Ophthalmic sterility testing

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. 

Sterility testing is conducted on each lot of ophthalmic product by suitable procedures, as set forth in the appropriate pharmacopeia and validated in each manufacturer s laboratory. While the majority of ophthalmic preparations contain preservatives for multiple-dose use, sterile preparations in special containers for individual use on a single patient must be made available. This availability is especially critical for every hospital, office, or other installation where accidentally or surgically traumatized eyes are treated, as well as for patients intolerant to preservatives. 

Ophthalmic ointments and solutions Sterility test, CCI, AET Test all batches on stability with the exception of the first three batches for AE 0, 12, 24, 36 months... 

All injectable and ophthalmic products with the exception of terminally sterilized product subject to parametric release should undergo Sterility Testing at release. 

Since October 1973, FDA regulations require that all U.S. ophthalmic ointments be sterile. This legal requirement was a result of several surveys on microbial contamination of ophthalmic ointments, and followed reports in Sweden and the United Kingdom of severe eye infections resulting from use of nonsterile ointments. In its survey published in 1973, the FDA found that of 82 batches of ophthalmic ointments tested from 27 manufacturers, 16 batches were contaminated, including 8 antibiotic-containing ointments. The contamination levels were low and were principally molds and yeasts... 

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. 

A specially purified solvent Intended for sterility testing of ophthalmic ointments. 

Several guidelines are available in the literature for the pharmacist who must extemporaneously prepare an ophthalmic solution. The USP contains a section on ophthalmic solutions, as do other compendia and several standard textbooks. Since the pharmacist does not have the facilities to test the product, he or she should dispense only small quantities, with an expiration date of no more than 30 days. Refrigeration of the product should also be required as a precautionary measure. To reduce the largest potential source of microbial contamination, only sterile purified water should be used in compounding ophthalmic solutions. Sterile water for injection, USP, from unopened IV bottles or vials is the highest-quality water available to the pharmacist. Prepackaged sterile water with bacteriostatic agents should not be used. 

The tube can be a source of metal particles and must be cleaned carefully before sterilization. The USP contains a test procedure and limits the level of metal particles in ophthalmic ointments. The total number of metal particles detected under 30 x magnification that are 50 pm or larger in any dimension is counted. The requirements are met if the total number of such particles counted in 10 tubes is not more than 50 and if not more than one tube is found to contain more than 8 such particles. 

Topical, Ophthalmic, and Otic Preparations Clarity, homogeneity, pH, resus-pendability (for lotions), consistency, viscosity, microbial bioburden, and water loss should be tested. For ophthalmic and otic products additional attributes should include sterility, particulate matter, and extractables. 

Ointments have for years presented some problems, since they could not be filtered to eliminate particulate matter they could not be made truly sterile and no adequate tests had been devised to indicate the suitability of added preservatives. In time most of these problems have been solved and sterile, filtered ophthalmic ointments have appeared on the market. These preparation, however, still occupy a position of minor importance. 

However, inherent in these methods are the assumptions that no chro-mogenic substances, other than adrenaline, are present and that the rotatory power of the solutions is due solely to /-adrenaline which precludes their use for routine testing of samples in which the nature of the other materials present is unknown. For such samples Welsh has produced a method in which the adrenaline is converted quantitatively to the triacetyl derivative which may be determined qualitatively as well as quantitatively by polarimetry, and this method has been adopted by the U.S.P, for Epinephrine Solution, Inhalation, Injection, and Sterile Suspension and Epinephrine Bitartrate Ophthalmic Ointment. It is described in detail under Solution of Adrenaline. 

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