Fact Sheet: Overview of Preservative Efficacy Testing

Description:
•    Pharmacopoeial standards require multi-dose pharmaceutical products to contain antimicrobial preservatives in order to protect against microbial growth. Multi dose products will also require preservative efficacy testing (PET), also known as antimicrobial efficacy (AET), to ensure the safety of the product throughout its life cycle.
•    Antimicrobial preservatives are added to pharmaceuticals, medical devices, personal care products, cosmetics and food products to inhibit the growth of microorganisms. These microorganisms may be inadvertently introduced during the manufacturing process or during the use of products with multiple-dose containers.

Preservative Efficacy Testing Overview:
•    Limiting the growth of microorganisms in various products helps to prevent them from spoilage and protects the users from possible infections.
•    A few factors can determine the efficacy of a preservative, including the active component of the product, the formulation in which it is incorporated, or the container / packaging in which the product is enclosed.
•    Another regulatory requirement of drug development and manufacturing is guaranteeing that no inappropriate organisms are able to sustain themselves within the product or its packaging.
•    When considering the regulation and validation of pharmaceutical products, efficacy of the active pharmaceutical ingredient (API) is often the main concern. Ensuring that this compound elicits the appropriate effect at the correct target site is of vital importance.
•    Efficacy is evaluated by challenging the preparation with a suitable range of microorganisms. Samples are taken at set time intervals and any organisms that remain are enumerated.
•    For example, a topical cream contained in a pot (which the user dips fingers into) will be affected differently to a cream contained in a tube applied directly to the skin. If any of the components change, it is necessary to re-evaluate how the preservatives will continue to perform.

In the Lab / at Wickham Micro Ltd:
•    PET is required by the British, European and United States pharmacopoeial standards and is often carried out in dedicated testing laboratories, due to their unique set up and the manual requirements of the test.
•    Before any PET testing can be carried out, validation / method suitability must be completed. For this, the sample is purposefully inoculated with a challenge organism, to check if there is a suitable recovery against a control.
•    To ensure any preservatives are compatible with the formulation, PET should be conducted as soon as possible after the manufacture of a new product with a second challenge test recommended a few months later to check whether the preservative has broken down and lost effectiveness over time.
•    It is also crucial to revisit PET whenever the formulation, manufacturing process or packaging of an existing product changes, as any of these can impact preservative performance.
•    Often, PET may be conducted at the same time as a stability test, which provides the information necessary to demonstrate that a product’s efficacy lasts throughout the storage process. When samples are pooled at specific time points in a stability test, PET is carried out as well to track the performance of the preservative over the course of the stability programme.
•    Some larger scale projects may require a spacious facility to set out numerous plates for multiple organism challenges across many time points.
•    At Wickham Laboratories, our extensive in-house culture collection enablse us to offer efficacy studies following pharmacopoeial requirements, or customised to a client’s individual requirements. We carry out both validation and analysis to assess the efficacy of preservation systems across a wide range of product types including parental, ophthalmic, topical or oral.