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For multiproduct cleaning validation, the conventional approach for setting an acceptance limit for the process residue is based on the maximum allowable carryover (MAC) of the active pharmaceutical ingredient (API) (depending on the process soil, API refers to the active pharmaceutical ingredient in the drug product, drug substance, or drug substance intermediate). However, if the API becomes pharmacologically inactive during cleaning the acceptance limit does not need to be based on active product. This is an important consideration in biopharmaceutical manufacturing because the cleaning conditions are generally aggressive enough to inactivate the product. The experimental approach and analytical methods for assessing inactivation of the API during cleaning are described in Part I. A rational approach for setting safety-based acceptance limits for inactivated product and process residuals is described in Part II. The scope of this paper is limited to biopharmaceutical cleaning processes; nonetheless, the underlying concepts may be useful in designing inactivation studies and setting acceptance limits for other types of pharmaceutical cleaning processes. [ABSTRACT FROM AUTHOR]

Biopharmaceutical cleaning and sterilization cycles are designed to expose product contact equipment to pH and temperature extremes. Under these conditions biological products tend to become pharmacologically inactive. This paper describes a methodology for assessing inactivation during cleaning and setting acceptance limits based on inactive product. The scope of this paper is limited to process residues of biological products; nonetheless, the underlying principles may be useful in setting limits for other types of inactive products. [ABSTRACT FROM AUTHOR]

Primary care physicians often prescribe contraceptives to women of reproductive age with comorbidities. Novel delivery systems (e.g., contraceptive patch, contraceptive ring, single-rod implantable device) may change traditional risk and benefit profiles in women with comorbidities. Effective contraceptive counseling requires an understanding of a woman's preferences and medical history, as well as the risks, benefits, adverse effects, and contraindications of each method. Non-contraceptive benefits of combined hormonal contraceptives, such as oral contraceptive pills, include regulated menses, decreased dysmenorrhea, and diminished premenstrual dysphoric disorder. Oral contraceptive pills may be used safely in women with a range of medical conditions, including well-controlled hypertension, uncomplicated diabetes mellitus, depression, and uncomplicated valvular heart disease. However, women older than 35 years who smoke should avoid oral contraceptive pills. Contraceptives containing estrogen, which can increase thrombotic risk, should be avoided in women with a history of venous thromboembolism, stroke, cardiovascular disease, or peripheral vascular disease. Progestin-only contraceptives are recommended for women with contraindications to estrogen. Depo-Provera, a long-acting injectable contraceptive, may be preferred in women with sickle cell disease because it reduces the frequency of painful crises. Because of the interaction between antiepileptics and oral contraceptive pills, Depo-Provera may also be considered in women with epilepsy. Implanon, the single-rod implantable contraceptive device, may reduce symptoms of dysmenorrhea. Mirena, the levonorgestrel-containing intrauterine contraceptive system, is an option for women with menorrhagia, endometriosis, or chronic pelvic pain. [ABSTRACT FROM AUTHOR]