Sterile Product Theory Exam Review

Sterile Product Theory Final Exam Review

• History of Sterile Products:

  • 1616: William Harvey described blood circulation.
  • 1665: Christopher Wren successfully injected opium.
  • 18th-19th centuries: Bacterial growth and sepsis discovered.
  • Late 19th century: Sterilization methods improved.
  • 1923: Florence Seibert discovered pyrogens from water.
  • 1926: First official injection solutions added.
  • 1960s: Infusion technology advancements.
  • 1971: Contaminated IV solutions caused outbreaks.

• Standards and Guidelines:

  • Health Canada: Created policy on manufacturing and compounding drug products in Canada. Defines terms like "compounding" and "manufacturing". Compoundings of sterile products fall under section 'C' of the Act and includes drugs scheduled in Schedule C, D. Health Canada's GMP (Good Manufacturing Practices) will be regulated and include site inspections by each provincial regulatory authority.
  • NAPRA: Developed standards for pharmacy compounding of hazardous/non-hazardous sterile preparations. Adapted standards from USP <797>.
  • CSHP: Created guidelines for preparation of sterile products in pharmacies. Ensures compliance with Food and Drug Act and Health Canada's GMP.
  • OCP: Adopted NAPRA standards to be followed by pharmacies engaging in sterile compounding. Now, all pharmacies involved are inspected by OCP.

Risk Levels (USP Chapter 797)

• Low Risk: Compounding under ISO Class 5 environment using commercially available ingredients, products, components, & devices. Simple aseptic opening and transfer/measuring 3 sterile commercial products and 2 entries into any one container. Storage limited to 48 hours or less at room temperature, 14 days or less refrigeration, or 45 days or less in frozen state. Sterility test not required in these parameters.
• Medium Risk: Low risk level conditions + combining/pooling multiple doses of commercial products for multiple patients. Complex aseptic manipulations and longer duration compounding times. Storage limited to 30 hours or less at room temperature, 9 days or less refrigeration, or 45 days or less in frozen state. Sterility testing not required.
• High Risk: Use of non-sterile ingredients or devices. Exposure to outside of ISO Class 5 environment (more than one hour). Inappropriate gloving and gowning. Storage limited to 24 hours or less at room temperature, 3 days or less refrigeration, or 45 days or less in frozen state. Sterility testing not required.

Characteristics of Sterile Products

• Sterility: Absence of viable microorganisms. Lower SAL values indicate greater assurance of sterility.
• Particulate Matter: Absence of particulate matter like hair and dust.
• Pyrogenicity: Absence of pyrogens (fever-producing endotoxins).
• Stability: Prevention of drug degradation due to oxidation, hydrolysis, or polymerization.
• Viscosity: Key characteristic of ophthalmic preparations. Important to increase contact time and solution surface.
• pH: Typically 3-8 for injections, ideal close to 7.4. Maintaining pH ensures stability.
• Tonicity: Must simulate the same tonicity as blood (isotonic, hypertonic, or hypotonic). Tonicity adjusted using sodium chloride, matching tear pH.

Sterile Parenteral Dosage Forms

• Injections: Includes aqueous and non-aqueous sterile products delivered via IV, IM, SC, ID, IT, and IS.
• Ophthalmics: Solutions, suspensions, and ointments for eye use.
• Dialysates: Sterile, isotonic solutions for kidney failure treatments (hemodialysis and peritoneal dialysis).
• Irrigations: Solutions used to bathe or flush wounds/organs.
• Radiopharmaceuticals: Radioactive chemicals for diagnosing conditions.

Viruses, Pyrogens, and Removal of Pyrogens

• Viruses: Not common contaminants of sterile products. Cannot reproduce on their own.
• Pyrogens: Fever-producing substances, mostly from bacteria. Difficult to eliminate once present.
• Removal of Pyrogens:
  • Aseptic technique
  • De-pyrogenation and sterilization of equipment
  • Use of pyrogen-free sterile ingredients, equipment, and closures.

Sterilization, Disinfection, Disinfectants, Antiseptics, and Antisepsis

• Sterilization: Process eliminating all microbial life from an object or surface; more potent than disinfection.
• Disinfection: Reduces microbial numbers but doesn't always destroy spores.
• Disinfectant: Chemical agent to reduce microorganisms on inanimate surfaces.
• Antiseptic: Chemical agent used to kill microorganisms on living tissue.
• Antisepsis: Process of using antiseptics to kill microorganisms

Other Types of Infections (e.g., transmission and common pathogens)

• Direct: Skin-to-skin or mucous membrane contact
• Airborne: Respiratory secretions like coughs and sneezes
• Fecal-oral: Contaminated food or water
• Fomites: Inanimate objects carrying pathogens from contaminated surfaces
• Community acquired: common infections contracted outside of healthcare settings.
• Nosocomial: infections acquired during a hospital stay.
• Iatrogenic: infection acquired as a result of a medical treatment or procedure.

Contamination Control in Facilities

• Requirements: Specific areas for all aspects of sterile compounding (including controlled rooms that have certain conditions).
• Engineering requirements: Air-handling/temperature/humidity control in specific areas to keep contamination from entering or leaving an area. Strict traffic control. Personnel must participate in controlled training for personal protective equipment, preparation, and procedures involved with sterile room work.

Anterooms vs. Cleanrooms

• Anteroom: Buffer zone between uncontrolled and less controlled areas. For preparation of personnel, supplies, and materials prior to entering a cleanroom for compounding.
• Cleanroom: Primary workspace for sterile compounding. Contains visible demarcation line.
  • Contains PECs (primary engineering controls).
  • Uses HEPA filters to remove contaminants, keep air under positive pressure.
  • Designed to minimize contamination with strict materials controls.

Laminar Airflow and Critical sites

• Laminar Airflow: Unidirectional airflow from HEPA filters to work surfaces.
• Critical sites: Any opening or surface that can provide a passageway between the sterile product and surrounding environment (e.g., injection/syringe entry points, luer-lock connectors).

Types of Sterile Products

• Vials: Single-use or multi-dose vials.
• Ampules: Single-use glass ampoules containing a powder or liquid that must be reconstituted before use.
• Double-chambered vials: Sterile powder and diluent compartments in a single container.

Dispensing Devices and Filtering Devices

• Dispensing Devices: Devices to remove solutions, prevent multiple needles punctures.
• Filters: Using various filters to sterilize solutions in vials, and for pressure equalization in vials and bags.

Methods of Sterilization

• Methods:

  • Cold
  • Dry Heat
  • Moist Heat (autoclaving, freeze-drying)
  • Filtration

• Chemical Methods:

  • Phenols
  • Alcohols
  • Biguanides
  • Aldehydes
  • Hydrogen Peroxide
  • Peracetic Acid