Sterile Parenteral Flashcards
What are the critical quality attributes for a parenteral product? Why is pH important? Why is endotoxin important?
Sterile, particulate free, endotoxin fee, viscosity, pH.
The target pH should be as close as possible to physiological pH. The acceptable range is pH 2–11 for intravenous and intramuscular injection. It is pH 4-9 for subcutaneously injection due to potential irritation issue.
pH is a critical factor for all those medications prepared as aqueous liquid forms, because it has an impact on the solubility of the molecule, determining the stability of medications, the biological tolerability of the formulation, and the activity of the molecule.
Endotoxin is important as its presence can cause sepsis, toxic shock, death
What are the critical quality attributes for a parenteral product?
Sterile
Free from Particulates
Bioburden
Endotoxin
Why is pH important in a parenteral product?
The acceptable range is pH 2–11 for IV and intramuscular injections, and pH 4-9 for subcutaneous injection due to potential irritation issues
Why is endotoxin important in a parenteral product?
Endotoxins can induce fever and inflammation in patients and in some cases can lead to anaphylactic shock or death.
Parenteral preparations may contain
suitable excipients, for example to adjust the tonicity of the preparation relative to blood, to adjust or stabilise the pH, to increase the solubility of the active substances, to stabilise the preparation or to provide adequate antimicrobial properties. The excipients do not adversely affect the intended medicinal action or, at the concentrations used, cause toxicity or undue local irritation.
Parenteral container closures ensure:
a good seal, prevent micro-organisms and other contaminants from entering the container and closure system and usually permit the withdrawal of a part or all of the contents without the closure being removed. Closures for multidose containers are sufficiently elastic to ensure that the puncture is resealed when the needle is withdrawn.
Parenteral - Particulate contamination: sub-visible particles
Liquid preparations for injection or infusion, if applicable after reconstitution, comply with the test. Unless otherwise justified and authorised, suspensions, emulsions and gels for injection comply with the test.
In the case of preparations for subcutaneous or intramuscular injection, higher limits may be appropriate. Radiopharmaceutical preparations are exempt from these requirements. Preparations for which the label states that the product is to be used with a final filter are exempt from these requirements, providing it has been demonstrated that the filtrate complies with the test.
For preparations for veterinary use, when supplied in containers with a nominal content of more than 100 mL and when the content is equivalent to a dose of more than 1.4 mL per kilogram of body mass, liquid preparations for injection or infusion, if applicable after reconstitution, comply with the test for particulate contamination: sub-visible particles.
Parenteral - Particulate contamination: visible particles
Liquid preparations for injection or infusion, if applicable after reconstitution, examined under suitable conditions of visibility, are practically free from visible particles.
Preparations for which the label states that the product is to be used with a final filter are exempt from these requirements, providing it has been demonstrated that the filtrate complies with the test.
Parenteral - Bacterial endotoxins - pyrogens
Parenteral preparations for human use, if applicable after reconstitution or dilution, comply with the test for bacterial endotoxins or, where justified and authorised, with the test for pyrogens.
Where the label states that the preparation is free from bacterial endotoxins or that it is apyrogenic, the preparation complies with the test for bacterial endotoxins or with the test for pyrogens, respectively.
Parenteral preparations for veterinary use comply with the test for bacterial endotoxins or with the test for pyrogens when the volume to be injected in a single dose is 15 mL or more and is equivalent to a dose of 0.2 mL or more per kilogram of body mass.
Parenteral labelling
The label states:
— the name and concentration of any added preservative;
— where applicable, that the solution is to be used with a final filter;
— where applicable, that the preparation is free from bacterial endotoxins or that it is apyrogenic.
No preservative is added to parenteral injections when:
— the volume to be injected in a single dose exceeds 15 mL, unless otherwise justified;
— the injection is intended for administration by routes where, for medical reasons, a preservative is not acceptable, such as intracisternally, epidurally, intrathecally or by any route giving access to the cerebrospinal fluid, or intra- or retro-ocularly.
Such preparations are supplied in single-dose containers.
Parenteral tests
Uniformity of dosage units
Uniformity of content
Uniformity of mass
