It is our policy to always use and maintain the following procedure for production, Packaging, sampling, handling, storage, and delivery of product.
In order to prevent mix-ups or cross contamination, it is our policy to always provide raw materials testing, in-process control, and clean production and prefer to use dedicated equipment for special reactions.
1.1 Raw material testing
·Testing of each batch of a raw material against specified characteristics (e.g.appearance, identity, content)
·alternative: check of the certificate of the manufacturer or supplier
·usage of the material only after the release of the batch
·labeling of the drums or containers (label "released" or "rejected")
1.2 In-process control
·Sampling at critical process steps
·check of the completeness of the reaction
·usage of validated analytical methods and qualified equipment
·documentation of the results and comparison with the quality of the finished product
Clean production
- Clean production is a way of designing products and manufacturing processes in harmony with nature ecological cycles. It aims to eliminate toxic wastes and inputs and ultimately promotes the judicious use of renewable energy and materials.
- Using dedicated equipment for special reaction
- Making the production line and reaction process clean, re-circulates
ecologically safe materials and solvents, manage and control all the production procedure according to SOPs, especially for the distillation, drying and packaging step.
2.1 Homogenization of the product batch
·Before the packaging of the product batch, the material must be homogeneous Otherwise different drums of one batch could have different properties.
·Homogenization is possible by mixing of the whole batch in a vessel by stirring
2.2 Packaging and labeling
·drums or containers must be clean
·visible check of the inside of the drums or containers with a torch
·labeling before or immediately after the filling with product name, batch number, name of the manufacturer
·immediate closage of the containers to avoid contamination
·no mixing with other product batches after filling-danger of contamination with the wrong product/no homogeneity of the batch
·storage of the containers in designated areas: "before sampling"--"released material"-- "rejected material"
2.3 Production batches, crude material
·Drums or containers, which contain crude material of earlier production steps, must be labeled in the same way with:
Product name
Batch number
in order to prevent the contamination of products with other materials by mixing up drums which are not labeled.
3.1 Testing of instruments
·The functionality of all analytical instruments has to be tested before they are used for
the analysis of products. The tests have to be performed in regular periods, e.g. every
month. The test should be documented.
·A useful test for a gas chromatograph is the analysis of a standard sample, which
contains a pair of peaks, which is hard to separate. If the separation of the peak pair becomes worse, the column has to be changed. Another possibility is a standard sample which contains one by-product in a concentration near the specification limit. The function test is positive as long as the by-product is found in the right concentration.
·A label on the instrument must show clearly, that the last instrument testing was done, and when the next test has to be performed. If the date for the next test is expired, the instrument can’t be used for analyses until the instrument test was performed.
3.2 Validation of methods
·Analytical methods should be accurate, precise, selective, linear over the measuring range and robust against small variations in the performance. This should be tested and documented before the method is used for the testing of product batches.
·Precision: one sample is analyzed 6 times. The standard deviation of the results is calculated.
·Accuracy: a defined amount of by-product is added to a sample. The theoretical content of the by-products is calculated and compared to the content determined with the method.
· Selectivity: the major product must be detected beside by-products, e.g. peaks in the chromatogram must be separated to the base-line.
· Linearity: different amounts of a by-product are added to a sample. The detected signal in the gas chromatography must correlate linearly to the calculated content of the by-product in the samples.
· Robustness: the effect of small variations in the performance of the analysis on the analytical result must be tested, e.g. variations in:
sample weight
injection volume
gas flow velocity
oven temperature
different instruments
different laboratory worker
3.3 Documentation of analytical results
· All analytical raw data, print-outs of chromatograms or work sheets with analytical data filled by hand should be stored for a defined period, e.g. one year.
· The documents should contain at least the following data:
name of the product
batch number or other sample identification number
in case of solutions made: original sample weights
identification number of the analytical instrument
date and signature of the employee
4.1 Homogeniety of the material to be sampled
To get a representative sample of a given amount of material, the homogeneity of the product is most important. This can be achieved by stirring the whole batch in a vessel. If a batch is filled in 2 or more drums, small portions of samples must be taken out of some of the drums. These small samples are mixed completely in a steel bowl to one representative sample for the batch. The number of drums which are opened for sampling can be for example X where X is the total number of drums.
If the material is solidified, it isn’t homogeneous. During crystallization, impurities remain in the liquid phase while very pure product is crystallizing. Therefore, the concentration of the impurities is not the same at every point of the container or drum. The material must be melted before sampling.
Another possibility is to grind and mix the whole batch after crystallization. In this case, sampling of the solid material is possible.
4.2 Sampling of liquid material
·Sampling out of the reaction vessel after homogenization: filling of the sample bottle from an outlet at the bottom of the vessel.
·Sampling of containers with a sampling tube: thin glas tube with small open ends, as long as the height of the containers.
·Representative samples: the tube is inserted into the container while both ends are open. The liquid material flows into the tube while the tube is sinking to the ground of the container. The upper end of the tube is closed (e.g. with the thumb) and the tube with the sample is taken out of the container.
·Sample from the bottom of the container (important to detect solid particles or a second liquid phase in the material): the tube is inserted into the container while the upper end is closed (e.g. with the thumb). When the lower end reaches the bottom of the container, the upper end is opened and the material flows from the bottom into the glas tube. When the tube is filled, the upper end is closed and the tube is taken out of the container.
4.3 Sampling of solid material
·The material must be homogeneous to get a representative sample.
·Sampling with a steel sampling tube: the tube is inserted diagonally into the container, bag or sack. If the material is hard, a hammer may be used, to insert the tube. The tube is turned around and then taken out of the container. To prevent the material from falling back into the container, the steel tube may be equipped with a swing check value at the tip of the tube.
4.4 Sampling devices
·All devices for sampling, like sampling tubes or spoons, must be cleaned with a suitable solvent and dried after each sampling.
·If a series of batches of one product is to be sampled, the sampling devices do not have to cleaned after each batch.
4.5 Sampling work sheets
· the sampling should be documented on work sheets, which contain at least the following data:
Name of the product
Batch number
Number of containers or drums
Amount of material taken
Name of the employee and his signature with date
4.6 Labelling of samples
· The samples should be labeled with at least the following data:
Name of the product
Batch number
· The samples should be labeled before the sampling is done. Otherwise the sample bottles and the batches could be mixed up.
· In order not to mix the samples, a unique sample identification number is useful. Samples might be identified by the date of the sampling and the batch number, but this doesn’t work if two or more samples are taken of one batch at one day. One possibility is an additional suffix to the batch number, if more samples are taken on one day.
· For the safety of the employees, the sample bottles should be labeled with safety symbols (toxic, corrosive, harmful, inflammable, etc.)
5.1 Written standard operation procedures (SOP)
·Every step in production which is relevant for the quality must be described in a written standard operation procedure (SOP), so that every worker knows how to do in the right way. These SOP’s must be clear and easy to understand for everyone. The workers have to be trained in using the SOP’s. If a new release of a SOP is issued, all old issues must be destroyed.
5.2 Analytical methods
· Written analytical methods should contain the complete information for the employees in the laboratory to perform the analysis:
Sample preparation
Description of the equipment
Instrument parameters
Formula for the calculation of results
Typical illustration, e.g. chromatograms, titration diagrams
· Only authorized copies of the analytical methods should be in the lab. Old methods must be replaced by new methods if a new issue is released.
In order to ensure delivery of a product in the same condition we received and delivered it, it is our policy to always provide methods and means of handling that prevent damage or deterioration.
In order to prevent damage or deterioration of product, it is our policy to always provide secure storage areas or stock rooms pending use, or delivery. Appropriate methods for authorizing receipt and the dispatch to and from such areas shall be stipulated.
To detect deterioration, it is our policy to always assess the condition of product in stock at appropriate intervals.
In order to assure an undamaged product is delivered, it is our policy to always arrange for the protection of the quality of product after final inspection and test.
It is also our policy, where contractually specified, to extend this protection to include deliver to destination.