Adherence to this guiding principle of GMP/GLP has led to a considerable increase in the ratio of paperwork to practical work at the laboratory bench. Therefore, pre- printed forms are a very useful tool for ensuring that no essential parameters are for- gotten in the hustle and bustle of the daily routine. In the area of quality control of a pharmaceutical business enterprise, these forms can be designed individually to in- clude each testing parameter. All master copies ofauthorized forms must carry the stamp of the Quality Assurance department (usually “QA”). Copies of these are then used as working papers. The raw data sheets for TLC are thus only a part of the com- plete documentation for a substance (raw material) or product (proprietary pharma- ceutical product) to be tested. In hardly any of the forms, therefore, is there any refer- ence to the relevant testing procedure. The document number of the testing procedure is marked on a covering sheet (testing protocol), on which the complete scope of the testing is also recorded, classified according to parameters and pages.
Examples of raw data sheets for various TLC investigations are given below. Some of these forms were prepared specifically for the present book, and the space for the QA stamp therefore contains the author’s initials. All raw data sheets, also including those for IR and pH, have the same heading design to make it easier to complete using a PC.
The following comments may help to give a better understanding of the forms:
TLC Raw Data Sheet I(Document 5)
This form was designed specifically for routine analyses to test for the identity and pu- rity of large numbers of pharmaceutically active ingredients and intermediates. The samples are weighed out on an analytical balance with no printer. All operating proce- dures are given in a valid testing procedure.
The result is documented by placing a cross against the relevant parameter. This raw data sheet does not show whether the checker has actually seen the completed chromatogram or whether the formal documentation of this work has simply been au- thenticated!
Today the official guidelines within the pharmaceutical industry require the manda- tory use of a combination of balance and printer. For this reason the form is used only rarely.
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TLC Raw Data Sheet II(Document 6)
This too is a form for routine analyses. However, the instructions here can refer not only to in-house product-specific testing procedures (e.g. for proprietary medica- ments) but also to monographs of valid pharmacopoeias (DAB, Pharm. Eur., USP etc.) and other sources (e.g. DAC). Samples can be weighed out on analytical balances with printout facilities. The printed paper strips should include at least the date, the code number of the reference substance and the batch numbers of the samples. The image of the chromatogram obtained should be documented and the archive number should be recorded on the raw data sheet. The result is also recorded by placing a cross in the appropriate place. Here, the checker can at least inspect and assess the images of the chromatograms.
TLC Raw Data Sheet III (Document 7)
The original version of this form (see p. 213) was produced in 1988 in accordance with the present author’s instructions and was published in 1992 at a Merck Symposium [154]. Over the years, it has been modified to comply with more stringent require- ments. For example, the parameters “relative humidity” (following a recommendation of Nyiredy [26]) and “other evaluations” (which could refer, e.g., to video scan or radio TLC) were included for the first time in 1997. To give the user an example of a univer- sal type of form for TLC, the heading is given here in its original version, and the ex- planations below are listed.
Comments on the raw data sheet “Thin-Layer Chromatogram”
This form fulfills all the GMP/GLP requirements for the documentation of thin-layer chromatograms, and has been found to be highly satisfactory over the years, especially in method development. It is advisable to fill out this sheet before starting to apply samples to a plate.
The form is suitable for development work both before and after writing a new test- ing procedure, and for testing raw materials and finished products in accordance with a testing procedure that is already to hand. It can be used both for manual application and for application with the aid of the semiautomatic Linomat IV equipment. For other application equipment, appropriately designed forms should be used.
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Hints on filling out this form
1. The serial number of the chromatogram, which depends on the subject, is entered in the heading (e.g. 44).
2. The empty space with surrounding border is intended for the subject (substance, name of preparation etc.) and any necessary additional information, e.g. “LOD”
for limit of detection, “STLC” for sample chromatogram or “Stress samples” for samples subjected to “defined substance stress”.
3. Characterization of the sorbent (e.g. TLC-K60 WF254s), the article number and the manufacturer of the precoated layer (e.g. 16485 Merck) and the batch used (e.g.
08733902) are documented.
4. For coded precoated plates of the silica gel 60 type, the individual plate number is entered.
5. The composition of the “prewashing agent” and, if appropriate, its migration dis- tance are noted.
6. Prewashed plates are always activated (30 min, 120 °C); amino-modified silica gel layers, for example, are activated without prewashing (10 min, 120 °C).
7. Settings of the Linomat IV: start, spaces between lanes and lane widths in mm, ap- plication rate in s/ l.
8. The chamber type is noted: N for normal chamber (or DT-N for double-trough chamber, CAMAG), H for horizontal chamber (e.g. 5 × 5 cm, DESAGA), DC- MAT for automatic development chamber (Baron), ADC for automatic develop- ing chamber (CAMAG), etc.
9. To describe the state of chamber saturation (CS), “with” or “without” should be circled.
10. The composition of the solvent system in “ml”, the migration distance in “cm”, the development time in “min”, the ambient temperature in “°C” and the relative hu- midity in “%” should be given.
11. Information on the derivatization can be in the form of either reagent names (e.g. “Dragendorff”, “vanillin-sulfuric acid”) or a literature reference (e.g. “JFFW 1a/265” indicates the reagent in the Jork/Funk/Fischer/Wimmer Vol. 1a, p. 265:
2,5-dimethoxytetrahydrofuran-4-(dimethylamino)-benzaldehyde reagent).
12. In the “Documentation” line a cross is placed at the appropriate place, and when the images have been obtained the archive numbers are entered in the boxes be- low (at a later time in the case of films!).
13. If more than 12 lanes are used, the table can be continued on the back of the form.
14. The analyst enters the date of completion of the chromatogram and also his or her signature in the spaces provided, and any additional information sheets are also dated. The checker initials this form and the last of the additional sheets on com- pletion of all the documentation that applies to this plate (sheets with pasted-on photographs, attached scanner printouts, videoprints etc.).
15. Corrections to this form are made using a pencil of a different color so that the er- roneous entry remains legible even after it has been crossed out. The correction must be dated and initialed.
16. The sample preparation method and comments can be added to the back of this form.
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TLC Raw Data Sheet IV (Document 8)
This form was designed exclusively for stability samples of preparatory pharmaceutical products. In this case it should be assumed that a valid testing procedure is available, so that it is unnecessary to record the sample preparation method and the chromato- graphic conditions. Above all, it is important that the developed chromatogram should be checked for the possible presence of additional zones (AZs). The number and the intensity of each individual AZ must be documented.
TLC Raw Data Sheet V(Document 9)
It is explained in Section 8.5 “TLC Scanner Documentation” why it is necessary to provide a covering sheet for the “paper mountain”, giving the results in abbreviated form and documenting the number of added pages. The TLC Raw Data Sheet V (see p. 216) is the first page of this collection, and is followed by one page each on equip- ment parameters (type of sample application equipment, chamber type, method of evaluation and equipment with item number etc.), the weighing protocol of all refer- ence substances (inclusive of any correction calculations to give the weight of the an- hydrous substance) and the samples. The last two of these forms are not shown here for reasons of space.
Raw Data Pages and LIMS
Today in the industry Laboratory Information Management Systems (LIMS) are com- monly used. When a sample requiring TLC analysis is created in LIMS, the system au- tomatically creates the required links and prints all necessary raw data pages.
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Document 9