Sterile & Non-Sterile Pharmaceutical Products

Sterile pharmaceutical products are defined as sensitive pharmaceutical products that should be free from living micro-organisms, pyrogens and unacceptable particulate matter including contaminants during and after their production. Parenteral products are typical examples of sterile pharmaceutical products; and they are radically different from other dosage form in terms of standards of purity and safety.

Some pharmaceutical products require utmost sterility and high level of decontamination during their production process, and as such are called sterile pharmaceutical products (e.g., parenteral products). On the other hand, some other pharmaceutical products may not require very stringent process of sterility during their production and are referred to as non-sterile pharmaceutical products (e.g., lotions or ointments).

Pharmaceutical products are divided into two groups:

• Sterile pharmaceutical products

• Non-sterile pharmaceutical products

Sterile pharmaceutical products are pharmaceutical preparations that are critical and highly sensitive in nature due to their close contact with internal body tissues, organs and bloodstream. Sterile pharmaceutical products are produced or manufactured under conditions and environments that remove any forms of microbiological contamination.

The production processes of sterile pharmaceutical products have a clear regulation and guidelines that directs their production. They are mainly used for invasive therapy. Sterile pharmaceutical products are totally free from contaminating microorganisms, pyrogens, living microorganisms, fungi, bacteria and viruses.

This group of pharmaceutical products (i.e., sterile pharmaceutical products) are prepared or manufactured under strict sterile conditions. A high standard of purity and safety is usually maintained during their production. During the preparation of sterile pharmaceutical products, strict aseptic techniques and quality control, as well as quality assurance procedures are applied at every stages of the production process in order to ensure that the finished (final) product is safe, of good hygiene and is of good quality. Sterile pharmaceutical products are produced under very strict compounding.

Sterile compounding is defined as the preparation of drugs or pharmaceutical products (intended for human or animal sue) in an environment and conditions free from bacteria, viruses, or any other potentially infectious microorganisms. It is used for the pharmaceutical preparations that will be administered either through an intravenous (IV) route, or though injections. Sterile pharmaceutical compounds prepared this why can be applied directly into the eyes of the patient.

For example, the main reasons for ensuring good sterile preparations according to the United States Pharmacopeia (USP) are to describe conditions and practices that can prevent the following types of patient harm as a result of the use of sterile pharmaceutical products on the patient.

• Microbial contamination.

• Excessive bacterial endotoxins.

• Unacceptable variability in intended strength of ingredients.

• Unintended chemical/physical contaminants.

• Ingredients of inappropriate quality in compounded sterile preparations (CSPs). 

Uses of sterile pharmaceutical products

• They are compounded to be used as injections.

• They are used as infusions.

• They are used for ophthalmic applications such as in eye drops or ointments.

• They are used for surgical procedures and other medical procedures that are invasive and make contact with the bloodstream.

Non-sterile pharmaceutical products are pharmaceutical preparations that are produced under conditions that only or barely minimize microbiological contamination of the process or finished products. The processes involved in the production of non-sterile pharmaceutical products are not strictly monitored as is the case during the production of sterile pharmaceutical products. For non-sterile pharmaceutical products, the following microorganisms are representative indicator microorganisms usually detected by the quality control process:

• Escherichia coli

• Pseudomonas aeruginosa

• Staphylococcus aureus

• Clostridium

• Salmonella

• Candida albicans

Examples of sterile pharmaceutical products

• Injections (e.g., intravenous additives, total parental nutrition)

• Non-injectable sterile water

• Ophthalmic preparations (e.g., eye drops, eye ointment, eye lotions, contact lenses solutions, cleaning solutions, wetting solutions)

• Dressings

• Surgical materials

• Implants

• Absorbable haemostats

• Surgical ligatures & sutures

• Medical instruments & equipment (e.g., pacemakers, needles, scissors, forceps, catheters, kidney dialysis equipment)

Examples of non-sterile pharmaceutical products

• Solutions

• Creams

• Tablets

• Capsules

• Suspensions

• Ointments

• Syrups

• Powders

• Suppositories

Suppositories are pharmaceutical preparations or products that carry drugs administered through the vagina or rectum. They are generally forms of medicines that are inserted into the vagina, rectum and urethra. After insertion, the suppository melts or dissolves at a particular temperature, and after which the drug is released and absorbed into the body or bloodstream.

Critical factors to consider in the production of sterile pharmaceutical products

• Bioburden of product. Bioburden is defined as an estimate of the total viable count of microorganisms present in the product.

• Sterility level of product. All sterile pharmaceutical products must be sterile and free from contaminating microorganisms or their by-products.

• Parameter release

• Presence of pyrogens. Pyrogens are fever-causing by-products of microorganisms. They must not be found in sterile pharmaceutical products. LAL test can be used in detecting the presence of pyrogens in sterile pharmaceutical products.

Generally, parenteral drug delivery systems and many medicinal products, such as dressings and sutures, must be sterile in order to avoid the possibilities of microbial degradation or infection occurring as a result of their use. Sterility is also important for any material or instrument likely to contact broken skin or internal organs.

Although pathogenic bacteria, fungi or viruses pose the most obvious danger to a patient, it should be also realized that micro-organisms usually regarded as non-pathogenic and which inadvertently gain access to body cavities in sufficient numbers may cause a severe, possibly fatal infection. Consequently, injections, ophthalmic preparations, irrigation fluids, dialysis solutions, sutures and ligatures, implants, and certain surgical dressings, as well as instruments necessary for their use or administration, must be presented in a sterile condition.

Although there is always a chance of an idiosyncratic reaction between a medicine and a patient caused by sensitivity, allergic reaction or unwanted side effects, for sterile products there is the added requirement that they must be free of viable microorganisms. This consequently means the product should be manufactured in a manner that reduces to the lowest likelihood the risk of microbial contamination. Thus a sterile product should not contain viable bacteria, yeasts or fungi, nor other microorganisms such as rickettsiae, mycoplasmas, protozoa or viruses. 

Sterilization processes concentrate on the destruction or removal of microorganisms. Each process is designed to remove the most problematic microorganism (i.e. the smallest bacteria in filtration or the most heat-resistant bacterial spores in heat sterilization processes) on the basis that, once a sterilization process has been chosen, elimination of the most problematic species will have led to the elimination of all less resistant microorganisms.

The choice of the method of sterilization to use during the production process of a sterile or non-sterile pharmaceutical product is determined largely by the ability of the formulation and container to withstand the physical stresses applied during the sterilization process. All products intended for sterilization should be manufactured under clean conditions and therefore will be of low microbial content (bioburden) prior to sterilization. Under these conditions, the sterilization process will not be overtaxed and will generally be within the safety limits needed to provide the required level of sterility assurance.

References

Arora D.R (2004). Quality assurance in microbiology. Indian J Med Microbiol, 22:81-86.

Ashutosh Kar (2008). Pharmaceutical Microbiology, 1^st edition. New Age International Publishers: New Delhi, India. 

Axelsen P.H (2002). Essentials of antimicrobial pharmacology. Humana Press, Totowa, New Jersey, USA. Al-Jasser A.M (2006). Extended – Spectrum Beta – Lactamases (ESBLs): A Global Problem. Kuwait Medical Journal, 38(3):171-185.

Denyer S.P., Hodges N.A and Gorman S.P (2004). Pharmaceutical Microbiology. 7^th ed. Blackwell Publishing Company, USA.

Joslyn, L. J. (2000). Sterilization by Heat. In S. S. Block (Ed.), Disinfection, Sterilization, and Preservation (5th ed., pp. 695-728). Philadelphia, USA: Lippincott Williams and Wilkins.

Nally J.D (Ed.) (2007). Good manufacturing practices for pharmaceuticals. Sixth edition. Informa Healthcare USA, Inc, New York.

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