Batches, selection

The main drawback in chiral separation methods using derivatized CDs is that these selectors are mainly available as complex mixtures that contain a large number of isomers differing in their degree of substitution, which may result in batch-to-batch selectivity differences.The use of pure single enantiomers or very reproducible mixtures is thus required to obtain reproducible and robust methods. 

In preparation of the documents for the CMC section, one of the first items to consider is the selection of a representative batch of the drug substance and the drug product for the NDA. Ideally, the representative drug substance batch selected was used to manufacture the representative drug product batch. This will provide a good and consistent data flow in the CMC section. 

Only one batch of drug substance or drug product needs to be tested during the development phase, and then the photostability characteristics (i.e., either photostable or photolabile) should be confirmed on a single final batch. This batch should be one of the three final batches used for regulatory submission. Batch selection should be based on the criteria outlined in the parent guideline for selection of batches placed on definitive stability (32). 

DRUG SUBSTANCE A. Developmental Stability Testing Batch Selection... 

Batches selected for stability studies should optimally constitute a random sample from the population of production batches. In practice, the batches tested to establish the expiration dating period are often made at a pilot plant that may only simulate full-scale production. Future changes in the production process may thus render the initial stability study conclusions obsolete. 

In adcfition to the information described in Section XI.B., the validation protocol should include the batch selection criteria and analytical data that will be evaluated to determine consistency of the process. 

Fig. 5.63 Strength-grain size relationship (a) and subcritical growth of radial indentation cracks (b) of sintered batches selected from Fig. 5.62. Straight lines are least squares fits. Strength ranking numbers associate specimens in (b) to batches in graph (a), numbers 1-3 are consistent with Table 5.2 and Fig. 5.62 [20]. With kind permission of Elsevier...

Tank capacity must also be considered when designing a winery. High-capacity tanks are of course economical, but tank size should not be exaggerated and should be adapted to the winery (50-350 hi). It is difficnlt to control the various steps in winemaking in vats containing over 350 hi. Tanks of limited capacity permit snperior batch selection and skin extraction dne to increased skin contact. The tank shonld be filled before the start of fermentation and for this reason the filling time should not exceed 12 hours. 

As it pertains to batch selection, site-specific stability has been the subject for discussion between FDA and industry. Site-specific means that stability batches are manufactured at the proposed manufacturing site. The site-specific stability is to assure that the batches used for expiration date determination will be representative of the batches made for commerce. Although site-specific stability testing has typically been implemented for years, it is not an absolute requirement from all authorities. It is recommended that the requirements for site-specific stability be determined for each country prior to initiation of the registration stability studies. 

A membrane-induced structure—reactivity trend, which may be exploited to achieve selective processes, was observed in polymeric catalytic membranes prepared by embedding decatungstate within porous membranes made of PVDF or dense polydimethyl-siloxane (PDMS) membranes. These photocatalytic systems are characterized by different and tunable properties depending on the nature of the polymeric microenvironment (Bonchio et al., 2003). The polymeric catalytic membranes prepared were used for the batch-selective photooxidation of water-soluble alcohols. Membrane-induced discrimination of the substrate results from the oxidations of a series of alcohols with different polarity, through comparison with the homogeneous reactions (Fig. 27.7). 

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