Quality control of raw materials In-process control

To minimize and eliminate these sources of variation which can cause product quality variation approaches such as material control, good manufacturing practice (GMP), in-process quality control (IPQC) and many other techniques, such as packaging control, automation and statistical sampling are employed.

Drug substance control:  Drug substances must meet the specifications previously established for it.  Moreover, the materials used in the manufacture and processing of drugs shall be identified, stored, examined, tested, handled and otherwise controlled.  Drugs generally are not absolutely pure, since they may contain substances that are by-products of the synthesis of products. Appropriate records should be maintained as to their origin, receipt, testing, and disposition and as to the assurance of their conformance to the appropriate standards of identity, purity, quality, strength, potency, and freedom of contaminants at time of use.

 Infact, control of raw materials whether active or inactive and of packaging and printed materials actually begins before purchase and is maintained by careful handling procedures throughout the manufacture of the packaged dosage form.  The quality control inspector performs appropriate visual examination of the incoming materials and then follows a prescribed sampling procedure to provide test material for laboratory evaluation.  The testing results submitted by the suppliers are compared and reviewed with those acquired by the quality control department of the drug manufacture.

Excipients control:  Excipients are components of the finished dosage form other than the therapeutic ingredient.  Although they are inert, they may influence the quality of a product owing to interaction with the drug substance affecting the physical properties of the dosage form or influencing the production process. To prevent such effects: ● Excipients should be examined carefully and critically for compliance with established standards. ● They must be supplied in clean and properly sealed containers. ● They should be inspected prior to laboratory testing. Labeling should be correct. The material should be packaged in the correct container. No obvious damage of the container in transit. Lot number should be stated.

Quality control procedures include: ● Sampling of raw materials - All incoming raw materials are initially quarantined and samples are taken and tested to ensure that the material meets strict purity guidelines. - This testing involves both microbiological and chemical testing, as is laid out in the relevant pharmacopeia (a reference book on the preparation of pharmaceuticals three are published British, United States and European).

● Final product checking ● Monitoring cleaning ● In-process checks The manufacturing staff carry out checks on such things as tablet weight and size at frequent intervals. At hourly intervals the quality control staff take samples to check for contamination and to ensure that composition is as expected. ● Final product checking Checking similar parameters to those measured during production. ● Monitoring cleaning When a batch of a certain drugs has been made, all equipment that has been used must be cleaned. When the next pharmaceutical to be made on that line is going to be different, this cleaning must be particularly through to prevent contamination. In this instance, after cleaning the QC staff take swabs off each piece of equipment and test them to see if they can detect the presence of the active previously used.

● The results of all these tests are recorded on the batch records for the pharmaceutical, as well as the name and batch number of the pharmaceutical made immediately prior on the same production line.  Raw material standardization is the only way for all the drug manufactures to produce the drugs in same quality and to maintain the uniformity.

Incoming raw material Store Sampling Identification Analysed Transfer Incoming raw material Store Sampling Identification Analysed Equipments Manufacture Purity testing Assessed and control of microbial contamination Finished products Inspected Representative samples analysed Documented

The ultimate goals of QC/QA programs are to assure that: ● The drug product contains the labeled amount (s) of the active ingredient (s), within the accepted tolerance limits. ●The ingredients (active or inactive) were of the acceptable pharmaceutical purity according to quality specifications as cited by drug compendia. ● The variation of drug levels between dosage units is minimized. ● The finished dosage forms should be of the highest possible purity i.e. no contamination. ● The ingredients in the finished dosage form are stable within specified time (shelf-time). ● The finished dosage form is therapeutically efficacious i.e. bioavailability studies or bioequivalency studies have been carried out properly in the research and development (R&D) phase.

 Good raw material specifications must be written in precise terminology and details of test methods, type of instruments and manner of sampling must be identified.  Table 27-1 lists general tests, limits and other physical or chemical data for raw materials related to identity, purity, strength and quality.  Table 27-2 presents the quality assurance monograph for acetaminophen, USP, as an example of a specific raw material quality assurance monograph.  The manufacturer physically inspects and assigns lot numbers to all raw materials received and quarantines them untill they are approved for use.  Each raw material is sampled according to standard sampling procedures and is sent to the quality control laboratory for testing according to the written procedures (Table 27-2).  If acceptable, it is moved to the release storage area, after being properly stickered to indicate the item number, name of material, lot number, date of release, reassay date and signature of the quality assurance inspector.

 It is retested as necessary according to an established schedule to assure that it still conforms to specifications at time of use.  Quality assurance personal should keep preservation samples of active raw materials that consist of at least twice the necessary quantity to perform all tests required to determine whether the material meets the established specifications. These preservation samples should be retained for at least 7 years.  Approved materials should be rotated so that the oldest stock is used first.  Any raw material not meeting specifications must be isolated from the acceptable materials, stickered as a rejection, and returned to the supplier or disposed of promptly.