Basics of Sterile Compounding: Sterilization Methods in Sterile Product Manufacturing.

Sterilization methods to produce sterile preparations include heat, gas, radiation, and filtration. This article focuses on heat, gas, and radiation sterilization, plus a brief introduction to bright-light sterilization. Microbiology basics and microbial death kinetics, key to understanding why these sterilization methods work, will also be briefly discussed. Filtration sterilization will be covered in a separate article.

Sterile Filtration.

The great majority of sterile products commercially available as well as prepared in compounding pharmacies are sterilized by sterile filtration during aseptic processing. This brief and basic review will highlight the nature, action, and use of sterilizing filters. Special emphasis is given to how filters are validated in producing a sterile filtrate while being compatible with the filtered solution, as well as how filters are integrity tested during aseptic processing.

Documentation: Records and Reports.

This article deals with documentation to include the beginning of documentation, the requirements of Good Manufacturing Practice reports and records, and the steps that can be taken to minimize Good Manufacturing Practice documentation problems. It is important to remember that documentation for 503a compounding involves the Formulation Record, Compounding Record, Standard Operating Procedures, Safety Data Sheets, etc. For 503b outsourcing facilities, compliance with Current Good Manufacturing Practices is required, so this article is applicable to them. For 503a pharmacies, one can see the development and modification of Good Manufacturing Practice and even observe changes as they are occurring in 503a documentation requirements and anticipate that changes will probably continue to occur.

Basics of Sterile Compounding: Particulate Matter.

This article focuses on the requirements for particulate matter in sterile products. Topics include particles and quality, particulate matter standards (large- and small-volume injectables), development of the small-volume injectable test, electronic (light obscuration) and microscope testing, and special requirements for particulate matter in biopharmaceutical preparations.

Basics of Sterile Compounding: Excipients Used in Injections.

This article focuses on the majority of different excipients (all formulation components.

Basics of Sterile Compounding: Manipulating Peptides and Proteins.

Biopharmaceuticals contain primary and secondary structure, which offer few problems. It is the tertiary structure that causes problems, resulting in both physical and chemical stability issues. The thrust of this article is to share briefly what can be done to minimize these problems.

Basics of Sterile Compounding: Biopharmaceutics of Injectable Dosage Forms.

Biopharmaceutics studies the relationship between the drug product and what happens after the product is administered. Since the majority of injectables are administered by the intravenous route, thus avoiding the need for drug absorption, not many articles are published compared to other routes of drug administration. However, other routes of administration for drug injection are becoming more frequent because of greater commercial availability of sustained- and controlled-release drug delivery systems. This article reviews basic principles of drug absorption, distribution, metabolism, and elimination of injectable drugs and certain physicochemical and physiological factors affecting injectable drug biopharmaceutics.

Accuracy Considerations in Sterile Compounding.

Published information about the accuracy of filling and closing operations of sterile products is limited and guidelines on the topic are very general. This article highlights the basic principles in sterile-product filling of syringes and vials. Also covered in this article are descriptions of some of the available devices for filling containers, a brief discussion of the advances in vial and syringe filling, a discussion on the advantages and disadvantages of sterile product filling methods, and a discussion on possible problems encountered during filling operations. Because of the extremely high costs of some new drugs, especially biopharmaceuticals, compounding pharmacies may prefer to fill small batches to reduce the risk of unacceptable monetary losses in the event of a manufacturing deviation that results in batch rejection.

Formulation and Stability of Solutions.

Ready-to-use solutions are the most preferable and most common dosage forms for injectable and topical ophthalmic products. Drugs formulated as solution almost always have chemical and physical stability challenges as well as solubility limitations and the need to prevent inadvertent microbial contamination issues. The first in this series of articles took us through a discussion of optimizing the physical stability of solutions. This article concludes this series of articles with a discussion on foreign particles, protein aggregation, and immunogenicity; optimizing microbiological activity; and osmolality (tonicity) agents, and discusses how these challenges and issues are addressed.

Formulation and Stability of Solutions.

Ready-to-use solutions are the most preferable and most common dosage forms for injectable and topical ophthalmic products. Drugs formulated as solution almost always have chemical and physical stability challenges as well as solubility limitations and the need to prevent inadvertent microbial contamination issues. This article, which takes us through a discussion of optimizing the physical stability of solutions, represents the first of a series of articles discussing how these challenges and issues are addressed.

Basic Principles of Lyophilization, Part 2.

The achievement of a high-quality lyophilized (freeze-dried) dosage form involves the combination of optimal formulation design and optimal freeze-dry cycle design. Part 1 of this 2-part article discussed the basic principles and procedures of lyophilization up to a discussion on the different stages of lyophilization. The stages of lyophilization are discussed within this article.

Current Perspectives on the Syringe Delivery System.

An article on the topic of sterile product packaging and delivery systems was published in the November/December 2015 issue of the International Journal of Pharmaceutical Compounding. This article expands the discussion on the syringe packaging system and provides more detail about the history, changes, challenges, and use of syringes in the compounding pharmacy.

Basics of Sterile Compounding: Clinical Hazards of Injectable Drug Administration.

Injections of drug products are generally considered safe when performed by qualified personnel. However, there always exists a low finite probability of risk with any injectable product by any injectable route of administration. This article briefly reviews potential risks of injectable drug administration.

Basics of Sterile Compounding: Personnel Requirements for Sterile Compounding.

The risk of microbial contamination during sterile product preparation would be practically non-existent were people not involved in the preparatory process. This article discusses why people are the main source of microbial contamination and what safeguards need to be present to minimize this source.

Contamination Control.

There are serious consequences if contamination control is not enforced and contaminated products/preparations are released to the market. The greatest risk of microbial contamination is exposure of sterile (also termed "critical") sites to potential sources of contamination. Contamination control basically involves at least fourteen entities to control or that help to determine the extent (quality) of control. Some of these entities are covered in this article; others will be covered in subsequent articles by the author.

Quality Assurance and Quality Control, Part 2.

The tragedy surrounding the New England Compounding Center and contaminated steroid syringe preparations clearly points out what can happen if quality-assurance and quality-control procedures are not strictly practiced in the compounding of sterile preparations. This article is part 2 of a two-part article on requirements to comply with United States Pharmacopeia general chapters <797> and <1163> with respect to quality assurance of compounded sterile preparations. Part 1 covered documentation requirements, inspection procedures, compounding accuracy checks, and part of a discussion on bacterial endotoxin testing. Part 2 covers sterility testing, the completion from part 1 on bacterial endotoxin testing, a brief dicussion of United States Pharmacopeia <1163>, and advances in pharmaceutical quality systems.

Quality Assurance and Quality Control, Part 1.

The tragedy surrounding the New England Compounding Center and contaminated steroid syringe preparations clearly points out what can happen if quality-assurance and quality-control procedures are not strictly practiced in the compounding of sterile preparations. This article represents part 1 of a 2-part article on quality-assurance and quality-control procedures and serves as an introduction to the topic of finished preparation release checks and tests. Part 1 highlights what is required to comply with United States Pharmacopeia General Chapter <797>, and part 2 continues with a discussion on the requirements of <797> as well as what is required in chapter < 1163> with respect to quality assurance of compounded sterile preparations. Written procedures, good documentation practices, and specific details for clarity, sterility, and bacterial endotoxin (pyrogen) testing are presented in this article.

BASICS OF STERILE COMPOUNDING: Sterilization Methods in Sterile Product Manufacturing.

Sterilization methods to produce sterile preparations include heat, gas, radiation, and filtration. This article focuses on heat, gas, and radiation sterilization, plus a brief introduction to bright-light sterilization. Microbiology basics and microbial death kinetics, key to understanding why these sterilization methods work, will also be briefly discussed. Filtration sterilization will be covered in a separate article.

BASICS OF STERILE COMPOUNDING: Barrier Isolator Technologies in Aseptic Processing.

Barrier isolator technologies have made significant contributions to the advancement of aseptic processing and the increased level of sterility assurance. This article discusses why this is so and provides brief information about types of isolators, isolator attributes, isolator challenges, and considerations in isolator design, implementation, and validation.

Basics of sterile compounding: aseptic processing.

This article discusses factors that affect the assurance of sterility of an aseptic process operation and balances what is required/practiced in the pharmaceutical industry via the U.S. Food and Drug Administration and European aseptic processing guidelines and what is required/practiced in compounding pharmacies via the United States Pharmacopeia (USP) General Chapter <797>.