In this article we will discuss about the four main departments of pharmaceutical industries. The departments are: 1. Good Manufacturing Practice 2. Good Laboratory Practice 3. Quality Control 4. Quality Assurance.
Department # 1. Good Manufacturing Practice (GMP):
Good Manufacturing Practice (also called ‘current Good Manufacturing Practice’, cGMP’) is a part of Quality Assurance this ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use as required by the marketing authorization or product specification.
Additionally, GMP requires that all manufacturing and testing equipment has been qualified as suitable for use, and that all operational methodologies and procedures (such as manufacturing, cleaning, and analytical testing) utilized in the drug manufacturing process have been validated (according to predetermined specifications), to demonstrate that they can perform their purported function(s).
GMP is concerned with both production and quality control. Requirements of GMP ensure that:
(a) All manufacturing processes are clearly defined, systematically reviewed in the light of experience and are shown to be capable of manufacturing medicinal products of the required quality consistently as per recommended specifications.
(b) Validation is required for their manufacturing processes.
(c) All necessary facilities including qualified and trained personnel, adequate premises and space, suitable equipment and services, correct materials, containers and labels; approved procedures and instructions and suitable storage and transport facilities may also be provided for carrying out GMP.
(d) The instructions and procedures are to be written in an instructional form in clear and unambiguous language. The operators should be trained and the records must be maintained during manufacturing. This shows that all the steps related to defined procedures were taken into consideration. Thus, the quantity and quality of the product remain the same in all the concerned batches.
If any significant deviations occur, it must be recorded and investigated. Similarly, records of manufacturing including distribution enable the complete history of a batch. This is retained in a comprehensible and accessible form. The distribution (wholesaling) of the products should also minimize any risk to its quality.
The system must be available to recall any batch of product, from sale or supply. If any complaint lodged about marketed products, the causes of quality defects should be investigated and appropriate measures can be taken so that the defective products must not be produced in future.
GMP is a good business tool which helps to refine both compliance and performance in manufacturing company. GMP requirements are largely of common sense practices which will help the manufacturer so as it moves towards a quality approach using continuous improvement, Fig. 19.2 shows the creation and maintenance of a GMP lifestyle in a company to begin with set up of standards of performance.
These include GMP regulations and other standards which are necessary for any company. All the relevant departments in the company must have trained personnel of GMP and other standards.
In different countries there are different regulatory authorities that enforce to apply the GMPs such as Food and Drug Authority (FDA) in the United States, the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom, the Korea Food and Drug Administration (KFDA) in the Republic of Korea (South Korea), the Ministry of Health in Iran, India and Pakistan.
Each of the inspectorates carry out routine GMP inspections to ensure that drug products are produced safely and correctly; additionally, many countries perform Pre-Approval Inspections (PAI) for GMP compliance prior to the approval of a new drug for marketing.
The regulatory agencies of different countries like the FDA in the US are authorized to conduct unannounced inspections. Some inspections may be scheduled. FDA routine domestic inspections are usually unannounced, but must be conducted according to 704(A) of the FD&C Act (21USC374). Courts have held that any time the firm is open for business reasonably for an inspection.
Department # 2. Good Laboratory Practice (GLP):
The laboratory premises and equipment should meet the general and specific requirements for Quality Control (QC) areas. The personnel, premises, and equipment in the laboratories should be appropriate to the tasks imposed by the nature and the scale of the manufacturing operations.
(i) Documentation:
Laboratory documentation should follow the standard principles. An important part of this documentation deals with Quality Control. The major requirements of QC department are: specifications for the laboratory, sampling procedures of the item, and testing procedures (including analytical worksheets and/or laboratory notebooks).
Specifications:
A Quality control laboratory must follow their work procedures according to a specified protocols given in different pharmacopeias e.g. BP, USP, etc.
(ii) Sampling:
The sampling taking should be done in accordance with approved written procedures. The method of sampling, the equipment to be used, the amount of the sample to be taken and any other type of instructions the type and condition of the sample container besides precautionary measures especially with regard to the sampling of sterile or noxious materials must be considered. The instructions for the cleaning and storage of sampling equipment should also be mentioned.
(iii) Testing:
The testing procedure comprises of analytical methods. The analytical methods should be validated. All testing operations described in the marketing authorization should be carried out according to the recommendation. The results should be recorded and checked to make sure that they are reproducible.
The tests performed should be recorded and the records should include the important data such as:
(a) Name of the material or product and, where applicable, dosage form,
(b) Batch number and, where appropriate, the manufacturer and/or supplier,
(c) References to the relevant specifications and testing procedures,
(d) Test results, including observations and calculations, and reference to any certificates of analysis,
(e) Dates of testing,
(f) Initials of the persons involved in testing,
(g) Initials of the persons verified the testing and the calculations and
(h) A clear statement of release or rejection of the product (or other status) and the signature of the designated responsible person with date.
All the in-process controls including those made in the production area by production personnel should be performed according to methods approved by Quality Control. Special attention should be given to the quality of laboratory reagents, volumetric glassware, solutions, reference standards and culture media. All the items should be prepared in accordance with written standard protocols.
Department # 3. Quality Control (QC):
Quality Control (QC) is concerned with sampling, specifications and testing as well as the organization, documentation and release of the product procedures (Fig. 19.3). This ensures the necessary and relevant tests carried out for the release of products. The product to be released for sale or supply should be carried out only after checking their quality.
Quality Control is not confined to laboratory operations, but it is involved in all decisions which concern the quality of the product. The independence of Quality Control from production is considered fundamental to the satisfactory operation of Quality Control.
The basic requirements of Quality Control are as below:
(a) Adequate facilities, trained personnel and approved procedures must be available for sampling, inspecting and testing starting materials, packaging materials, intermediate, bulk, and finished products, and where appropriate monitoring environmental conditions for GMP purposes should be done.
(b) Samples of starting materials, packaging materials, intermediate products, bulk products and finished products are taken by personnel according to the methods approved by Quality Control.
(c) The test method should be validated.
(d) Records are made, manually and/or by recording data on-line. This should demonstrate that all the required sampling, inspecting and testing procedures were actually carried out. Any deviations from the recommended norms should be recorded and investigated.
(e) The finished products contain active ingredients (a.i.) complying with the qualitative and quantitative composition, their storage in proper containers must be done. The containers must be labelled.
(f) Inspection and the date of testing of materials, intermediate, bulk, and finished products should be formally assessed. The products deviations from specified procedures must be checked.
(g) No batch of product is released for sale or supply prior to certification by a qualified person, which is in accordance with the requirements of the marketing authorization.
(h) Sufficient reference samples of starting materials and products are retained to permit future examination of the product, if necessary. The product is retained in its final pack unless exceptionally large packs are produced.
Department # 4. Quality Assurance (QA):
Quality Assurance is a wide ranging concept which covers all matters individually or collectively that influence the quality of a product. It is the sum or total of the organized arrangements made with the object of ensuring the medicinal products are of the quality required for their intended use.
Therefore, Quality Assurance includes GMP. In a pharmaceutical production process, quality assurance is involved in several activities such as: purchasing, dispatching, warehousing, operational protocols, manufacturing, training, quality control, validation and packaging.
A quality assurance is considered by merging a series of actions. These actions collectively ensure product quality. As a result, the quality assurance system must establish specific activities before the start of production.
This also includes the control factors and product evaluation before formation of final product. The system of Quality Assurance for the manufacture of medicinal products should ensure that the products are designed and developed in a way that follows the requirements of GMP and GLP.
The production and control operations are clearly specified and GMP has been adopted. The managerial responsibilities must be clearly specified and arrangements made for the manufacture, supply and use of the starting, and packaging materials should also be taken care of. All necessary controls or intermediate products, and any other in-process controls and validations must be carried out.
Finally, the finished product should be correctly processed and checked according to the defined procedures. It is important to mention that the medicinal products are not sold or supplied before a qualified person certified each production batch in accordance with the requirements of the marketing authorization, and any other regulations relevant to the production, control and release of medicinal products.
The satisfactory arrangements exist to ensure that the medicinal products are stored, distributed and subsequently handled so that quality is maintained throughout their shelf life. On the other hand, there is a procedure for self-inspection and/or quality audit which regularly appraises the effectiveness and applicability of the Quality Assurance system.