Quality control of raw materialsIn-process control

IntroductionSources of Quality variation: The diversity of drugs and dosage forms produced, the size andcomplexity of the operation and varying processes andequipments employed differ from company to company. The manufacture of pharmaceutical products frequently involvesa series of successive processing operations and each of theseoperations can be expected to have some influence upon thequality of the finished product.The risk of error increases as the number of materials involved ina formulation becomes greater, the process becomes morecomplex and the operation becomes larger.

To minimize and eliminate these sources of variationwhich can cause product quality variation approachessuch as material control, good manufacturing practice(GMP), in-process quality control (IPQC) and manyother techniques, such as packaging control, automationand statistical sampling are employed.

Certain quality control measures should be taken which can becategorized in the following manner:Material control (drug substances, excipients, packaging materials,and printed supplies)

Drug substance control: Drug substances must meet the specifications previouslyestablished for it.Moreover, the materials used in the manufacture andprocessing of drugs shall be identified, stored, examined,tested, handled and otherwise controlled.

Drugs generally are not absolutely pure, since they may containsubstances 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 theirconformance to the appropriate standards of identity, purity,quality, strength, potency, and freedom of contaminants at time ofuse.

The physical, chemical and biological properties that characterizethe acceptable quality of the drug are established. Infact, control of raw materials whether active or inactive and ofpackaging and printed materials actually begins before purchase andis maintained by careful handling procedures throughout themanufacture of the packaged dosage form. The quality control inspector performs appropriate visualexamination of the incoming materials and then follows aprescribed sampling procedure to provide test material forlaboratory evaluation. The testing results submitted by the suppliers are compared andreviewed with those acquired by the quality control department ofthe drug manufacture.

control:Excipients Excipients are components of the finished dosage form otherthan the therapeutic ingredient. Although they are inert, they may influence the quality of aproduct owing to interaction with the drug substance affecting thephysical properties of the dosage form or influencing theproduction process.

To prevent such effects: Excipients should be examined carefully and critically for compliance withestablished 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 is of crucial importance to the pharmaceuticalindustry, and for this reason numerous checks are made at everystage of production to ensure that quality is not compromised andthat the code of good manufacturing process is adhered to.

Quality control is not only a laboratory procedure, but also theprocedures through which a raw material is transformed to adrug and the finished product till it is used by the patient.

One of the important function of quality control department isto establish specifications for raw materials, packing materials,intermediates and finished products to ensure the quality.

Quality control procedures include:

Sampling of raw materials- All incoming raw materials are initially quarantined andsamples are taken and tested to ensure that the material meetsstrict purity guidelines.- This testing involves both microbiological and chemicaltesting, as is laid out in the relevant pharmacopeia (a referencebook on the preparation of pharmaceuticals three arepublished British, United States and European).

In-process checksThe manufacturing staff carry out checks on such things as tabletweight and size at frequent intervals.At hourly intervals the quality control staff take samples to check forcontamination and to ensure that composition is as expected. Final product checkingChecking similar parameters to those measured during production. Monitoring cleaningWhen a batch of a certain drugs has been made, all equipment thathas been used must be cleaned.When the next pharmaceutical to be made on that line is going to bedifferent, this cleaning must be particularly through to preventcontamination. In this instance, after cleaning the QC staff takeswabs off each piece of equipment and test them to see if they candetect the presence of the active previously used.

The results of all these tests are recorded on the batch records forthe pharmaceutical, as well as the name and batch number of thepharmaceutical made immediately prior on the same productionline. Raw material standardization is the only way for all the drugmanufactures to produce the drugs in same quality and to maintainthe uniformity.Raw materials1. MedicinalMineralsHerbs and animals etc.Microbes, pathological products, healthy tissues, drugs2. Non medicinal (vehicles)Alcohol, lactose, sugar, white petroleum jelly, maize starch,coconut oil, wax

Incoming raw material Transfer Store Sampling

Identification

Analysed

Purity testingManufactureEquipments

Inspected Assessed andcontrol of microbialcontamination

Finishedproducts

Representativesamples analysedDocumented

Quality control can be defined as:Day-to-day control of the quality of Raw materials (active or inactive) Containers & packaging materials Semi finished & finished drug products Also carry out IPC tests during manufacture & assessment of results &making necessary measures.

Adequate and proper documentation (GDP)

Quality assurance can be defined as:Responsibility of an organization to determine that:

Systems & facilities and standard operation procedures (SOPs) ofproduction & analysis are adequate and strictly followed toassure that the drug product will meet the quality specifications.

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

Good raw material specifications must be written in preciseterminology and details of test methods, type of instruments andmanner of sampling must be identified. Table 27-1 lists general tests, limits and other physical or chemical data forraw 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 numbersto all raw materials received and quarantines them untill they areapproved for use.

Each raw material is sampled according to standard samplingprocedures and is sent to the quality control laboratory for testingaccording to the written procedures (Table 27-2). If acceptable, it is moved to the release storage area, after beingproperly stickered to indicate the item number, name of material, lotnumber, date of release, reassay date and signature of the qualityassurance inspector.

It is retested as necessary according to an established scheduleto assure that it still conforms to specifications at time of use. Quality assurance personal should keep preservation samplesof active raw materials that consist of at least twice the necessaryquantity to perform all tests required to determine whether thematerial meets the established specifications. These preservationsamples should be retained for at least 7 years.

Approved materials should be rotated so that the oldest stock is usedfirst. Any raw material not meeting specifications must be isolated fromthe acceptable materials, stickered as a rejection, and returned to thesupplier or disposed of promptly.

Quality control of raw materials In-process controlIntroductionTo 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. The physical, chemical and biological properties that characterize the acceptable quality of the drug are established. 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.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. Quality control is of crucial importance to the pharmaceutical industry, and for this reason numerous checks are made at every stage of production to ensure that quality is not compromised and that the code of good manufacturing process is adhered to.Quality control procedures include: 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. 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.Slide11Quality control can be defined as: Day-to-day control of the quality of Raw materials (active or inactive) Containers & packaging materials Semi finished & finished drug products Also carry out IPC tests during manufacture & assessment of results & making necessary measures. Adequate and proper documentation (GDP) 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. 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. 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.Slide16