Analytical documentation types

As shown in Figure 2, analytical documentation comprises a variety of analytical reports. The major types of analytical documentation are frequently... 

Although some documents are required only for NDA submission, the major types of analytical reports for regulatory submission are very similar for IND and NDA submissions. The differences in these reports for IND or NDA submission primarily concern the amount of data (e.g., number of batches, duration of stability studies) and level of detail. Also, the requirements for amendment of the information are different. The major types of analytical documents common to IND and NDA submissions are the following ... 

There are three major types of analytical documentation prepared to support investigational and marketed pharmaceutical products ... 

In general, specification and verification documents can be distinguished, while in practice mixed forms of both document types exist. Atypical specification document in the laboratory is a test specification, which contains all the requirements for carrying out the analysis starting with the mixing of solutions and reagents to the calculation of the analytical results. As a typical example of a verification document (record), a weighing record can be quoted. A mixed form of specification and verification documents is often found in test protocols that contain both requirements and relevant attestations [11]. 

This chapter highlights the important aspects of the analytical transfer processes as they relate to process, compliance, analytical data, and documentation. Types of method transfers and the timeline of transfer activities are discussed. The risk assessment prior to initiation of transfer activities is also described. The chapter describes content and utility of the transfer protocol and final report, as well as documents that govern analytical method transfers (i.e., SOPs and master plan). The importance of selecting appropriate method transfer acceptance criteria and use of statistical methods to evaluate results are described. The significance of the inclusion of an adequate level of detail in the methods, protocol(s), and other documents cannot be overly stressed. Last of all, the process for transfer of technical ownership of the analytical methods is discussed. Other chapters in this text should be consulted for elaboration on the various important facets of technical transfer, including method development, method validation, documentation, and stability. 

Quality Control. Reproducible production of perfumes requires careful quality control of all materials used as well as the compounding process itself. The use of analytical tools has iacreased over the years with their availability, but there can be no substitute for organoleptic evaluation. The human nose is far more sensitive than any analytical instmment for certain materials, yet it is also quite limited as a quantitative tool and is subject to fatigue. There are also weU-documented examples of specific anosmias ia iadividuals, ie, iaability to smell certain odor types, which is somewhat analogous to color-blindness. 

Hi) Specialized Analytical Methods. Analytical methods for metallic impurities are well documented and are not covered here. A major advance in the continuous monitoring of impurities in liquid sodium down to the lowest levels of detection has been the development of analysis using electrochemical cells. Oxygen analysis in sodium may be carried out using a cell of the type... 

The revised database holds over 23 000 analyte values for 660 measurands and 1670 reference materials produced by 56 different producers, from 22 countries. The database is restricted to natural matrix materials (i.e. made from naturally occurring materials, excluding calibration standards manufactured from pure chemicals). Information has been extracted from the relevant certificates of analysis, information sheets, and other reports provided by the reference material producers. As a general rule, the authors have only included in the compilation reference materials for which a certificate of analysis or similar documentation is on file. Information included in the survey is on values for measurands determined in reference materials, producers, suppliers, the cost of the materials, the unit size supplied, and the recommended minimum weight of material for analysis, if available. The new searchable database has been designed to help analysts to select reference materials for quality assurance purposes that match as closely as possible, with respect to matrix type and concentrations of the measurands of interest and their samples to be analyzed see Table 8.3. 

In contrast to many other validation protocols, the description of the NMKL validation process starts with the protocol of planned validation. This protocol should include, e.g., the needs of the client, available equipment, the chemical form in which the analyte occurs (i.e., in pesticide analysis the residue definition), matrix types, the availability of reference materials and the working range. Consequently, an extra paragraph is dedicated to the requirements for the documentation of validation results, which refers to the rules in Section 5.4.4 of EN 45001 (amended by ISO 17025). 

To diagnose the surface blemish problem several analytical techniques were employed. First, the samples were photo-documented. Since an aesthetic problem is by definition a problem with the visual appearance of an item, it is important to ascertain if all the defects are different or of the same nature. With close inspection, the sun visor arms were found to contain two distinct types of defects. Figure 1(a) shows what was called the Type A defect and Figure 1(b) shows the so-called Type B defect. These images were acquired using a stereomicroscope coupled with a digital camera. 

The linearity of a method is defined as its ability to provide measurement results that are directly proportional to the concentration of the analyte, or are directly proportional after some type of mathematical transformation. Linearity is usually documented as the ordinary least squares (OLS) curve, or simply as the linear regression curve, of the measured instrumental responses (either peak area or height) as a function of increasing analyte concentration [22, 23], The use of peak areas is preferred as compared to the use of peak heights for making the calibration curve [24],... 

This chapter covers the different types of documentation found in an analytical laboratory. These include the documents which are part of the management system and those dealing with the activities in specific areas of the laboratory. The control of documents is also covered. There are sections on the production and management of records. Finally, there is a brief description of what is meant by the accreditation of opinions and interpretations. 

It may seem unnecessary to have audits especially when there seem to be so many different types of audit. However, in spite of all of the documented procedures there are problems that can arise in analytical laboratories due to changes in staff, procedures, equipment, sample type and number of samples. For a laboratory to provide a consistent standard of quality in the face of all of these regular operational changes, Quality Audits need to be carried out. Audits will identify the problems which are expected to emerge, and provide a system to put them right. 

The impact of the release of liquid products on the environment can, in part, be predicted from knowledge of the properties of the released liquid. Each part of an ocular liquid product from petroleum has its own set of unique analytical characteristics (Speight, 1999, 2002). Since these are well documented, there is no need for repetition here. The decision is to include the properties of the lowest-boiling liquid product (naphtha) and a high-boiling liquid product (fuel oil). For the properties of each product (as determined by analysis) a reasonable estimate can be made of other liquid products, but the relationship may not be linear and is subject to the type of crude oil and the distillation range of the product. 

The use of HPLC to analyze biogenic amines and their acid metabolites is well documented. HPLC assays for classical biogenic amines such as norepinephrine (NE), epinephrine (E), dopamine (DA), and 5-hydroxytryptamine (5-HT, serotonin) and their acid metabolites are based on several physicochemical properties that include a catechol moiety (aryl 1,2-dihydroxy), basicity, easily oxidized nature, and/or native fluorescence characteristics (Anderson, 1985). Based on these characteristics, various types of detector systems can be employed to assay low concentrations of these analytes in various matrices such as plasma, urine, cerebrospinal fluid (CSE), tissue, and dialysate. 

You have your methodology both verified and validated as required for measurements needing a high level of confidence. But, you must also assure that your analyst Is experienced In performing the type of analysis you need, that you have standards for the analytes available, and that you have a written quality assurance plan that documents good laboratory practice. 

Trueness or exactness of an analytical method can be documented in a control chart. Either the difference between the mean and true value of an analyzed (C)RM together with confidence limits or the percentage recovery of the known, added amount can be plotted [56,62]. Here, again, special caution should be taken concerning the used reference. Control charts may be useful to achieve trueness only if a CRM, which is in principle traceable to SI units, is used. All other types of references only allow traceability to a consensus value, which however is assumed not to be necessarely equal to the true value [89]. The expected trueness or recovery percent values depend on the analyte concentration. Therefore, trueness should be estimated for at least three different concentrations. If recovery is measured, values should be compared to acceptable recovery rates as outlined by the AOAC Peer Verified Methods Program (Table 7) [56, 62]. Besides bias and percent recovery, another measure for the trueness is the z score (Table 5). It is important to note that a considerable component of the overall MU will be attributed to MU on the bias of a system, including uncertainties on reference materials (Figures 5 and 8) [2]. 

Although a thorough validation cannot rule out all potential problems, the process of method development and validation would address the most common ones. Examples of typical problems that can be minimized or avoided include interferences that coelute with the analyte in liquid chromatography (LC), a particular type of column that no longer produces the separation needed because the supplier of the column has changed the manufacturing process, an assay method that is unable to achieve the same detection limit after a few weeks, or a quality assurance audit of a validation report that finds no documentation on how the validation was performed. 

---