Thursday, June 11, 2009
2. Good manufacturing practices for pharmaceutical products (GMP
2.1 Good manufacturing practice is that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization. GMP rules are directed primarily to diminishing the risks, inherent in any pharmaceutical production, that cannot be prevented completely through the testing of final products. Such risks are essentially of two types: cross-contamination (in particular by unexpected contaminants) and mix-ups (confusion) caused by false labels being put on containers. Under GMP:
(a) all manufacturing processes are clearly defined, systematically reviewed in the light of experience, and shown to be capable of consistently manufacturing pharmaceutical products of the required quality that comply with their specifications;
(b) critical steps of manufacturing processes and any significant changes made to the processes are validated;
(c) all necessary facilities are provided, including:
(i) appropriately qualified and trained personnel;
(ii) adequate premises and space;
(iii) suitable equipment and services;
(iv) correct materials, containers, and labels;
(v) approved procedures and instructions;
(vi) suitable storage and transport; and
(vii) adequate personnel, laboratories, and equipment for in-process controls under the responsibility of the production management;
(d) instructions and procedures are written in clear and unambiguous language, specifically applicable to the facilities provided;
(e) operators are trained to carry out procedures correctly;
(f) records are made (manually and/or by recording instruments) during manufacture to show that all the steps required by the defined procedures and instructions have in fact been taken and that the quantity and quality of the product are as expected; any significant deviations are fully recorded and investigated;
(g) records covering manufacture and distribution, which enable the complete history of a batch to be traced, are retained in a comprehensible and accessible form;
(h) the proper storage and distribution of the products minimizes any risk to their quality;
(i) a system is available to recall any batch of product from sale or supply;
(j) complaints about marketed products are examined, the causes of quality defects investigated, and appropriate measures taken in respect of the defective products and to prevent recurrence.
3. Quality control
3.1 Quality control is the part of GMP concerned with sampling, specifications, and testing and with the organization, documentation, and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor products released for sale or supply, until their quality has been judged to be satisfactory. Quality control is not confined to laboratory operations but must be involved in all decisions concerning the quality of the product.
3.2 Each holder of a manufacturing authorization should have a quality control department.1 The independence of quality control from production is considered fundamental. The quality control department should be independent of other departments and under the authority of a person with appropriate qualifications and experience, who has one or several control laboratories at his or her disposal. Adequate resources must be available to ensure that all the quality control arrangements are effectively and reliably carried out. The basic requirements for quality control are as follows:
(a) Adequate facilities, trained personnel and approved procedures must
be available for sampling, inspecting, and testing starting materials, packaging materials, and intermediate, bulk, and finished products, and where appropriate for monitoring environmental conditions for GMP purposes.
(b) Samples of starting materials, packaging materials, intermediate products, bulk products and finished products must be taken by methods and personnel approved of by the quality control department.
(c) Test methods must be validated.
(d) Records must be made (manually and/or by recording instruments) demonstrating that all the required sampling, inspecting, and testing procedures have actually been carried out and that any deviations have been fully recorded and investigated.
(e) The finished products must contain ingredients complying with the qualitative and quantitative composition of the product described in the marketing authorization; the ingredients must be of the required purity, in their proper container, and correctly labelled.
(f) Records must be made of the results of inspecting and testing materials
and intermediate, bulk, and finished products against specifications; product assessment must include a review and evaluation of the relevant production documentation and an assessment of deviations from specified procedures.
(g) No batch of product is to be released for sale or supply prior to certification by the authorized person(s) that it is in accordance with the requirements
of the marketing authorization. In certain countries, by law, the
batch release is a task of the authorized person from the production
department together with the authorized person from the quality control department.
(h) Sufficient samples of starting materials and products must be retained to permit future examination of the product if necessary; the retained product must be kept in its final pack unless the pack is exceptionally large.
3.3 The quality control department as a whole will also have other duties, such as to establish, validate, and implement all quality control procedures, to evaluate, maintain, and store the reference standards for substances, to ensure the correct labelling of containers of materials and products, to ensure that the stability of the active pharmaceutical ingredients and products is monitored, to participate in the investigation of complaints related to the quality of the product, and to participate in environmental monitoring. All these operations should be carried out in accordance with written procedures and, where necessary, recorded.
3.4 Assessment of finished products should embrace all relevant factors, including the production conditions, the results of in-process testing, the manufacturing (including packaging) documentation, compliance with the specification for the finished product, and an examination of the finished pack.
3.5 Quality control personnel must have access to production areas for sampling and investigation as appropriate.