Administration products

This chapter should be sufficient to guide the engineer or manager through the initial stages of introducing a sound and effective planned maintenance system. However, as in any establishment - production, administration or (as in this case) engineering - without the commitment and... 

Toxicity was evaluated in mice, rats, dogs and monkeys following both acute and chronic product administration at various dosage levels (1-200 mg kg-1 range), with a proportion of animals displaying hypersensitivity/anaphylactic-like responses at high dosage levels. 

The major clinical study underpinning product approval was a randomized, double blind study in which 71 CTCL patients were administered the product at one of two dosage levels (9 or 18 [tg kg 1 day ) overall, 30 per cent of patients experienced an objective tumour response. Serious side effects potentially associated with product administration include acute hypersensitivity-type reactions, vascular leak syndrome and visual impairment. Additional adverse reactions include flu-like symptoms, headache, hyper- or hypo-tension, as well as digestive upset. Ontak is manufactured by Seragen Inc. and is distributed by Ligand Pharmaceuticals. 

Pre-approval safety and efficacy clinical studies involved product administration to 2500 adults with either type-1 or -2 diabetes. The primary efficacy parameter measured was glycaemic control (as measured by the reduction from baseline in haemoglobin Ale). Hypoglycaemia was the most commonly reported adverse effect. Trials also showed a greater decline in pulmonary function in the Exubera group, and product should not be administered to patients with underlying lung disease, or to smokers. Exubera was developed by Nektar Inc. and is marketed under licence by Pfizer. 

Persons expressing 5 per cent or above of the normal complex levels experience less severe clinical symptoms. Treatment normally entails administration of factor VIII complex purified from donated blood. More recently, recombinant forms of the product have also become available. Therapeutic regimens can require product administration on a weekly basis, for life. About 1 in 10 000 males are born with a defect in the factor VIII complex and there are approximately 25 000 haemophiliacs currently resident in the USA. 

Owing to the frequency of product administration, the purification procedure for recombinant factor VIII C must be particularly stringent. Unlike the situation pertaining when the product is purified from human blood, any contaminant present in the final product will be non-human and, hence, immunogenic. Sources of such contaminants would include ... 

When compared with human monoclonals (half-life 14-21 days), murine monoclonals administered to humans display a relatively short half-life (30-40 h). Chimaerization increased serum half-life by fivefold, with typical values of 230 h being recorded (Table 13.4). A prolonged half-life is desirable if the antibody is to be used therapeutically, as it decreases the required frequency of product administration. Chimaeric antibodies also allow activation of Fc-mediated functions (e.g. activation of complement, etc.), as this domain displays human sequence. 

Rosenblat M., Volkova N., Coleman R., and Aviram M., Pomegranate by-product administration to apolipoprotein E-deficient mice attenuates atherosclerosis development as a result of decreased macrophage oxidative stress and reduced cellular uptake of oxidized low-density lipoprotein, J. Agric. Food. Chem., 54, 1928, 2006. 

Another factor that may enter into the selection paradigm for the most appropriate species for evaluation of a specific gene therapy product is the route/method of product administration. For example, if the delivery of the... 

In the developmental process for many drugs, the drug product is administered under controlled conditions to healthy, normal individuals or to the targeted patient population. This is done to characterize the rate and extent of absorption, the bioavailability, of the active drug contained in the product. The bioavailability is estimated from the measured concentrations of the drug that appear in serial blood specimens collected over a period of time after product administration. Basic statistical principles govern the behavior of the typical bioanalytical procedure used to measure these concentrations in the collected blood specimens. 

Anaphylactic reactions have also been reported following the consumption of foods derived from, or containing, soy beans. Recently there has been concern at the concentration of phytoestrogens in some soy-derived products. Administration of soy protein to humans has resulted in significantly decreased serum lipid concentrations. " ... 

The organization, as it finally shaped up, was headed by the Defense Production Administration (later Office of Defense Mobilization) which established policy and coordinated the activities of various operating units. Except for the Office of Price Stabilization, most mobilization agencies were set up within existing government agencies. 

National Production Authority, Defense Production Record, weekly. May 3, 1951-Jan. 1, 1953. Summarizes activities of Defense Production Administration and related federal agencies. Includes certificates of necessity issued by D.P.A. for rapid amortization of new chemical facilities. 

Another consideration in the patient with injuries or surgery is the potential need for blood product administration (Table 24-5) to... 

Other issues that must be considered with blood product administration include monitoring for transfusion-related reactions and attention to appropriate warming, particularly when large volumes are given to pediatric patients, because hypothermia is associated with increased fluid requirements and mortality." ... 

Source documents are composed of hospital records, office charts, laboratory data sheets, subject diaries, pharmacy dispensing records, recorded data from automated instruments, x-rays, etc. Source documents should be legible and should document that the subject is participating in a clinical trial. Some of the key areas to cross reference source documents to case report forms and regulatory criteria are the informed consent process, inclusion/exclusion criteria, adverse experiences, investigational product administration, concomitant medications administered to the subject during the trial, withdrawal from the study for any reason, and subjects lost to follow-up. 

To establish the "quality" of the human body, it is necessary to have correct information concerning its environment, and the food and pharmaceutical products administrated within less than 24 hours. With this knowledge, the medical practitioner will be able to request and establish the best correlation between analytical results and illness also, the analyst can select the best method, free of interferences. The sample collection is of major importance in this case, especially when an immunological method is applied. It is well known that the human body is able to synthesize antibodies during the same period of time as sample pickup. It is possible for these antibodies to act as interfering species in analysis and to increase the uncertainty. As a result, an increased value of uncertainty may be recorded when a tourniquet is put on different places around the arm for blood sample collection. It is also important to know the exact time of day a sample has been taken. 

From a practical standpoint this necessitated product administration by continuous infusion over a 90-min period. Do-main-deleted engineered variants (trade names Ecokinase and Retavase), however, display half-lives in the region of 15-20 min, facilitating product administration by a single i.v. injection. 

There are however additional activities (e.g. warehousing, distribution) whereby information is built up in order to establish the total stability/safety of the product, the clinical efficacy of the product/device and the functional acceptance of the product/ pack/device in the hands of the ultimate user. (This is particularly relevant where the pack assists product administration see Appendix 8.9 for further details.)... 

Appendix 8.9, in identifying how packs are becoming increasingly complex and sophisticated (e.g. to assist in product administration or as special devices), indicates the various types of additional testing which are now essential to approval. Appendix 8.10 lists support papers written by the author with reference to plastics. 

Closure systems are becoming more complex and sophisticated, incorporating features related to such aspects as tamper-evidence, tamper-resistance, child-resistance, special easy opening closures for the elderly, and product administration. 

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