Pharmaceutical sampling procedures for non-sterile products

d. Sampling procedure of raw material from barrels

– Remove the cap from the barrel.

– Remove the cover from the disposable pipette utilizing new pipettes between lots and at the component changeover.

– Apply pipette ball to end not inserted into the sample.

– Insert pipette into solution. Squeeze and release the pipette ball, taking care not to get liquid inside the ball.

– Release liquid from pipette into sample bottle (amber glass).

– Cap bottle securely (metal cap).

– Replace the cap on the barrel.

– Apply the “Sampled by” label or stamp to the barrel where the sample was taken.

e. In-process raw material sampling procedure from the liquid tank

i. Tank Top Sampling Method

– Remove the cover from the tank top.

– Remove the cover from the disposable pipette utilizing new pipettes between lots and at the component changeover.

– Apply pipette ball to end not inserted into the sample.

– Insert pipette into solution. Squeeze and release the pipette ball, taking care not to get liquid inside the ball.

– Release liquid from the pipette into the sample bottle.

– Cap bottle securely (amber glass bottle with metal cap).

– Apply the “Sampled By” label or stamp to the tank where the sample was taken.

ii. Tank Bottom Sampling Method

– Open the valve and flush approximately two (2) gallons of material into an approved container.

– Return material flush to tank top.

– Obtain a sample from valve placed in a sterile bottle.

– Cap bottle securely (amber glass bottle with metal cap).

– Apply the “Sampled By” label or stamp to the tank where the sample was taken.

f. Sampling of raw material from liquid jug

– Remove the cap from the jug.

– Pour the sample into a sample bottle (amber glass bottle).

– Cap sample bottle securely (metal cap).

– Replace the cap on the jug.

– Apply the “Sampled By” label or stamp or jug where the sample was taken.

g. Sampling procedure of tablet or capsule from drum

– Remove the lid from the drum and open the liner.

– Apply clean gloves, changing them before each lot is sampled and at each component changeover.

– Obtain samples from the top, middle, and bottom of the drum with a gloved hand and place them in the appropriate container(s) (plastic bottle with plastic cap).

– Reseal liner.

– Replace the lid on the drum.

– Apply a “Sampled By” label or stamp to the drum where the sample was taken.  In the Compression/Encapsulation area, apply a red dot in place of the “Sampled By” tag or label.

h. Sampling of end-of-run tablets and capsules

The tablet and capsule sample size depends on the batch size and is determined according to ISO 2859 Acceptable Quality Limit (AQL). 

A Sample equivalent to a Level II General Inspection is taken across the batch.

– If the batch size is between 35,000 to 150,000 – the sample size will be 500.

– If the batch size is between 150,000 to 500,000 – the sample size will be 800.

– If the batch size exceeds 500,001, the sample size will be 1,250.

i. Collect equal tablets or capsules from each bucket to form a representative end-of-run sample. 

ii. Calculate the number required from each bucket by dividing the total sample size (500, 800, or 1,250) by the number of buckets required for the job.

iii. Determine the net bucket weight for tablets (for example, 12kg).  The net bucket weight for capsules is (for example, 9kg).

iv. For example, for a lot size of 416,667 tablets, multiply 416,667 by the fill weight to calculate the product’s weight to be produced. 

 This number then needs to be divided by 1,000,000 to convert milligrams to Kilograms.

 Weight of tablets = 416,667 Tabs x 480 mg/Tab ÷ 1,000,000 – 200 kg.

 Now divide the weight of the tablets by the net bucket weight

 No. of buckets = 200kg ÷ 12 kg = 16.7 = 17 buckets.

 The sample size is 800.  Therefore, 800 ÷ 17 = 47 tablets per bucket.

v. Collect the tablets or capsules in a plastic bag. The bag should be labeled with the item number, product name, lot number, date, average weight (as determined during in-process testing), signature, and date and marked “End-of-run.”

vi. The samples are delivered to the Quality Control Laboratory for testing.

i. Sampling of coated tablet and capsule

While the coating pan continually mixes the tablets, a representative sample is taken by transferring small scoops from the coating pan as the tablets are mixed during the coating’s cooling-down process.

– Approximately 100 grams are collected in a labeled plastic bag.

– The plastic bag is labeled with the item number, product name, lot number, date, average weight (as determined during in-process testing), signature, and date, and marked “coated.”      

– The samples are delivered to the Quality Control Laboratory for testing.

j. Liquid sampling of suspensions

– Sampling is accomplished with a ladle that has been previously cleaned.

-The suspension product should be thoroughly mixed before sampling. 

– The sample process is undertaken immediately after cessation of stirring. 

– The operator collects a sample as instructed in the manufacturing instructions.

– Label each sample container with the following information: item code, product name, batch number, sample position, signature, and date.

– Where a sample from the bottom is required, it is taken from the outlet valve at the bottom of the mixing vessel. Approximately 200ml is flushed through the valve before the sample is taken.

– The lid is placed on the sample container immediately after the sampling. The sample is then covered with aluminum foil (as the suspension is light-sensitive) and transferred to the QC Laboratory as soon as possible.

– The sampling tools used should be cleaned immediately after the sampling.

k. Tablet press sampling procedure

– Apply clean gloves before sampling and at each product or lot # change.

– Obtain a sample from the press at the point of exit as it is running.

NOTE:  Never put your hand or any other object in the press while it is running.

l. Deionized water sampling

– Select water port (s) or fixtures and open them to wide-open setting, letting water run to waste for 1-2 minutes.

– Select a sterilized bottle; refer to SOP #_____ for methodology.

– Remove the lid from the sterile bottle and quickly interrupt the stream of water to fill the bottle with at least 150 ML of water.

– Cap the bottle tightly.

– Turn off the relief valve.

m. Sampling of 70% Alcohol

– Collect the following tools for 70% alcohol sampling:

i. 500mL x 5 sterilized jars (for microbiological testing)

ii. 120mL x 1 non- sterilized jar (for chemical testing)

iii. 1 sampling thief – sterilized

iv. 70% Alcohol

v. Latex gloves

vi. Texta for labeling

– Ensure correct gowning procedures are followed for entry into the manufacturing area.

– Ensure latex gloves are sprayed with 70% Alcohol are worn before sampling.

– Label all sample jars with the sample name, batch number, date and time sampled, and the operator name using the labeling marker.

– Spray the drum cap with 70% Alcohol and remove it.

– Remove the sampling thief from the sterilization bag and plunge it into the drum, ensuring the plunger of the sampling thief is down and submerged under the liquid so it fills.

– Gently remove the sampling thief, pull it up, and expel the liquid into the sample jars. Repeat this process until all sample jars are full.

– Tighten the lids of the sample jars to prevent leaking, take the samples to the QC Laboratory, and affix proper labels to the sample jars.

– Send the microbiological samples to the Microbiology Lab for microbiological testing.

n. Packaged product sampling (retain samples)

NOTE:  The quantity and labeling of packaged products are the exceptions to the guidelines under the heading General.

– All samples will be labeled with the product’s finished product label.

– All liquid samples will also be identified with a sample label.

– All work orders are to be sampled at the following rates:

– All solid dosages require one bottle (regardless of count) from the beginning and one bottle from the end of filling.  Verify that enough samples exist to perform adequate tests as needed.

– Liquid filling and packaging work orders require two bottles from the beginning of the filling operation, two bottles from the end, and one retention sample from each work order per lot (a retention sample can be taken from any point).

Re-Sampling procedure

Where a raw material, blend, end-of-run, coated, or bulk requires re-sampling, the sampling steps are the same as those described above for the original sample.

Re-sampling of a material is only permitted under certain circumstances where the integrity of the original sample is doubted, where insufficient original sample is provided to complete the required testing, or for other special circumstances as authorized by the Quality Manager.

For each re-sampling event, a “Request for non-routine sampling” form must be completed.

The form must detail the specifics of the re-sampling event, including the number and size of samples to be taken.

Note where samples will be drawn (original containers or new locations).

Please make sure to know what testing is to be conducted before the samples are delivered to the Quality Control Laboratory for testing.