Pharmaceutical products quality control procedures

The lead time, for incorporation of enzymes as an adjunct in whatever form into commercial food processes, appears to be far longer than equivalent innovation lead times m non-food, or even pharmaceutical processes. The exception to this finding is that there are enzymes which play an important role in many analytical and quality control procedures in the food industry, without the use of which, for batch or continuous process monitoring, many product lines would not be possible. 

To gain FDA approval or license for marketing, a pharmaceutical product must be shown to be safe and effective for its proposed or intended use. The drug company or sponsor must also provide evidence to show that the processes and control procedures used for synthesis, manufacture, and packaging are independently validated to ensure that the pharmaceutical product meets established standards of quality. The overall effort from the inception of a new molecular entity and the establishment of analytical, scale-up, and quality control procedures, to the collection of safety and efficacy data for consideration by the FDA as part of an NDA or BLA, is called the drug development process. 

In general the quality control procedures for products obtained through biotechnology are very similar to those routinely used with traditional pharmaceutical products in areas such as raw material testing, documentation of process control, and aseptic processing. The fundamental difference is in the type of methods used, so as to determine the product s identity, uniformity, and purity. In the quality control of products obtained through recombinant DNA technology, it is necessary to employ validated tests for the final and intermediary products to ensure the elimination of undesirable impurities. 

All quality control procedures that are applied to nonradioactive pharmaceuticals are in principle applicable to radiopharmaceuticals. In addition, tests for radio-nuclidic and radiochemical purity must be carried out. Furthermore, since radiopharmaceuticals are short-lived products, methods used for quality control should... 

Peak purity analysis is also a useful addition to routine quality control procedures, especially in the analysis of pharmaceuticals and food products, for which contamination and quality of results are critical. 

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. 

The manufacturer must assume responsibility for the quality of the active pharmaceutical ingredients produced. The manufacturer alone can avoid mistakes and prevent mishaps by exercising adequate care in both production and control procedures. Full evidence of compliance with GMP should be given from the step from which the processes or the starting materials used have a critical influence on the quality of the active pharmaceutical ingredient This step should be determined in each individual case by agreement between the competent authority and the manufacturer. 

There should be a master formula setting out in writing the starting materials and packaging materials (quality and quantity), as well as detailed production and quality control procedures for each active pharmaceutical ingredient. Wherever posable, the master formula should be prepared for standard batch sizes. 

In vitro drug release studies have been employed as a quality control procedure in pharmaceutical production, in product development, etc. Sensitive and reproducible release data derived from physicochemically and hydrodynamically defined conditions are necessary however, no standard in vitro method has yet been developed. Different workers have used apparatus of varying designs and under varying conditions, depending on the shape and application of the dosage form developed. 

In terms of technological transfer, until March 2015, Farmanguinhos had donated for free 10 out of 21 technological dossiers for the production of specific pharmaceuticals, to include results from pharmaceutical equivalence tests, quality control procedures for APIs and other ingredients, manufacturing process specifications and test failure reports. The next steps for technological production are still under way and include ... 

If the product is to be used for pharmaceuticals the GMP rules must be obeyed during plant operation. All chemicals to be tested in clinical studies with humans must be prepared according to GMP. This leads to very detailed documentation since if you haven t documented it, you haven t done it . All procedures for manufacturing and changes in procedures are subject to approval by quality control departments. This decreases the flexibility in process development. Products that are contaminated too much must be reprocessed according to the GMP guidelines. All equipment to be used in the pilot plant must be validated before use. 

Pharmaceutical analysis procedures may be used to answer any of the questions outlined in Box 1.1 above. The quality of a product may deviate from the standard required but in carrying out an analysis one also has to be certain that the quality of the analysis itself is of the standard required. Quality control is integral to all... 

Vacancy chromatography has a number of applications areas in practice, none of which appear to have been extensively exploited. One particularly interesting application is that of quality control. If a particular product has a number of components present, and their relative composition must be kept constant as in, for example, a pharmaceutical product, Vacancy Chromatography can provide a particularly simple analytical procedure for quality control. The mobile phase is made up containing the components of the product in the specified proportions, but at a low concentration suitable for LC analysis. A sample of the product is dissolved in some pure mobile phase at the same total mass concentration as the standards in the mobile phase. A sample is then injected on the column. If the product contains the components in the specified proportion, no peaks will appear on the chromatogram as the sample and mobile phase will have the same composition. If any component is in excess, it will show a positive peak. If any component is present below specifications, it will show a negative peak. The size of the peak will provide an accurate measure of the difference between the sample and that of the required standard. 

Components are received and are quarantined in ABC Pharmaceutical Industries stores until all testing and certificate of analysis requirements are reviewed and have met the acceptance criteria set forth in manufacturing site standard operating procedures. When all acceptance criteria have been met, the components are released by Quality Control and are ready to be issued for production using the procedures specified in manufacturing site standard operating procedures. 

If you are in charge of quality control laboratories in manufacturing companies, it is important to distinguish between the variability of a product and the variability of the analysis. When analyzing tablets on a pharmaceutical production line, variability in the results of an analysis has two contributions from the product itself and from the analytical procedure. Your bosses are interested in the former, and you, the analyst, must understand and control the latter. It is usually desired to use methods of analysis for which the repeatability is much less than the variability of the product, in which case the measured standard deviation can be ascribed entirely to the product. Otherwise, analysis of variance can be used to split the total variance of duplicate results into its components (chapter 2). In the discussion that follows, the emphasis is on measurement variability, but the principle is the same, and the equations and methods can be used directly to obtain information about the product or manufacturing process. 

A fundamental objective of a computer system applied to automate a pharmaceutical GMP operation is to ensure the quality attributes of the drug product are upheld throughout the manufacturing process. It is therefore important that quality-critical parameters are determined and approved early in the validation life cycle. The exercise should be undertaken to a written procedure with base information from the master product/production record file examined and quality-critical parameter values and limits documented and approved for the process and its operation. In addition, the process and instrument diagrams (P IDs) should be reviewed to confirm the measurement and control components that have a direct impact on the quality-critical parameters and data. This exercise should be carried out by an assessment team made up of user representatives with detailed knowledge of both the computer system application and process, and with responsibility for product quality, system operational use, maintenance, and project implementation. This exercise may be conducted as part of an initial hazard and operability study (HAZOP) and needs to confirm the quality-related critical parameters for use in (or referenced by) the computer control system URS. 

Raw material specifications and their acceptable limits. All raw materials are tested before they are used in a pharmaceutical product. These materials must meet quality standards or meaningful specifications, and their limits must be set so that the use of unsafe, impure, and inefficacious materials will not be allowed in the product. The control labs will run the tests or have a contractor perform them, but QA will ensure that the lab procedures are properly followed and documented. Furthermore, QA will ensure that no raw materials were released improperly. 

The Japanese PAB notification no. 158 [19] and No. 660 [19a] detail the obligation of pharmaceutical manufacturers by defining the validation standards enforced from 1996 onward. The purpose of validation is presented as follows to validate that buildings and facilities of a manufacturing plant and manufacturing procedures, processes and other methods of manufacturing control and quality control yield anticipated results, and to ensure the constant manufacture of products of intended quality by documenting such procedures. ... 

---