Quality Control is an essential function of the pharmaceutical industry. Drug manufacturers must thoroughly test materials, processes, equipment, techniques, environments and personnel in order to ensure their final products are consistent, safe, effective and predictable.
“Undoubtedly, a company suffers enormous damage when a drug product is recalled.”PharmacopeiasIn addition to their local government authorities, many pharmaceutical manufacturers look to a Pharmacopeia for guidance on ensuring the quality, safety and benefit of the medicines they produce. A Pharmacopeia is an organization that develops and publishes standards for manufacturing prescription and over-the-counter medicines as well as other healthcare products.
Three major Pharmacopeias throughout the world include: the United States Pharmacopeia (USP), the European Pharmacopoeia (Ph. Eur.) and the Japanese Pharmacopoeia (JP). Each of these organizations has their own set of standards, however the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is working to facilitate international harmonization in the interpretation and application of technical guidelines and requirements for the pharmaceutical industry.
The growth promotion testThe Growth Promotion Test is a very important Quality Control function in the pharmaceutical industry. It is imperative for establishing the nutritive properties of the microbiological culture medium that will be used in a pharmacopeial procedure, such as a test for specified microorganisms. Culture medium (or media) refers to a liquid or gel substance that is used to support the growth of microorganism or cell.
The Growth Promotion Test is necessary to ensure that the culture medium is able to support the growth of small numbers of microorganisms, and that selective medium will grow specified microorganisms. If the new batch of media is not able to properly support growth, the pharmacopeial tests for which it is used will fail.
“The overall costs associated with a major drug recall are almost immeasurable.”
There are three key tests in the pharmacopeias that outline growth promotion testing. These chapters have been harmonized in the United States Pharmacopeia (USP), the European Pharmacopoeia (Ph. Eur.) and the Japanese Pharmacopoeia (JP).
Microbial enumeration testsThis test establishes the ability of the new lots of medium to support growth when the inoculum contains a small number of microorganisms. This test is used for both solid and liquid media.
Tests for specified microorganismsThis test establishes the ability of the selective medium to meet three criteria:
• Growth promoting properties – the growth of selected microorganism is supported
• Indicative properties – the colonies have specific morphological characteristics (see figure1)
• Inhibitory properties – organisms that should be inhibited on the medium should not grow
Sterility testsThis test establishes the ability of new lots of medium to support growth when the inoculum contains a small number of microorganisms. This test is used for liquid medium only.
Requirements of the growth promotion testGrowth promotion testing must be done for each and every new batch of culture medium, both solid and liquid, that will be used in a Pharmacopeial procedure. This includes purchased pre-prepared or dehydrated medium, or medium that was prepared in house. At a minimum, the testing must be done with the list of organisms specified in the pharmacopeia. Additional organisms may be needed depending on the requirements and SOPs for each individual laboratory or situation.
“Growth promotion testing must be done for each and every new batch of culture medium, both solid and liquid…”The basic requirements for the GPT are as follows:
1. The new batch of medium must be inoculated with a small number of microorganisms (less than 100 Colony Forming Units).
2. The laboratory should test the medium with the microorganisms required by the pharmacopoeias.
3. The microorganisms must not be more than five passages removed from Reference Culture (also called the original master seed lot).
In order for the new batch of medium to be approved for use, growth on the new batch of medium must be comparable to growth obtained on a batch of medium previously approved by the laboratory (see figure 2).
Microorganisms for growth promotion testing
The challenge microorganisms for use in Growth Promotion Testing can be purchased from a culture collection, or from a licensed commercial manufacturer.
The use of strains directly from a culture collection requires the construction of a calibration curve for each organism, because each organism will have a different curve. This can be done using McFarland standards to visually approximate and interpret turbidity of a cell suspension, or by using a spectrophotometer to directly measure turbidity of the cell suspension.
“If the new batch of media is not able to properly support growth, the pharmacopeial tests for which it is used will fail.”These methods are very time consuming, and must be done over a number of days because incubation is required for the growth of the organism. The use of McFarland standards also introduces significant variability because this is a subjective measurement.
Ready-to-use certified strains are available as quantitative preparations. These samples can be used with only a few quick and simple steps. Using these preparations will save time because no growth time is required, and hands -on work time is reduced by eliminating the need for any measurement or interpretation of cell density. An additional benefit is the reduced risk of contamination of the sample and in the environment because the use of the prepared strains is short term.
Quality control is an essential part of the laboratory routine. It is not only important for compliance with standards, but also reduces risk to the end user, and, consequently, to the manufacturer.
Source: pharmaphorum
