1 General Controls
All activities from receipt till approval or rejection of materials should be described in one or more procedures. Materials must be purchased against agreed specifications.
Suppliers of critical materials, defined on the basis of the impact of the material on the API, should be evaluated and approved by the quality unit. The evaluation can be based on
- historical experience with the supplier,
- on a questionnaire,
- checking/comparing own analytical results (for e.g. three batches/shipments) with those on the suppliers Certificate of Analysis and / or
- an audit done by a person authorized by the purchasing company.
Audits are not required as per current GMP and should only be considered in case of (very) critical materials or as a result of e.g. deviations observed. Other useful information can include the reputation of the supplier within the industry and the availability of certificates such as ISO-9000 certificates. The evaluation and approval process should be described in a procedure, taking into account some or all these possibilities. This includes the fact that the name and address of the manufacturer of a critical material must always be known. A change of the source of a critical material should be handled according the Change Control procedure.
2 Receipt and Quarantine
Before acceptance of incoming materials the package should be checked visually. The materials should be sampled, tested and released. As long as the product is not released it must be held under quarantine; this can be realised in different ways e.g. separate areas or through a validated computer system. These systems or others may also be used to identify the status of the material.
Incoming stock materials should be released before mixing them with the existing stock. This new stock should get a new code.
Non-dedicated tankers should be released for use to prevent cross-contamination. Ideally, a cleaning certificate should be provided with each supply. If no such certificate can be provided, an audit of the cleaning procedure of the suppliers and/or transport company is recommended.
As in the factory, large storage containers and possible appendages should be identified appropriately.
3 Sampling and Testing of Materials
At least an identity test should be done on each incoming batch of material except in cases where this can negatively influence the safety or health of the co-workers. In this case a visual check of the containers and a certificate of analysis are sufficient. If the raw material is made by the same company and the product is transferred e.g. by pipes or containers from one plant to the other, re-testing at the point of use is not necessary, provided mix-ups are rigorously excluded by the design and set-up of the facilities. The release of such raw material can be delegated to the producing plant.
The suppliers of critical materials should be qualified according to what is mentioned under 7.1, including full in-house testing of at least three batches. After qualification of these suppliers batches may be released based on a certificate of analysis and an identity test. To check the reliability of the certificate of analysis full in-house testing should be performed at regular intervals according to the company procedures. The purpose of these analyses is not only to check compliance with the specifications, but also to verify the reliability of the data provided by the supplier.
The suppliers of non-critical materials don't need to be qualified and the materials may be released based on an identity test and a certificate of analysis or a certificate of compliance/conformity.
Samples taken from incoming materials must be representative for the batch and the sampling method should be described in a procedure taking into account the number of containers of raw material and specify the size and number of samples, the technical aids to be used and possible quality related information. Sampling should be done in an environment that prevents cross-contamination. The containers from which samples are taken should be properly identified (see figure 1).
Figure 1 Contents of the records in accordance with ICH Q7A
Content of test records
- Records of samples obtained: Name and origin of the material, batch number or other unambiguous coding, date of sampling and sample receipt, sample quantity
- Details of all test methods used.
- Details of weight or measures used for the related test
- Data or cross references to the preparation and testing of reference substances, reagents and standard solutions
- Complete record of all raw data generated during individual tests, in addition to graphs, tables, and spectra with identity of the tested material respectively batch to which the data refers
- Record of all calculations performed (including, e.g. units of measure, conversion and equivalence factors)
- Statement of the test results and comparison with acceptance criteria
- Date and signature of person executing the tests
- Data and signature of a second person who checks the records for accuracy, completeness, and compliance with established standards
Materials should be stored in a way that the quality of the raw material can not be negatively influenced taking into account light, time, temperature and humidity. Sufficient space should be available in the warehouses to allow efficient movements without damaging the packaged materials as well as to allow for cleaning. It is good practice to store the product at sufficient distances from walls.
Ideally, the floor of the warehouses should be lightly sloped to avoid stagnating water.
Materials stored in fibre drums, bags or boxes should be stored off the floor e.g. on pallets. Materials (e.g. in steel drums) may be stored outside if their identification remains guaranteed and if the product is not adversely affected by such storage conditions. Before opening these containers they should be cleaned appropriately.
All materials should be sampled and analysed (with the exception of hazardous and highly toxic substances). If supplier qualification is performed, an identity test may be sufficient. In sampling, any risk of contamination/cross contamination should be excluded. Sampled containers have to be labelled. For solvents, a certificate documenting the last cleaning of the truck and an identity test of the solvent are minimum requirements before unloading takes place. Outside storage areas are permitted as long as the materials stored there, are resistant to temperature and are packed and labelled in a manner that withstands the effects of weather.