Sterile dosage forms

S. Turco and R. E. King, Sterile Dosage Forms, Their Preparation and Clinical Application, Lea and Eebiager, Philadelphia, Pa., 1974. 

Turco S. Young R.E. (19S7) Sterile Dosage Forms, 3rd edn. Easton, Philadelphia Lea and Febiger. United States Pharmacopoeia (1995) 23rd revision. Rockville, MD US Pharmacopoeia Convention. 

S. Turco, Sterile Dosage Forms, 4th ed., Lea Febi-ger, Philadelphia, 1994. 

Turco, S. and King, R.E. (1974). Sterile Dosage Forms. Lea Fehiger, Philadelphia. 

The objective is to provide standard procedure for performing the preservative efficacy test for nonsterile and sterile dosage forms. 

Appearance, assay, and degradation products, preservative, and antioxidant content as applicable should be considered for all dosage forms. The microbial bioburden of sterile dosage forms must be controlled and tested in compliance with pharma-copeial and/or internal specifications. The microbial bioburden of nonsterile dosage forms should be controlled, with appropriate sampling and testing. 

Table 3 Checklist on Process Evaluation Leading to Optimization and Validation of a Liquid Sterile Dosage Form... 

Fig. 9 Flow chart of continuous production line for sterile dosage forms.

Fig. 11 Flow diagram of continuous transfer chamber (with UV radiation) for the production of sterile dosage forms. (From Ref courtesy of ISPE.)...

Turco, S. Sterile Dosage Forms Their Preparation and Clinical Application Lea Febiger Philadelphia, PA, 1994. 

SVIs must be sterile and free from pyrogens and foreign particulate matter. These three major characteristics distinguish sterile dosage forms from any other pharmaceutical product. 

This chapter is a comprehensive review of the excipients included in the injectable products marketed in the United States, Europe, and Japan. A review of the literature indicates that only a few articles that specifically deal with the selection of parenteral excipients have been published. However, excipients included in other sterile dosage forms not administered paren-terally, such as solutions for irrigation, ophthalmic or otic drops, and ointments, will not be covered. 

The sterility of a sterile dosage form can only be guaranteed while it is protected from the surrounding non-sterile environment within a container made from materials impermeable to microbial penetration. 

The extent to which the microbiological controls are required to be applied in the manufacture of non-sterile dosage forms is primarily a function of two factors consequences of infection to the patients and probability of microorganisms proliferating in the product. 

Route of administration Type of non-Aqueous liquids -sterile dosage form Non-aqueous fluids Solid dosage forms... 

All preservative systems for both parenteral and non-sterile dosage forms should meet the 3 log reduction at 14 days for bacteria., i.e., USP category I requirements. EP/BP Antimicrobial Effectiveness Testing would be run only if requested by the Marketing Group. 

Fig. 1 Sterile dosage form processing equipment useful for clinical supply manufacture in the pilot plant. (A) Vial and ampule washer (Metromatic. Oyster Bay, NY). (B) Steam sterilizer (Amsco Finn-Aqua, Apex, NC). (C) Vial filler (TL Systems Corp., Minneapolis). (D)Lyophilizer (Edwards High Vacuum International, Tonawanda, NY). (E) Vial capper (The West Co., Phoenix-ville, PA).

The process equipment should cover a wide range of sizes, rmits, volumes, and operating conditions, e.g., speeds, for maximum flexibility in relationship to batch size and sterile dosage form requirements. Examples of pilot plant equipment utilized for the manufacture of sterile products are shown in Fig. 1. 

Because of FADAMA, the SUPAC process has been extended by the FDA to include sterile dosage forms, analytical methods, product labeling, and product packaging postapproval changes. 

The uses of parenteral products for animals and the development process of these ate nearly identical to those products used for humans. The sterile dosage form types include solutions, suspensions, emulsions, and lyophilized powders. Any dosage form must be chemically, physically, and microbiologically stable, sterile, easy to inject, cause minimal pain and irritation upon injection, and packaged in appropriate vial sizes. Multiple-use vials are more common in animal health to treat herds/flocks). 

Dosage Forms and Product-Contact Components The object of aseptic manufacture is to bring a sterile dosage form and the finished presentation s presterilized product contact components together without contaminating them. Confidence of their sterility is of major importance. This means validated sterilization processes and low levels of microbiological contamination prior to their sterilization. 

Filtered sterile dosage forms may be collected in sealed vessels in the aseptic filling room for subsequent connection to the filling machine, or the filler outlet may be connected directly to the filling machine. 

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