Preliminary Evaluation of Stability Data for Dolutegravir-Containing Triple Active Formulations Intended for PEPFAR. Degradation of Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide as the Limiting Factor.

FDA reviews applications that are filed under the PEPFAR program to ensure that these products are manufactured to FDA's stringent requirements. Dolutegravir is a comparatively recent molecular entity that represents an advance over previous products. The stability behaviors of tablets that contain dolutegravir, lamivudine, and tenofovir disoproxil fumarate and tablets that contain dolutegravir, emtricitabine and tenofovir alafenamide were surveyed and it was found that tenofovir-related degradants increase the most and are the parameters most likely to result in product failure. A desiccant is advantageous and this desiccant should remain in the bottle after it has been opened. In-use studies simulate consumer use. Bottles are stored at 30 °C/75% RH and opened for about 1 min a day. Water content increased significantly and the rate of degradation was faster than the degradation rate observed during long-term storage. The data predict that most formulations containing TDF will stay within specification over 4 years of long-term storage followed by dispensing one tablet per day. With the current data it appears that some TAF-containing formulations may fail under similar conditions. However, the data are limited and preliminary and it is possible that the situation may improve as more stability data are acquired.

Safe use of hazardous chemicals.

This unit provides protocols for some commonly used disposal and decontamination procedures along with analytical techniques that are used to verify that reagents have been decontaminated. Some of the specific reagents covered are diaminobenzidine, ethidium bromide, cyanogen bromide, and chloromethylsilane. With modification, these assays may also be used to determine the concentration of a particular chemical.

Biosafety: guidelines for working with pathogenic and infectious microorganisms.

This unit, in conjunction with local and national guidelines and regulations (see APPENDIX 1B), provides the basic biosafety information needed to perform the procedures detailed in this manual. Topics discussed include routine precautions when working with biohazards, disinfectants, disposal of biohazards, biosafety levels (as established by the U.S. National Institutes of Health and the U.S. Centers for Disease Control and Prevention), animal facilities, and clinical laboratories. In addition, resources for more information are provided in the Literature Cited and Key References sections and in URLs given within the text, as well as the Internet Resources section.

Laboratory safety.

The pursuit of scientific knowledge has been considerably advanced by the use of a wide variety of hazardous substances, including radioisotopes, hazardous chemicals, and biohazards. This appendix addresses each of these classes of hazards and primary safety precautions that need to be considered.

Safe use of hazardous chemicals.

This appendix provides protocols for some commonly used disposal and decontamination procedures along with analytical techniques that are used to verify that reagents have been decontaminated. Some of the specific reagents covered are diaminobenzidine, ethidium bromide, cyanogen bromide and chloromethylsilane. With modification, these assays may also be used to determine the concentration of a particular chemical.

Safe use of hazardous chemicals.

This appendix provides protocols for some commonly used disposal and decontamination procedures along with analytical techniques that are used to verify that reagents have been decontaminated. Some of the specific reagents covered are diaminobenzidine, ethidium bromide, cyanogen bromide and chloromethylsilane. With modification, these assays may also be used to determine the concentration of a particular chemical. Precautions are also detailed for routine handling of viable pathogenic microorganisms, as well as all human-derived materials, because they may harbor dangerous pathogens such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and a host of bacterial pathogens.

Biosafety: guidelines for working with pathogenic and infectious microorganisms.

This unit, in conjunction with local and national guidelines and regulations, provides the basic biosafety information needed to perform the procedures detailed in this manual. Topics discussed include routine precautions when working with biohazards, disinfectants, disposal of biohazards, biosafety levels (as established by the U.S. National Institutes of Health, and the Centers for Disease Control and Prevention), animal facilities, and clinical laboratories. In addition, resources for more information are provided in the Literature Cited and Key References sections and in URLs given text and within the Internet Resources section.

Biosafety: guidelines for working with pathogenic and infectious microorganisms.

This unit, in conjunction with local and national guidelines and regulations, provides the basic biosafety information needed to perform the procedures detailed in this manual. Topics discussed include routine precautions when working with biohazards, disinfectants, disposal of biohazards, biosafety levels (as established by the U.S. National Institutes of Health, and the Centers for Disease Control and Prevention), animal facilities, and clinical laboratories. In addition, resources for more information are provided in the Literature Cited and Key References sections and in URLs given text and within the Internet Resources section.

Safe use of hazardous chemicals.

This appendix presents useful basic information, including common abbreviations, useful measurements and data, characteristics of amino acids and nucleic acids, information on radioactivity and the safe use of radioisotopes and other hazardous chemicals, conversions for centrifuges and rotors, characteristics of common detergents, and common conversion factors.

Laboratory safety.

This appendix provides protocols for some commonly used disposal and decontamination procedures along with analytical techniques that are used to verify that reagents have been decontaminated. Some of the specific reagents covered are diaminobenzidine, ethidium bromide, cyanogen bromide and chloromethylsilane. With modification, these assays may also be used to determine the concentration of a particular chemical. Precautions are also detailed for routine handling of viable pathogenic microorganisms, as well as all human-derived materials, because they may harbor dangerous pathogens such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and a host of bacterial pathogens.