Quality Risk Management for Facilities, Equipment and Utilities 134 Quality Risk Management as Part of Materials Management 135 Quality Risk Management as Part of Production 136 Quality Risk Management as Part of Laboratory Control and Stability Studies 137 Quality Risk Management as Part of Packaging and Lag 137 GLOSSARY 138
60. Filling should be carried out as soon as possible following production. Containers of bulk product prior to filling should be sealed, appropriately labelled and stored under specified conditions of temperature. 61. There should be a system to assure the integrity and closure of containers after filling. 62. The capping of vials containing live biological agents must be performed in such a way that ensures that contamination of other products or escape of the live agents into other areas or the external environment does not occur. 63. For various reasons there may be a delay between the filling of final containers and their labelling and packaging. Procedures should be specified for the storage of unlabelled containers in order to prevent confusion and to ensure satisfactory storage conditions. Special attention should be paid to the storage of heat labile or photosensitive products. Storage temperatures should be specified. 64. For each of production, the yield of product should be reconciled with that expected from that process. Any significant discrepancies should be investigated. Quality control 65. Inprocess controls play a specially important role in ensuring the consistency of the quality of biological medicinal products. Those controls which are crucial for the quality (e.g. virus removal) but which cannot be carried out on the finished product, should be performed at an appropriate stage of production. 66. It may be necessary to retain samples of intermediate products in sufficient amount and under appropriate storage conditions to allow repetition or confirmation of a batch control. 67. may be a requirement for the continuous monitoring of data during a production process, for example monitoring of physical parameters during fermentation. 68. Continuous culture of biological products is a common practice and special consideration needs to be given to the quality control requirements arising from this type of production method.
ANNEX 12 USE OF IONISING RADIATION IN THE MANUFACTURE OF MEDICINAL PRODUCTS Ionising radiation may be used during the manufacturing process for various purposes including the reduction of bioburden and the sterilisation of starting materials, packaging components or products and the treatment of blood products. There are two types of irradiation process: Gamma irradiation from a radioactive source and high energy Electron irradiation (Beta radiation) from an accelerator. irradiation: two different processing modes may be employed: (i) Batch mode: the products is arranged at fixed locations around the radiation source and cannot be loaded or unloaded while the radiation source is exposed. (ii) Continuous mode: an automatic system conveys the products into the radiation past the exposed radiation source along a defined path and at an appropriate speed, and out of the cell. Electron irradiation: the product is conveyed past a continuous or pulsed beam of high energy electrons (Beta radiation) which is scanned back and forth across the product pathway. 1. Treatment by irradiation may be carried out by the pharmaceutical manufacturer or by an operator of a radiation facility under contract (a "contract manufacturer"), both of whom must hold an appropriate manufacturing authorisation. 2. The pharmaceutical manufacturer bears responsibility for the quality of the product including the attainment of the objective of irradiation. The contract operator of the radiation facility bears responsibility for ensuring that the dose of radiation required by the manufacturer is delivered to the irradiation container (i.e. the outermost container in which the products are irradiated). 3. The required dose including justified limits will be stated in the marketing authorisation for the product.