Validation extemporaneous preparation

Such national formularies are good starting points for formulations as they may have been tested or supported by published or validated formulae. A secrnid example is the German Formulary (Neues Rezeptur-Formularium, see Sect. 39.4.2). In the UK, the Handbook of Extemporaneous Preparation (see Sect. 39.4.6) also lists a selectimi of 50 commonly used formulae, and the British Pharmacopoeia has a small number of formulatirMis detailed. The existence... 

An assay on separate capsules gives direct information on the mean content of active substance in the capsules and its variation between capsules. In pharmacy preparation such assays are usually performed during the validation of a formulation and during routine examination of large batches of standardised preparations. But for extemporaneous preparations in-process controls and non-destmctive end controls have to be sufficient. The requirements for the mean content and content uniformity of capsules are described in Sects. 32.4 and 32.7.2. 

When a pharmacist is to prepare an extemporaneous preparation for which no standard formulation exists, there is usually not much time for experiments and pilot batches. The risk assessment of the prescription should however be performed carefully (see Sect. 2.2). The preparation process should be validated on the level of dosage form and the preparation documentation (see Sect. 33.5), including the results of in-process controls, should be evaluated by the pharmacist before dispensing for use by the patient. 

Analysis of each batch will take too much time and money (excess active substance needed) to be an option for extemporaneous preparations. The qualification of operators for the preparation of capsules, by validation and monitoring may be feasible. This may lead though to specialisation of operators and thereby to a decrease of flexibility. 

In extemporaneous preparation, the mixing time in a mortar is frequently determined by visual assessment of the mixture after the procedure has been validated. Usually a mixing time of powders in a mortar should not be shorter than 3-4 min. For larger scale preparations the required mixing times have to be assessed by analysis and validated. Mixing times may differ quite a lot, depending on material properties, such as particle size, mixing ratio and volume of the powders. 

In separate sections the importance of choosing and defining relevant quality parameters to guarantee the required quality of the medicine is discussed. It is explicitly mentioned that stock preparations are generally tested more extensively than extemporaneous preparations. It is also mentioned that if it is not practical to perform tests on pharmacy preparations, for example because the batch is too small or because of the delivery time, other suitable methods may be used to guarantee that the required quality level is met. With this, the process validation has obtained an official position next to the end control of products. It should be stressed, however, that when tested at any point during the product shelf life the product must meet the specification in the monograph. 

Stock preparations are performed according to a standardised preparation instruction, an instruction that has been validated prior to use. This is called a Batch Preparation Instruction (BPI). Also for extemporaneous preparations, a standardised preparation instmction - a BPI - is preferred. However, often the operator has to follow a non-standardised preparation instmction that is less extensive, where no prior validations have been performed, see further Sect. 33.5. 

Preparations can be divided into stock preparations and extemporaneous preparations. In this chapter the focus is mainly on stock preparations. The principles described are equally applicable to extemporaneous preparations. However, the required extent of quality control and validation might be less in extemporaneous preparations due to the few affected patients and the need to deliver urgently (see also Sect. 21.6.3). 

Preparations differ in size and complexity. The scale may range from a tailor-made preparation for one patient to a (semi-)industrial production for thousands of patients. The complexity may range from the reconstitution of an authorised medicine to complex preparations from active substances and excipients. In this chapter we focus mainly on stock preparatiOTis. The principles described are equally applicable to simpler preparations such as extemporaneous preparations and even for reconstitution [4]. However, the extent of quality control and validation should be justified by risk assessment [5, 6 and Chap. 21]. 

A practical approach for the validation of non-standardised extemporaneous preparations may be ... 

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