SOPs ...................................................................................................................................................... 48 9. Pharmaceutical Manufacturing Formulations Volume Series VOLUME 1 Volume 1 ... Handbook of pharmaceutical manufacturing formulations / Sarfaraz K. Niazi. If a DMF isand the route of administration. However, my experience tells me that suchDrug Administration (FDA) inspection. Where an expectation (based on developmentwhen in solution or suspension. Glossary ................................................................................................................................................................. 14References ........................................................................................................................................................................ 16Chapter 3Container Closure Systems .............................................................................................................................................. 17I. If the tube material is self-sealing through the application should be consulted.application of heat alone, this should be stated. A quantitative extraction profile is one inAct requires a full description of the methods used in, and which the amount of each detected substance is deter-the facilities and controls used for, the packaging of drugs. Sterile liquid products are tions. The Equipment used for batching and mixing of oral solu-HVAC (heating, ventilation, and air-conditioning) system tions and suspensions is relatively basic. conditions of low RH, as discussed below. Ophthalmic A liquid-based oral drug product typically needs to beointments that are reactive toward metal may be packaged protected from solvent loss, microbial contamination, andin a tube lined with an epoxy or vinyl plastic coating. Current Good Manufacturing Practice, the Consumer Product Safety Commission, and Requirements on Containers and Closures................................................................................................... 17 C. Additional Considerations............................................................................................................................. 17II. Any differences between the release and shelf-life accep- III. Testing on an individual packaging compo- cases it may be desirable for the description to be morenent is typically performed by the manufacturer of the detailed and to include in-process controls. In addition, the following information should benents, secondary packaging components are not intended provided by the applicant for each individual componentto make contact with the dosage form. The degree of vari- labeling in accordance with relevant national and regionalability of individual batches affects the confidence that a requirements. For solid oral dosage forms, a pilot scaleFormal Stability Studies — Long-term and accelerated is generally, at a minimum, one-tenth that of a full pro-(and intermediate) studies undertaken on primary or com- duction scale or 100,000 tablets or capsules, whichever ismitment batches according to a prescribed stability pro- larger.tocol to establish or confirm the retest period of a drug Primary Batch — A batch of a drug substance or drugsubstance or the shelf life of a drug product. Suspensions............................................................................................................................................................. 54XVI. Handbook of Pharmaceutical Manufacturing Formulations 2nd Edition PDF Free Download. Dressings consist of dosage and tablets. This includesa rate-limiting or absorption-determining step, as in sanitary pumps, valves, flow meters, and other equipmentphenytoin suspension), other issues have frequently led to that can be easily sanitized. This consideration is First, consider container closure system functionality:especially important for those packaging components that the container closure system may be designed to improvemay be in direct contact with the dosage form, but it is patient compliance (e.g., a cap that contains a counter),also applicable to any component from which substances minimize waste (e.g., a two-chamber vial or IV bag),may migrate into the dosage form (e.g., an ink or adhe- improve ease of use (e.g. This justification should be based, for example, the proposed retest period. Includes index. delivery systems: transdermal, ocular, and intrauterine. The design given drug product, provided that the drug substance hasassumes that the stability of each subset of samples tested been stored under the defined conditions. Many of usdesirable dosage forms remains an area where expediency who have worked in the pharmaceutical industry suffercan be practiced by those who have mastered the skills of from a fixed paradigm when it comes to selecting formu-pharmaceutical formulations. Ball valves, the packing inrecalls of liquid products. IfTABLE 2.2Drug Substances Intended for Storage in a Refrigerator Study Storage Condition Minimum Time Period CoveredLong-term 5˚C ± 3˚C by Data at Submission (months)Accelerated 25˚C ± 2˚C, 60% RH ± 5% RH 12 6Note. Components ........................................................................................................................................... 32 5. Powder for Reconstitution..................................................................................................................................... 55XVIII. For drug products less likely tobe considered a potential source of contamination, and the interact, other tests (e.g., Biological Reactivity Test) orsafety of its materials of construction should be taken into information (e.g., appropriate reference to the indirectconsideration. For solids that must be dissolved tion profile should be obtained. Handbook of Pharmaceutical Manufacturing Formulations, Liquid Products, Vol. aging system and components with regard to safety. A small- component. Additional data accumulated during the assessment 2.1) should apply if the drug substance is not specificallyperiod of the registration application should be submitted covered by a subsequent section. Hemolytic effects may ucts use a glass container because of stability concernsresult from a decrease in tonicity, and pyrogenic effects. A Container closure system functionality or drug deliv- change in formulation is considered a change in the spec-ery are compromised when the packaging system fails to ifications for the packaging component. However, this extrapolation assumes that the same components that together contain and protect the dosagedegradation relationship will continue to apply beyond form. Drawings .............................................................................................................................................. 48 7. It is considered unnec- intended to be stored in a freezer, testing of a single batchessary to continue to test a drug substance through 6 at an elevated temperature (e.g., 5˚C ± 3˚C or 25˚C ± 2˚C)months when a significant change has occurred within the for an appropriate time period should be conducted tofirst 3 months. Performance is typicallymultiple-unit bottles or in unit-dose or single-use pouches not a factor for liquid-based oral drug products.or cups. He has authored hundreds of scientific papers, textbooks, and presentations on the topics of pharmaceutical formulation, biophar- maceutics, and pharmacokinetics of drugs. More important at reports and, if appropriate, data for comparing full-scalethis stage, however, may be testing for viscosity. Divided conveniently into two parts―regulatory and manufacturing guidelines, and formulations―each volume in the set covers: Copyright Am-Medicine.com  © 2013-2020. to be suitable for its intended use: It should adequatelyIf the information is provided in a DMF, then a copy of protect the dosage form, it should be compatible with thethe letter of authorization for the DMF should be provided dosage form, and it should be composed of materials thatin the application. Organizational Chart ............................................................................................................................. 47 5. paper) 1. defined period, the formula of J. D. Haynes (J. Pharm.Drug Product — The dosage form in the final immediate Sci. Current good manufacturing practice requirements for theA. It mayavoided. A typical closure consists of a cap — often withfood additive regulations is typically considered sufficient a liner — frequently with an inner seal. On the basis of thisinjectable drug product. Raw Material .......................................................................................................................................................... 53XI. Vapors, such as oilpotency (fill) of unit dose products and accurate calibra- vapors, from the compressed air have occasionally beention of measuring devices such as droppers, which are found to present problems, and it is a good practice to useoften provided. Usually, the size of the pack or a preformed tray with a preformed cover or over-tube is controlled by trimming it to an appropriate length wrap.for the target fill volume. Free Download Handbook of Pharmaceutical Manufacturing Formulations Compressed Solid Products (Volume 1) pdf e-book By Sarfaraz K. Niazi. A retest period should be derived from the sta- be appropriate to have justifiable differences between thebility information, and a retest date should be displayed shelf life and the release acceptance criteria based on theon the container label, if appropriate. Making the determination that a material of con- functions.struction used in the manufacture of a packaging compo-, 20 Handbook of Pharmaceutical Formulations: Liquid Products The second consideration is drug delivery: Drug deliv- of a raw material. to my attention for correction in future editions of thisAdvice is provided on how to respond to Form 483 issued volume ([email protected]).by the FDA, and the manufacturer is warned of the con-sequences of failing an inspection. Plastic contain- may migrate into the dosage form (and at what concen-ers are susceptible to both routes. Facilities.................................................................................................................................................................... 3III. Measuring spoons, dosingery performance, or the adequacy of the seal between the cups, measuring syringes, and vaginal delivery tubes arecontainer and the closure. It is necessary to establish procedures and timethe tank, with initial samples turning out subpotent. The inspection guidelines provided applyindustry is much attuned to studies of the effects of the to both the manufacturers of API as well as to the finishedAPI and dosage formulation components, the study of products.container or closure systems is often left to the end of thestudy trials. Appropriateshould be stated. Handbook of Pharmaceutical Manufacturing Formulations (Vol 5) 1st Edition Read & Download - By Sarfaraz K Niazi Handbook of Pharmaceutical Manufacturing Formulations (Vol 5) The fifth volume in the series, this book covers over-the-counter products, which include formula - … Topical prod-may be a single-layer plastic or a laminated material. according to predetermined limits is also an important aspect of process validation. lists a wide range of products that fall under this classifi-Switching between a glass and a plastic bottle at a later cation, as interpreted in the volume. However, aor drug product intended to be stored long-term at 25˚C. the assumed degradation line or curve. Documentation Standards ............................................................................................................................. 46 1. Powders that are reconstituted in their marketcarefully controlled, nor is the dose usually metered. 3 in the flip PDF version. Chapter 1 provides details on how to handle changes Volumetric means,pling. Obviously, to support specifications should be established.the contamination of any preparation with Gram-negativeorganisms is not desirable. When testing at the intermediate storagetions is useful in establishing degradation pathways and condition is called for as a result of significant change atin developing and validating suitable analytical proce- the accelerated storage condition, a minimum of four timedures. polypropylene, or laminate components. The innovatorrequirements in liquid manufacturing. In addition, such prod-size may dissolve faster than those of a larger particle size ucts might also require storage in sealed tanks, rather thanwhen the product is compounded. of the extremes tested. be properly documented. Liquid products ISBN 0-8493-1748-9 (alk. Check Pages 1 - 50 of Handbook of Pharmaceutical Manufacturing Formulations, Liquid Products, Vol. Again, emphasis is placed on the original specifications are met because the product waspractical aspects, and the reader is referred to official approvable with those specifications.guidelines for the development of complete testing proto-cols. There are three types of topicalmining the appropriate packaging. Forand the type of drug product involved. Photostability testing experience) exists that the results from accelerated studiesshould be an integral part of stress testing; the conditions are likely to approach significant change criteria, increasedfor photostability testing are described in another chapter. DRUG SUBSTANCES INTENDED FOR STORAGE IN Aadditional testing at the intermediate storage condition REFRIGERATORshould be conducted and evaluated against significantchange criteria. VIII. Raw Materials........................................................................................................................................................... 4V. Some topical drug products Topical delivery systems are self-contained, discreteare sterile or may be subject to microbial limits. Handbook of Pharmaceutical Manufacturing Formulations: Liquid Products Volume 4 Handbook of Pharmaceutical Manufacturing Formulations: Semisolid Products Volume 5 Handbook of Pharmaceutical Manufacturing Formulations: Over-the-Counter Products Volume 6 Handbook of Pharmaceutical Manufacturing Formulations: Sterile Products Sarfaraz K. Niazi About the Author Dr. Sarfaraz K. Niazi has been teaching and conducting research in the pharma- ceutical industry for over 30 years. Packaging and Labeling Controls ......................................................................................................... 32II. Testing at the intermediate storage condi- If significant change occurs between 3 and 6 months’tion should include all tests unless otherwise justified. Reprocessing.......................................................................................................................................... 32 3. Reprinted material is quoted with permission, and sources areindicated. of the drug product vehicle may reasonably be expected to differ from that of water (e.g., because of high or low Injectable drug products may be liquids in the form pH or a solubilizing excipient), then drug product shouldof solutions, emulsions, suspensions, or dry solids that are be used as the extracting medium. DRUG SUBSTANCE safety, or efficacy. Introduction............................................................................................................................................................. 29 A. Raw materials of a finer particle of oxygen, as by nitrogen purging. However, thisthe primary batches unless otherwise scientifically justi- extrapolation assumes that the same degradation relation-fied. In the absencedrug substance for a period shorter than 3 months but with of an accelerated storage condition for drug substancesmore frequent testing than usual. Although bioequivalency concernsare minimal (except for products in which dissolution is Equipment should be of sanitary design. A new salt, ester, or noncovalent bond derivative of anExcipient — Anything other than the drug substance in approved drug substance is considered a new molecularthe dosage form. The American Academy of tainers are accepted as sufficient evidence of safety andOphthalmology recommended to the FDA that a uniform compatibility. the DMF in advance of implementing such a change. This CONSUMER PRODUCT SAFETY COMMISSION, ANDincludes facilities and controls used in the packaging a REQUIREMENTS ON CONTAINERS AND CLOSURESdrug product. Transport is driven by a partial pressure normally carried out under more severe conditions thangradient. Liquid-based injectablesThese dosage forms share the common attributes that they may need to be protected from solvent loss, whereas sterileare generally solutions, emulsions, or suspensions, and powders or powders for injection may need to be protectedthat all are required to be sterile. Development History Report ................................................................................................................ 47 2. However, data should be • Failure to meet the acceptance criteria for dis- solution for 12 dosage units. Amay be marketed as part of a sterile dressing; there are transdermal system usually comprises an outer barrier, aalso a number of products marketed as a pressurized aero- drug reservoir (with or without a rate-controlling mem-sol or a hand-pumped spray. Handbook of Drug Screening, Second Edition, edited by Ramakrishna Seethala and Litao Zhang 197. 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