Raw materials testing

Raw materials are normally accepted as being of useable quality based on two pieces of evidence. One is a certificate of analysis (COA) supplied by the supplier. This COA will often contain only analytical tests that are considered to have an impact on process robustness. This is probably one of the biggest variables causing lack of process robustness and therefore variability in both drug substance and drug product manufacture. 

Both types are used commonly in the pharmaceutical industry. In an at-line assay, samples are taken and analysed either by transmission/transflectance NIR if liquids, or reflectance if solids. The spectra generated are then used to build identification libraries. These hbraries must include the normal variation found in a good raw material distribution. Using these libraries, correlation or conformity 

These systems have shown themselves to be capable of identifying raw materials which are variable enough to cause downstream processing problems even though the more sensitive but more specific traditional types of analyses have found the materials to be acceptable. Often this approach is taken further and a prediction model developed whereby a qualitative model, using conformity or correlation algorithms checks the identity (ID) then a quantitative model uses the same data to predict a value of actual physical parameters such as moisture, concentration, and even particle size [4]. 

These systems are available with Ex rating for using in hazardous areas, although fibres up to 100 m long mean the actual spectrometer and control PC can be housed away from the area, possibly in a non-zone rated area. 

Release testing of raw materials or drug substances must be performed before they can be used for manufacturing a batch of the product. Assay and ordinary impurity determinations are usually performed by HPLC methods. However, when a reference standard for the active ingredient is not available, assay by titration is the method of choice. 

In the HPLC drug substance methodology, it is advantageous to have a different sample concentration for the assay and in-process impurity determinations. The impurity method should consist of sufficiently high concentration of the test sample such that the impurities at 0.05% levels will have sufficient 

When impurity reference standards are available only in limited quantities, relative response factors (RRFs) to the active ingredient can be used to quantitate impurity concentrations. RRFs can be determined spectrophotometrically by comparing the molar absorptivity of the impurity to that of the active component. However, in our experience, RRFs determined by HPLC by comparing peak area responses of the impurity to those of the active ingredient have been more accurate than those determined by spectrophotometric method. 

TLC methods can also be used for the determination of in-process impurities in drug substances. TLC methods are only semiquantitative when visual comparison of the size and intensity of spots is performed. Quantitative measurements are possible by means of densitometry or fluorescence measurements. The spots can also be carefully removed and dissolved in a suitable solvent for spectrophotometric measurement. 

Monograph tests such as those for water, residue on ignition, chloride, sulfate, and heavy metal content are performed as part of the release testing of a bulk drug substance (API). 

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Are raw material test results saved at least one year ... 

The company was a private label manufacturer of home maintenance and personal care products. Its laboratory would be involved with new product development, evaluation of raw materials, testing of competitive products, and quality control. Laboratory personnel would also be responsible for chemical safety in the plant and for proper waste disposal. 

Therefore, roles and responsibilities of the transfer exercise need to be discussed, clearly articulated, agreed and documented, including who does what and when. These roles and responsibilities should include availability of plant time (including shift cover), raw material testing time frames, OOS responsibilities and reporting, analytical testing time lines. 

P.J. Gemperline and L.D. Webber, Raw materials testing using soft independent modeling of class analogy analysis of near infrared reflectance spectra, Anal. Chem., 61, 138-144 (1989). 

Raw materials (tests, methods and specifications) Audit of the data submitted for CDER review in the application is a Field responsibility. CDER chemists are responsible for the scientific review of the associated data, evaluations of the adequacy of the submitted data, and ultimate approval of the tests, methods, and specifications established for the raw materials in the application. 

Process challenging and characterization reports that contain a full description of the studies performed Development batch record Raw material test methods and specifications... 

Lot-to-lot differences in the purity of the therapeutic agent must be considered when evaluating in-process and finished-product test results. In addition to potency such qualities as particle size distribution, bulk density, and source of the material will be of interest. Such information should be available from the raw material test reports prepared by the quality control laboratory for each lot of material received. The physical characteristics of the excipients should not be overlooked, especially for those materials with inherent variability. Metallic stearates is a classic example. In such instances, the source of supply is desirable information to have available. 

In general the quality control procedures for products obtained through biotechnology are very similar to those routinely used with traditional pharmaceutical products in areas such as raw material testing, documentation of process control, and aseptic processing. The fundamental difference is in the type of methods used, so as to determine the product s identity, uniformity, and purity. In the quality control of products obtained through recombinant DNA technology, it is necessary to employ validated tests for the final and intermediary products to ensure the elimination of undesirable impurities. 

Various types of validation generally required in biopharmaceutical manufacturing include process validation, facility and equipment validation, analytical method validation, software validation, cleaning validation and expression system characterization. Combined with other elements of cGMP, including lot release testing, raw material testing, vendor quality certifications, and vendor audits, the quality of product can be consistently assured. 

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