Sampling of Raw Material used in the Pharmaceutical Drug Product Preparation
Each of the raw material used in the preparation of pharmaceutical drug products plays a vital role as it directly affects the quality of final drug product so in order to achieve the right quality of final product evaluation of all the raw material should be done in a right manner. In the evaluation of raw material, sampling of the subjected raw material is very essential which can directly affect the analytical results of the raw materials. So understand here apart from the right sampling tools what are the other things where we need to focus; As you know if any cross-contamination happened into the raw material then the exact result of the raw material cannot be produced so to avoid any cross-contamination a Uni-directional airflow is required which can be achieved by only uni-directional airflow system or booth.
UNI-DIRECTIONAL AIRFLOW SYSTEM/BOOTH
As mentioned above uni-directional airflow system is used to avoid any cross-contamination in the raw material with its uni-directional airflow. Apart from avoiding cross-contamination UDAF (uni-directional airflow system) is used for the operator safety from materials. Dust containment or uni-directional airflow can be shown through smoke study and through a video recording. Its uni-directional airflow is maintained through a defined air velocity. As per WHO TRS 961 Annex 5, unidirectional airflow system air velocity should be 0.36 to 0.54 m/s, this value of air velocity is required in the UDAF system where grade A environment is required which is generally used to dispense sterile materials. Due to the air velocity weighing balance sensitivity should not be disturbed so if Grade A environment is not required to dispense or sampling the raw materials like in case of oral solid dosages or non-sterile external preparation then air velocity of UDAF booth can be reduced so that weighing balance sensitivity could not be disturbed. Where lower velocity is required then the prescribed limit, uni-directional airflow system can be called as Air protection booth (APB). During dispensing or sampling of raw materials, the operator should be standing in a safe zone area where airflow should not be disturbed.
If the operator blocks the path of airflow it could lead contamination to the material which could further affect the final drug product quality.
There should not be any obstruction in the path of airflow so it is suggested that minimum 100 mm gaps are required between return air riser and weighing balance platform so that air can be easily passed and weighing balance reading should not be disturbed. Apart from the above uni-directional airflow system, a detailed procedure on the sampling of raw material is required which comprises following but not limited to;
- Sampling tools based on the container size & raw material nature.
- Sampling technique based on the nature of material like some material required shaking/ heating (in case of suspension or material which have some solid material in the liquid phase).
- Light sensitive material details and its sampling technique.
- Sampling plan; selection of sample size, sample container, etc.
- Labeling procedure on the sampled containers and other containers.
- Representative sample quantity sufficient for testing as per specification requirement.
Sampling plan and procedure should be defined in a manner so that any non-uniformity within the material can be detected and attention should be paid on any sign of the non-uniformity in the material during sampling of raw material, it can be detected through shape, color, and size of material particles (crystalline, amorphous, granular, etc.)
To avoid the masking the contamination and other quality problem sample pooling from different portion should be avoided. Now understand the sampling plan. As per the WHO technical series no. 929, annex-4 following sampling plan can be followed;
The n-sampling Plan
This n-plan of sampling can be used when you know that materials are procured from approved and recognized source and sample considered as uniform. In n-plan sample could be withdrawn from any part of the material container, usually from the top layer of the container. The following formula shall be used to decide the sampling plan n= 1 + √N where N means the number of sampling units in the consignment. suppose if 90 container received in consignment the sampling plan shall be decide as follow n = 1 + √N n = 1 + 9.48 n = 10.48 rounding number 10 n value shall be decide by simple rounding. If the total container in consignment is equal to or not more than 4 then the sample shall be withdrawn from each of the containers. Identification test of material from each of the sampled container needs to be done and once identification test meet requirement against specification then original sample can be combined to make it composite for further analysis and rest can be kept as a retention sample.n-Plan is not suggested to use by laboratories required to analyze and release or reject the consignment which is used in final product processing.
The p-sampling Plan
This p- sampling plan is also used when you know that material is procured from approved and recognized sources and its main purpose is to test the identity of the material. Sampling size for p-plan shall be decided based on the below formula;p = 0.4 √N where N means the number of the sampling unit. Suppose if total 25 containers received in consignment then sample size shall be calculated as;p = 0.4 x 5p = 2 Figure of p is obtained by rounding up to the next highest integer number, With this plan sample shall be taken from each of the N sampling units of the consignment and keep in separate containers and all these samples visually inspected and tested for identity, if results found compliant then p- final samples are formed by appropriate pooling of the original sample.
The r-sampling Plan
As per the WHO-TRS 929 annex-4, r-plan shall be used only when a material is suspected as non-uniform and procured from any non-recognized source like ayurvedic or herbal medicinal product used to manufactured product where even therapeutic agent is not equally distributed in any part of herbal plants so in that case r-plan can be used by following the below formula;r = 1.5 √N where N is sampling units Figure of “r” are obtained by rounding up to the next highest integer number. In this r-plan sample shall be collected from each of the N sampling units of the consignment and keep in the separate sample container. All these original samples are transferred to laboratories for identity test and if results are concordant then the r-sample are selected randomly and individually tested and if all the results are concordant then all r- samples are combined for retention sample.
I hope above mention all the details will help you to elaborate your raw material sampling procedure w.r.t. sampling plan and precaution during sampling by using a unidirectional airflow system/ booth or APB (Air protection booth).
1. WHO technical report series no. 929, 2005 Annex 4 WHO guideline for the sampling of pharmaceutical products and related materials
2. WHO technical report series no. 961, 2011 Annex 5 Supplementary guideline on good manufacturing practices for heating, ventilation, and air conditioning system for non-sterile pharmaceutical dosages form.