Sterile parenteral product ophthalmic products

Specific details of the sterility testing of parenteral products, ophthalmic and other non-injectable preparations, catgut, surgical dressings and dusting powders will be found in the British and European pharmacopoeias. 

No discussion of maintenance of sterility is complete without addressing multiple-dose ophthalmic presentations. The normal circumstances for sterile parenteral products are that they are unit dose or, if multiple dose, they are penetrated only by sterile transfer devices (syringes, giving sets, etc.) and used on one patient only. This is not the case for ophthalmic ointments and drops unit-dose presentations are quite unusual and generally used only in hospital practice, for example, after eye surgery. 

Although it is conceivable that there are occasions when almost any pharmaceutical product may be required to be sterile, there are only two broad groups of sterile pharmaceutical products, parenteral products and ophthalmic products. 

Sterile Epinephrine Ophthalmic Solution USP takes us out of the realm of sterile parenteral products into ophthalmics. The manner of presentation of ophthalmics (i.e., as drops or ointments) is likely to be quite familiar. For the most part (but not exclusively) they are in multidose presentations. As such, most formulations include some form of preservative to control proliferation of any microorganisms that may by chance contaminate the product on one or other of the occasions when it is open, or during the time when it is left standing on the bathroom shelf. The inclusion of preservatives in a multidose formulation of an ophthalmic (or parenteral) is not a primary part of the process of achieving sterility. It has quite a separate purpose. 

In contrast, parenteral suspensions have relatively low solids contents, usually between 0.5 and 5%, with the exception of insoluble forms of penicillin in which concentrations of the antibiotic may exceed 30%. These sterile preparations are designed for intramuscular, intradermal, intralesional, intraarticular, or subcutaneous injection. Syringeability is an important factor to be taken into consideration with injectable dosage forms. The viscosity of a parenteral suspension should be sufficiently low to facilitate injection. Common suspending vehicles include preserved isotonic saline solution or a parenterally acceptable vegetable oil. Ophthalmic and optic suspensions that are instilled into the eye/ear must also be prepared in a sterile manner. The vehicles are essentially isotonic and aqueous in composition. The reader should refer to Chapter 12 for further discussion on parenteral products. 

Category I la. Injections, other parenterals including emulsions, otic, sterile nasal products, and ophthalmic products made with aqueous bases or vehicles... 

Sterility is defined as the total absence of all viable life forms. Parenteral products and ophthalmic products are expected to be sterile. Parenteral products must be sterile because their route of administration overrides the body s external physical barriers to infection. Ophthalmic products must be sterile because eye damage is often irreparable. No distinction can be made between microorganisms that are known to be specific causative agents of disease and those that are not. 

Such sterilization procedures (see also Chapter 20) may include heat treatment, filtration, irradiation, recrystallization from a bactericidal solvent such as an alcohol, or for dry products where compatible, ethylene oxide gas. If the raw material is only a minor constituent and the final product is adequately preserved either by lack of Aw, chemically or by virtue of its pH, sugar or alcohol content, an in-process sterilization stage may not be necessary. If, however, the product is intended for parenteral or ophthalmic use a sterilization stage is essential. 

The objectives of the process design and optimisation stages of product development have been discussed in chapter 8, Product Optimisation . For ophthalmic products, like parenterals, process development can be quite challenging because the formulation must be manufactured sterile. Quite often, it is discovered that some formulations cannot withstand a stressful sterile process such as autoclaving. Chemical degradation or changes to the formulation properties of multiphase systems, such as suspensions and gels, can occur. In all cases, the compendial sterility test requirements described in the various pharmacopoeias must be complied with. 

For sterile Filtration of ophthalmics and small-volume parenteral products it is not unusual to Find several Filters mounted in series. For instance a compounded bulk product may be Filtered through the wall from a dean area into an aseptic filling room. In these cases there are usually two filters mounted in... 

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. 

Blow-fill technology is an aseptic process whereby the container is formed from thermoplastic granules, filled with sterile solution and sealed, all within one automatic operation. The bulk solution should have a low bioburden and is delivered to the machine through a filling system that has been previously sanitized and steam sterilized in situ. Concern has been expressed that the machine itself may generate particles. The plastic granules are composed usually of polyethylene, polypropylene or one of their copolymers and are heat extruded at 200°C into a tube. The two halves of a mould close around this tube and seal the base. The required quantity of sterile fluid is filled into the container, which is then sealed. Products packed in this way include intravenous solutions, and small volume parenteral, ophthalmic and nebulizer solutions. The... 

Finally, a microbiological technical data section is necessary for any NDA for which a sterile claim is being made—this would include such products as large and small volume parenterals and sterile ophthalmic solutions. 

Matthews, B. R. 1999. Recent developments in the European regulation of ophthalmic, parenteral and other sterile products. Eur. J. Parenteral Sci. 4 (3) 103—109. 

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