection of informatiOTi, instructions, records, investigation results etcetera oti a specific product. The product file is further discussed in Sect. 33.8. 

Before a prescription with a request for a pharmacy preparation can be approved, it has to be decided whether there is a specific clinical need for it. When defining the place in therapy, part of the assessment is the risk that is presented to the patient or a patient group both from receiving the preparation and from not receiving the preparation because it would not be available [3]. The risk should be estimated on the basis of a documented risk assessment (see Sect. 2.2.3) and the outcome of the assessment is recorded in the product file. 

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. 

The quality requirements are described in a separate section of the product file. These quality requirements include the specifications during preparation (in process controls), immediately after preparation (release specifications) and that at the end of shelf life of the product (shelf-life specifications). The specifications must be relevant to the respective dosage form and should be chosen in a such a way that they characterise the product quality within strict limits, while simultaneously ensuring that sufficient margin is left so that small batch-dependent variations can be accepted. 

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. 

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. 

Gaussian includes a facility for automatically generating a starting structure for a transition state optimization based upon the reactants and products that the transition structure connects, known as the STQN method. This feature is requested with the QST2 option to the Opt keyword. Input files using this option will include two title and molecule specification sections. The facility generates a guess for the transition structure which is midway between the reactants and products, in terms of redundant internal coordinates. 

The enzymatic transformation of natural products is by for file most attractive option. In this approach, it can be envisaged that sterols, which are relatively abundant, may be selectively modified to produce desired products. Hie diversity of enzyme activities, their reaction specificity, regiospecificity and stereospedfidty are all features which could contribute to carrying out the desired changes. This does not mean, however, that transformations using enzyme systems are simple. Nevertheless, biotransformations have become of vital importance in the production of steroids. 

In what is being called the most far-reaching overhaul of European Union environmental policy ever, the European Commission released a draft policy proposal on May 7 that, if enacted, would require virtually all manufacturers of chemicals to provide risk assessments and other information regarding products they sell or ship into the EU. Chemicals would also have to be registered with the EC and many downstream users of products that contain chemical entities would have to file paperwork as well. The Registration, Evaluation and Authorisation of Chemicals, or REACH, proposal would apply to approximately 30,000 new and existing chemicals, and test data would have to be developed on some 5000 specific chemical entities, many of which have been commonly used for decades. EUROPEAN COMMISSION... 

The use of any dye, harmless or otherwise, to color or stain a food in a manner whereby damage or inferiority is concealed is specifically prohibited by law. The use in food for any purpose of any mineral dye or any coal-tar dye, except those coal-tar tyes hereinafter listed, will be grounds for prosecution. Pending further investigations now underway and the announcement thereof, the coal-tar dyes hereinafter named, made specifically for use in foods, and which bear a guarantee from the manufacturer that they are free from subsidiary products and represent the actual substance the name of which they bear, may be used in foods. In every case a certificate that the dye in question has been tested by competent experts and found to be free from harmful constituents must be filed with the Secretary of Agriculture and approved by him" (21). 

Finally, new developments in zeolite catalyst and adsorbent manufacture will be outlined in the form of a survey of recent open and patent literature. Patents are extensively cited as reference materials for this chapter however no effort is made to identify specific manufacturing techniques actually used by any particular company to manufacture zeolites or any catalytic or adsorbent products. This is because there is no way to determine whether manufacturing patents are practiced as is or whether further refinements have been accomplished subsequent to the filing of the patents that may be held by specific companies as trade secrets. 

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