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Biomedical subjects

J Geigert

Publications and source records attributed to J Geigert.

At least 19 recordsLinked to original sources
PubMed1997

Appropriate specifications at the IND stage.

Biopharmaceutical product specifications are to be "scientifically sound and appropriate". However, how does a biopharmaceutical company determine what are acceptable specifications for its product at the early stages of clinical development? Are there really enough test data at the start of the IND trials to "establish" specifications? As an industry, are we doing too many tests at the IND stage (i.e. following the "must do every test on someone's published list" syndrome), and then finding that specifications need to be set for each test we run? Are we feeling pressurised (either by regulatory agencies or by our own corporate cultures) to set unrealistic and tight specifications at the IND stage, and then later regretting how to justify loosening them when we gain more experience with the release testing or stability of our products? A discussion on how to set practical product specifications for biopharmaceutical products at the IND stage is presented.

Biopharmaceutics↗
PubMed1988

The long-term stability of recombinant (serine-17) human interferon-beta.

Escherichia coli-derived (Serine 17) human interferon-beta (HuIFN-beta SER) was formulated with SDS and placed at multiple isothermal temperatures (-70 degrees C to 37 degrees C). Three stability-indicating test methods (bioassay, SDS-PAGE, RP-HPLC) were used to evaluate the long-term stability of this preparation. No change was observed when stored for nearly a year at either -70 degrees C or 4 degrees C. At the elevated temperatures, proteolytic cleavage, noncovalent oligomer formation, and loss of antiviral activity were observed. The absence of a carrier protein makes this stable IFN-beta frozen reference preparation useful as a standard in both biological assays and protein chemical methods of analysis.

Biological Assay↗
PubMed1988

Parameters for the evaluation of long-term stability of tumour necrosis factor preparations.

Escherichia coli-derived Tumour Necrosis Factor (TNF) was formulated in the absence of a protein-carrier, both as a solution and as a lyophilized preparation. By means of three stability-indicating test methods (bioassay, SDS-PAGE, IEF), the long-term stability of these TNF preparations was evaluated. Both preparations showed no change upon storage for 9 months at -70 degrees C and -20 degrees C. Depending upon the test method, different rates of change were detected at elevated temperature. The analysis presented will assist in the design of future TNF reference standards.

Amino Acid Sequence↗
PubMed1987

Isolation and characterization of a novel nonheme chloroperoxidase.

Chloroperoxidase, purified from the fermentation of Curvularia inaequalis, had a molecular weight of approximately 240,000 and was composed of 4 subunits of identical molecular weight (Mr 66,000). The enzyme was specific for I-, Br- and Cl-, and inactive toward F-. The optimum pH of the enzyme was centered around 5.0. X-ray fluorescence revealed that the enzyme contained 2.2 atoms of zinc and 0.7 atom of Fe per molecule of protein. The enzyme had no heme-like compound as a prosthetic group, making it the first nonheme chloroperoxidase to be reported. Under oxidative conditions that rapidly inactivated other haloperoxidases, this enzyme was remarkably stable.

Chloride Peroxidase↗
PubMed1987

Potency stability of recombinant (Serine-17) human interferon-beta.

The antiviral activity of Escherichia coli-derived (Serine-17) human interferon-beta, formulated with human serum albumin, is stable for 2 years when lyophilized and stored under refrigeration. This product shows an Arrhenius line fit for the stability of its activity when tested at multiple isothermal temperatures (25-80 degrees C). In both isothermal and nonisothermal elevated temperature studies, increasing the level of human serum albumin in the formulation results in increased thermal stability.

Cell Line↗
PubMed1986

Epoxidation of alkenes by chloroperoxidase catalysis.

Chloroperoxidase from Caldariomyces fumago catalyzes the peroxidation of alkenes to epoxides. This enzyme is the only haloperoxidase of four tested capable of carrying out the reaction. These results further establish chloroperoxidase as a unique haloperoxidase, and adds this enzyme to the short list of other enzymes (e.g., cytochrome P-450) known to epoxidize alkenes.

Alkenes↗
PubMed1983

DMSO is a substrate for chloroperoxidase.

Dimethyl sulfoxide has been used as a nonaqueous organic solvent in haloperoxidase reactions. However, it has been found that this solvent is not inert under chloroperoxidase reaction conditions, forming the halosulfoxide, the sulfone, and the halosulfone. The biological significance of this finding is briefly discussed.

Chloride Peroxidase↗
PubMed1983

Peroxide oxidation of primary alcohols to aldehydes by chloroperoxidase catalysis.

Chloroperoxidase catalyzes the peroxidation of primary alcohols, specifically those that are allylic, propargylic, or benzylic. Aldehydes are the products. The reaction displays appreciable activity throughout the entire pH range investigated, namely pH 3.0-7.0. This enzyme is the only haloperoxidase of four tested capable of carrying out the reaction. These results further establish chloroperoxidase as a unique haloperoxidase.

Alcohols↗
PubMed1983

Novel haloperoxidase substrates. Alkynes and cyclopropanes.

Two new substrate classes that can be halogenated by haloperoxidase have been discovered. The enzymatic halogenation of alkynes yields alpha-halogenated ketones, and the enzymatic halogenation of cyclopropanes yields alpha, gamma-halohydrins. The general reaction scheme proposed involves the initial formation of hypohalous acid as the key intermediate. This proposed mechanism, based upon observed differences in product selectivities, is opposite of that proposed previously, based upon observed differences in substrate selectivities. The biosynthetic implications of these novel haloperoxidase reactions are also discussed.

Alkynes↗
PubMed1983

Neighboring group migration in enzyme-mediated halohydrin formation.

Enzymatic halogenation of the double bond in allyl halides was influenced by intramolecular participation of the allylic halogen in the substrate molecule. Migration of the allylic halogen to the central carbon atom was observed in the enzymatic chlorination of allyl bromide, but not in the enzymatic bromination of allyl chloride. These results parallel the neighboring group effects observed for non-enzymatic halogenation of allyl halides.

Allyl Compounds↗
PubMed1983

Haloperoxidases: Enzymatic Synthesis of alpha,beta-Halohydrins from Gaseous Alkenes.

The enzymatic synthesis of alpha,beta-halohydrins from gaseous alkenes is described. The enzymatic reaction required an alkene, a halide ion, dilute hydrogen peroxide, and a haloperoxidase enzyme. A wide range of gaseous alkenes were suitable for this reaction, including those containing isolated, conjugated, and cumulative carbon-carbon double bonds. Chlorohydrins, bromohydrins, and iodohydrins could be formed. The combining of this enzymatic synthesis with a previously described enzymatic synthesis of epoxides from alpha,beta-halohydrins provides an alternate pathway, other than the well-known enzymatic direct epoxidation pathway, from alkene to an epoxide.

Journal Article↗
PubMed1983

Novel haloperoxidase reaction: synthesis of dihalogenated products.

The enzymatic synthesis of vicinal, dihalogenated products from alkenes and alkynes is described. The enzymatic reaction required an alkene or alkyne, dilute hydrogen peroxide, a haloperoxidase, and molar amounts of halide ions. Vicinal dichloro, dibromo, and diiodo products could be formed. A hydroxyl group on the carbon adjacent to the carbon-carbon double or triple bond lowered the halide ion concentration needed to produce the dihalo product. This reaction offers one explanation for the origin of natural, vicinal, dihalogenated products, such as those found frequently in marine microogranisms.

Journal Article↗
PubMedDate not supplied

Overview of the stability and handling of recombinant protein drugs.

Recombinant protein products have now been added to the inventory of parenteral drugs, and because of their newness, there exists a certain mystique about how they need to be handled. This article describes how the manufacturer determines both the shelf life and the proper preparation procedures for administering these new drugs. It will be shown that some recombinant protein drugs have comparable shelf lives to other parenteral drugs on the market. Also, it will be shown that, as for any parenteral drug, the manufacturer's recommended procedure for handling and administration of a recombinant protein drug should be followed.

Drug Industry↗