Introduction
This guidance addresses recommendations for good sampling practices. Validation sampling plans must be specified or referenced in the protocol.
The purpose of this guidance is to provide guidance on the cGMP requirements for validation sampling. Successful validation is dependent on the proper selection, identification, handling, storage and tracking of test samples. Missed or lost samples can result in the need to repeat a portion of, or the entire, validation study. In order to avoid these types of problems and to ensure data integrity, a number of considerations are listed.
Recommendations and Rationale for Recommendations
cGMP Requirements for Sampling:
The GMPs mention samples, sampling plans, or sampling procedures or methods repeatedly and the main themes that occur throughout these references are as follows:
a) Sampling Plans: Sampling plans and methods shall be predetermined and documented (for example, in a SOP or validation protocol). Sites should be able to provide scientifically sound rationale for the sampling and testing plan. The sampling plan should identify (where appropriate):
– Sampling rationale and acceptance criteria.
– Sample locations, sample size, sample frequency, and types of samplers to be used.
– The tests or evaluations/assessments required and how the data should be analyzed.
– Those qualified parties responsible for taking samples.
– Appropriate container/closure systems to be used, consider the amount of allowable headspace.
– Specific instructions for sampling.
– Any special precautions to be observed, especially with regards to: − Sterile products.
– Hazardous materials.
– Sensitive/labile products (light, temperature, time, oxygen, moisture).
– Mixtures prone to segregation/separation.
b) Number of Samples, Sample Size and Population: Samples should be representative of the population. Some materials may not homogenous due to segregation that occurs during transport, or handling; variability occurring during the manufacturing process; and a variety of other factors that might impact a representative sample. Samples or sampling plans are often based on statistical criteria and the use of an appropriate statistically-based sampling plan can be important to ensure the sample is representative of the population. Each sampling plan should be developed to consider the specific attributes being measured and the risks associated with accepting a defective lot.
– Samples should relate to evaluation of critical quality attributes and the critical process parameters.
– Use sampling plans designed to obtain a representative sample from the product being evaluated or cite reference to an established sampling plan (e.g. site procedure, or ANSI/ASQ standards for inspection of attributes in packaging validation for example).
– Ensure that an adequate amount of sample is available to complete all tests.
The number of tests per sample should be determined in consultation with the laboratory performing the testing and specified in the sampling plan or protocol. One test per sample may be preferable when sample material is inexpensive or there is a risk of cross-contamination when performing multiple tests on the same sample.
– Collect sufficient reserve sample, when possible, (e.g. >2x normal amount) to support potential investigation, except for sterility testing.
c) Sample collection, handling, and identification: Proper sample collection, handling and identification are vital to the success of the validation and the guidance provided by Sampling of Production Materials and Finished Goods should be followed.