Handling of materials
1. Handling of materials including aspects related to the receipt, identification, quarantine, storage, handling, sampling, testing and approval or rejection, shall be done in accordance with written procedures or instructions and recorded as appropriate.
2. Suppliers of materials used in the manufacturing of the active substance shall be approved by the quality unit after verifying the suitability thereof. In case of critical materials, qualification of the suppliers is required. The level of supervision shall be proportionate to the risks posed by the individual materials.
3. All materials shall be purchased in compliance with the relevant specification.
4. Where the supplier of a critical material is not the manufacturer of that material, the name and address of that manufacturer shall be known by the intermediate or active substance manufacturer.
5. Changes in the source of supply of critical raw materials shall be treated according to Chapter XIII.
Receipt and quarantine for incoming materials
1. Upon receipt, each container or grouping of containers of materials shall be examined visually for correct labelling, including for correlation between the name used by the supplier and the name used by the manufacturer, if these are different.
2. Damage to containers and any other problem (e.g. evidence of seal tampering or evidence of breaches of package integrity) that may adversely affect the quality of a material shall be investigated.
3. Incoming materials shall be physically or administratively quarantined immediately after receipt, until their release is authorised by a responsible person, after verification of compliance with the relevant specifications.
4. Before incoming materials are mixed with existing stocks (e.g. solvents or stocks in silos), they shall be identified as correct, tested, if appropriate, and released. Procedures shall be available to prevent discharging materials erroneously into the existing stock.
5. Whenever bulk deliveries are made in non-dedicated tankers, the absence of cross-contamination from the tanker shall be assured. Such assurance can be provided by means of one or more of the following elements:
—
a certificate of cleaning,
—
testing for trace impurities,
—
audit of the supplier.
6. Large storage containers, and their attendant manifolds, filling and discharge lines shall be appropriately identified.
7. Each container or grouping of containers with incoming materials shall be assigned and identified with a distinctive code, batch, or receipt number. That number shall be used in recording the disposition of each batch.
8. A system shall be in place to identify the status of each batch during receipt and quarantine.
Testing of incoming materials
1. At least one test shall be performed to verify the identity of each batch of incoming material. A supplier's certificate of analysis may be used in place of performing tests, provided that the manufacturer has a system in place to evaluate suppliers.
2. Supplier approval shall include an evaluation that provides adequate evidence (e.g. compliance history), that the manufacturer consistently provides material meeting the relevant specifications.
3. A full analysis shall be conducted on at least three batches of incoming material before reducing in-house testing of that material. That full analysis shall be performed at appropriate intervals and compared with the supplier’s certificates of analysis.
4. The reliability of certificates of analysis shall be checked at regular intervals.
5. By way of derogation from paragraph 1, processing aids, hazardous or highly toxic raw materials, other special materials, or materials transferred to another unit within the manufacturer’s control do not need to be tested if the supplier’s certificate of analysis is obtained, showing that those materials conform to established specifications. Visual examination of containers, labels, and recording of batch numbers shall contribute to establish the identity of those materials. The lack of on-site testing for those materials shall be justified and documented.
Sampling of incoming materials
1. Personnel in charge of taking samples shall receive training on the techniques and equipment for sampling, the risks of cross-contamination, precautions to be taken with regard to unstable or sterile substances, the need to record any unexpected or unusual circumstance as well as other aspects relevant to the implementation of the sampling procedures.
2. Samples shall be representative of the batch of material from which they are taken. The taking of samples shall be done in accordance with written procedures that describe at least the following:
(a)
the number of containers to be sampled;
(b)
which part of the container to sample;
(c)
the amount of sample to be taken from each container.
3. The number of containers to sample and the sample size shall be based upon a sampling plan that takes into consideration the following:
(a)
the criticality of the incoming material;
(b)
material variability;
(c)
compliance history of the supplier;
(d)
the amount of sample needed for analysis.
4. Sampling shall be conducted at defined locations and by procedures designed to prevent contamination of the material sampled and contamination of other materials.
5. Containers from which samples are collected shall be opened carefully and subsequently reclosed. They shall be marked to indicate that a sample has been taken.
6. Sample containers shall bear a label indicating the content, batch number, date of sampling and containers from which the samples have been taken.
Re-evaluation of materials
All materials shall be re-evaluated as appropriate to determine their suitability for use (e.g. after prolonged storage or exposure to heat or humidity).
Source: EUR-Lex (Publications Office of the EU), © European Union, reuse permitted under Commission Decision 2011/833/EU.
