Dispensing sterile products

USP Chapter <797> is applicable to health care institutions, pharmacies, physician practice facilities, and other facilities where compovmded sterile products are prepared, stored, or dispensed. 

When feasible, compounding procedures are separated from postcompounding quality inspections and review before compounding sterile products is dispensed or administered. 

I. Health care institutions where compounded sterile products are prepared, stored, or dispensed. 

For MPN determination, sterile pipettes calibrated in 0.1-ml increments are used. Other equipment includes sterile screw-top dilution bottles containing 99 ml of water and a rack containing six sets of five lactose broth fermentation tubes. A sterile pipette is used to transfer 1.0-ml portions of the sample into each of five fermentation tubes. This is followed by dispensing 0.1 ml into a second set of five. For the next higher dilution (the third), only 0.01 ml of sample water is required. This small quantity is very difficult to pipette accurately, so 1.0 ml of sample is placed in a dilution bottle containing 99 ml of sterile water and mixed. The 1.0-ml portions containing 0.01 ml of the surface water sample are then pipetted into the third set of five tubes. The fourth set receives 0.1 ml from this same dilution bottle. The process is then carried one more step by transferring 1.0 ml from the first dilution bottle into 99 ml of water in the second for another hundredfold dilution. Portions from this dilution bottle are pipetted into the fifth and sixth tube sets. After incubation (48 h at 35 C), the tubes are examined for gas production and the number of positive reactions for each of the serial dilutions is recorded. 

Each interferon preparation was ultracentrifuged at 20,000 revolutions per minute for one hour to remove tissue debris and inactivated virus. The supernatant was dialyzed against distilled water (1 400) for 24 hours at4°C. The material was then freeze-dried. The dried product was reconstituted in one-tenth of the original volume in distilled water and dispensed into ampoules. Reconstituted solutions were assayed for interferon activity, examined for toxicity, and tested for sterility. 

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. 

Check spore production after 5 days by spore stain. If the percentage of cells sporing is less than 70 to 80%, continue incubation. When a 70 to 80% spore yield is achieved, wash off the growth from the flats with 20 ml of sterile normal saline and dispense into sterile centrifuge tubes. 

As shown in Table 10 New Zealand s own GMP code consists of five parts. The first part covers the manufacture of drug products and the second part the manufacture of blood products. Part 3 covers compounding and dispensing, including compounding of sterile drug products. Part 4 deals with wholesaling and Part 5 with product recalls. Parts 4 and 5 are combined in one document [31]. 

Tor European aseptically produced products with sterile raw materials, where sterile filteration is not carried out, then dispensing and compounding shall be in a grade A area, with a grade B background. 

Risk avoidance. While avoiding risks may sound like a logical approach, it is often impractical for most risks in a business environment. For example, most pharmacies cannot (and would not want to) avoid dispensing prescriptions despite the inherent risks involved in the process. However, there may be situations where not offering a specific good or service with an unreasonable risk may be the most prudent action. Many pharmacies choose simply not to perform sterile compounding services rather than incur the expense and risks associated with the preparation of these products. 

Compounds and dispenses pharmaceuticals including, sterile, chemotherapy, and parenteral nutrition products accurately. 

Using a Pasteur pipette, dispense approximately 1.5 ml aliquots into sterile ampoules (biofreeze vials, Fig. 7.5). These may be blue spot or yellow band, easy snap glass ampoules (Epsom Glass Industries Ltd.) but plastic vials (Nunc, Costar or Sterilin) are now more common. The round bottom vials are difficult to work with and the standard flat bottom vials are very fiddly. Bibby Science Products (Appendix 3) supply a cryogenic work station... 

Solids Some topical drug products such as powders may be considered for marketing in glass bottles with appropriate dispenser. These topical drug products may be sterile and could be subject to microbial limits. 

Diphoterine is a product for chemical spatters on the eye and skin. Prevor Laboratory in France manufactures this odorless, colorless liquid dispensed as an eye wash or skin decontamination spray. It is composed of an aqueous solution to wash many chemical families and pull hydrophilic chemical agents away from the surface of tissues, an amphoteric solution that acts on acids and bases and restores the tissue physiological pH, and a hypertonic solution that stops penetration of corrosive chemicals into tissues. The pH is slightly alkaline (pH 1.2-1.1) and is sterile. Although not classified as such in the USA, it is classified as a medical device in Europe, Canada, Australia, and Brazil (www.prevor.com). 

In the case of an IPC, PQ confirms that all processes supported by the IPC functions operate correctly and deliver the final product. For example, material dispensing systems often require IPCs to support weighing operations within a sterile environment. In this case, PQ can consist of a number of successful weighing operations, documented and compared with the weighing results conducted using a calibrated balance. 

Many isolator applications at the clinical trial scale of manufacturing are based on the same scale of technology used for sterility testing. The aseptic dispensing of pharmaceutical products in hospital pharmacies is also carried out on this scale. Such manufacturing is not carried out on a continuous basis, but in relatively small batches that can be transferred from the isolator with the help of one of the more secure transfer systems. In this type of application, one isolator is being used to dispense a variety of products or several isolators are used for separate tasks. 

Latanoprost Latanoprost (Xalatan) is available as a 0.005% sterile ophthalmic solution in a 2.S-mL dispenser bottle. Latanoprost is also marketed as a combination ophthalmic product with the /3-adrenergic blocking agent timolol, which apparently enhances lOP-lowering by decreasing the production of aqueous humor. Cautions and side effects are similar to those for other ophthalmic prostanoids. 

Part 3 Compounding and Dispensing. Annex 1 Compounding of Sterile Pharmaceutical Products, 1995... 

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