SOP for Control Sample OR Reserve Sample OR Retain Sample Management
1.0 OBJECTIVE:
To lay down the procedure for addressing management of control sample(Reserve sample/retained sample) of finished oral dosage forms (Tablets/Capsules).
2.0 SCOPE:
The scope of this document is to provide procedure for:
Sampling of control samples, storage, movement and retention of control samples, periodic physical verification of the control samples, reconciliation of control samples and disposition/destruction of control samples at [Company Name].
3.0 RESPONSIBILITY:
Quality Assurance (QA) Personnel – Day to day management of Control samples and Control sample area as described in SOP.
IPQA Personnel – To withdraw the Control Samples.
Head QA – To ensure the compliance of this SOP.
4.0 PROCEDURE:
4.1 Part A – Sampling Of Control Sample by IPQA Personnel:
4.1.1 Control samples shall be withdrawn during packaging operation of the product by IPQA personnel for every commercial and submission batch of the product.
4.1.2 The product pack shall be checked for identity of the product, batch number and the packaging style for which the representative sample is to be drawn.
4.1.3 In order to ensure control sample as a representative of complete batch, control samples shall be withdrawn at regular intervals (eg. Start, Middle, & End of packaging operation).
4.1.4 Affix sticker as “Start” (Green Colour), “Middle” (Blue Colour) and “End” (Maroon Colour) on the cartons / blister / strip / bottles accordingly. Specimen samples of the stickers are enclosed in Annexure – I.
4.1.5 In case of bottles the IPQA personnel shall affix the status label directly on the bottles.
4.1.6 Affix the “control sample” label as per Annexure – VIII on each show box / bottle. In case if shrink packaging is done, then the label shall be sticked on shrink pack only.
4.1.7 IPQA personnel shall maintain the records of collection in the “Control sample record” register as per Annexure – II.
4.1.8 Further IPQA personnel shall transfer the Start, Middle and End sample to the concerned QA personnel for storing in control sample area.
Note: After collecting the sample, the same shall be placed in lock and key with identification in packing area until they are sent to the concerned QA personnel in QA department for storing in control sample area.
4.2 Sample Quantity –
4.2.1 For tablets / capsules packed in blister/strip – Sample pack equivalent to at least 300 tablets / capsules shall be retained as “CONTROL SAMPLE” to keep at least twice the quantity necessary to perform all the tests required to determine whether the active ingredient meets its established specifications.
4.2.2 If the finished pack of strips/blisters is more than 300 tablets / capsules, remove the excess quantity by taking out the strips or blisters from the show box.
4.2.3 In no case, the strip or blister shall be cut to ensure 300 tablets / capsules.
4.2.4 In order to get 300 tablets / capsules, if part quantity is to be removed from show box, then the removed strips / blisters shall be handed over to the concerned packing personnel immediately.
4.2.5 In case to get 300 tablets / capsules as control sample, a show box is to have part quantity it shall be corrected by scoring off the actual preprinted quantity and rewrite the actual number of strips / blisters present inside the show box.
4.2.6 The rewriting shall be duly signed by IPQA personnel. Enter the details of quantity withdrawn etc. in the “Control sample record” as per Annexure – II.
4.2.7 If the batch is packed in various pack styles, collect at least one representative unit for each additional pack style. Affix the label as “Representative Sample” as per Annexure – VIII along with the control sample label.
4.2.8 For tablets/capsules packed in bottle – Sample pack equivalent to at least 300 tablets/capsules will be retained as “CONTROL SAMPLE” to keep at least twice the quantity necessary to perform all the tests required to determine whether the active ingredient meets its established specifications.
4.2.9 For large package sizes, where product costs and storage space could be a problem, it is acceptable to retain the samples in a smaller version of the same immediate container closure system in which drug product is marketed or in one that has essentially the same characteristics.
4.2.10 Send the control sample and representative sample if any along with the control sample record to QA department for storing the sample in the control sample storage after completion of batch.
4.3 Part B – Storage, Movement and Retention Of The Control Sample
4.3.1 Storage of control sample:
The concerned QA personnel in QA department shall receive the control sample and check Product Name, Batch No, Mfg. Date, Exp. Date, Pack style and Quantity in “Control sample record” as per Annexure – II against the sample received and verify the integrity of the pack.
4.3.2 Concerned QA personnel will enter the details of control sample received in “Control Sample receipt and physical verification record” (month wise) as per Annexure – III.
4.3.3 Refer the “Location Chart” displayed in the control sample storage room indicating the location of the control samples product wise and place the control sample on the respective shelf rack.
4.3.4 In case there is any change in location or addition of a new product, update the location chart quarterly and destroy the old one.
4.3.5 Control sample shall be stored at Temperature not more than 25°C and ambient Relative Humidity.
4.3.6 Record of Temperature shall be monitored by Temperature Data Logger & by digital thermohygrometer.
4.3.6.1 Temperature monitored by Temperature Data Logger shall be observed monthly. The Temperature data shall be downloaded from the Temperature Data Logger as per the procedure given in the current version of SOP for “Procedure for Locating, Downloading the temperature data, setting and Programming the Temperature Data Logger”. Printouts of the data shall be taken in every first week of the month and shall be reviewed and signed by the concerned QA personnel with remarks (if any) and then sent to QA head for verification.
4.3.6.2 Record of Temperature and Relative Humidity monitored by digital thermohygrometer shall be maintained manually in “Temperature & Relative Humidity record in Control Sample Storage Area” register as per Annexure – lV. Temperature and Relative Humidity recording in the register shall be done once in a day (Working Days) in the morning session for minimum and maximum value of both Temperature and Relative Humidity for the period from when the last reading was taken. Ensure that the Temperature is within the specified limit (NMT 25°C). Relative Humidity is recorded for information only. Clear the reading in thermohygrometer after recording.
Note: Brief deviation from the limit (NMT 25°C) is allowed provided that the results in mean kinetic temperature (MKT) calculated is not more than 25°C; and this allows for excursions up to 30°C variations.
Transient spikes up to 40°C are permitted as long as it does not exceed 24 hours. Mean Kinetic Temperature shall be calculated need based.
The yearly MKT for the preceding twelve months shall be calculated every month using temperature readings (minimum of 104 weekly minimum and maximum readings). Calculation shall be done as per Annexure – IV.
Any time the yearly MKT of a facility approaches 25ºC, the occurrence shall be documented, the cause for such an occurrence shall be investigated and corrective actions should be taken to ensure that the facility is maintained within the established conditions for drug product storage.
4.3.6.3 In case of any abnormality or any excursion in Temperature, inform Engineering Department for rectification.
4.3.7 Movement of the control sample:
If control sample is required to be issued for investigation / reference purpose same shall be issued by the concerned QA personnel on authorization by Head QA / Designee.
4.3.8 If the samples are taken for visual observation/reference purpose only, without disturbing the packing, place them back after completion of observation and record the detail (If sample is moved out from the control sample area) in “Control Sample Movement Register” as per Annexure – V.
4.3.9 Maintain the issuance record in “Control Sample Movement Register” as per Annexure – V. Control sample withdrawn for periodic yearly observation need not be recorded in the control sample movement register as the same is recorded in control sample physical verification record.
4.3.10 Retention of Control Sample
The control sample shall be retained for one year after the expiration date of the drug product and shall be disposed / destroyed within next month after the completion of retention period of the same.
4.4 Part C: Control Sample physical verification (Visual Examination)
4.4.1 Frequency: Once in a year till expiry date of the product.
4.4.2 At the start of every month (first seven working days), check the list of control samples due for observation from the “Control Sample Physical Verification record (Monthwise)” maintained as per Annexure – III.
4.4.3 Take one of the carton/box of control sample of the product for verification. Pull out about all tablets / capsules from one strip / blister (only in case of strip / blister containing less than 20 tablets/capsules) for verification purpose otherwise take only 10 tablets/capsules for verification purpose. In case of bottles, take out about 10 tablets/capsules from a bottle. Re-close the bottle tightly.
4.4.4 Verify the product for the following defect if any under sufficient light:
a. Chipped / broken tablets/capsules, deshaped capsules
b. Integrity of product container, closure system whenever applicable,
blister or strip pack sealing, label intactness etc.
c. Tablets / capsules appearance
d. Black spots on the tablets / capsules
e. Change in color of the tablets / capsules
f. Powder formation in strip / blister [in case of container other than strip/blister, the same shall be recorded in the “Control Sample Physical Verification record(Monthwise)” as per Annexure – III.]
4.4.5 Record the observation made, in the “Control sample physical verification record (Monthwise)” as per Annexure – III.
4.4.6 After verification place the tablets / capsules in double line polyethylene bag and send it for disposal / destruction.
4.4.7 In case of any non-conformity observed during the physical verification of the drug product, immediately inform Head QA. Head QA will investigate in consultation with Head Production and if required will send the sample to QC for analysis. Fill up the nonconformity record by Head QA as per Annexure – Vl and send to R & D, Regulatory Department (if required) and Corporate Quality Assurance for further action.
4.4.8 Periodic observation records for control samples already maintained in the register as per SOP No. SOP/QAD/015/00 will be maintained in the same register till their expiry date as per revised check points and frequency mentioned in this SOP.
4.4.9 Reconciliation of Control Sample:
Quantity removed for physical verification or for any other purpose as mentioned in Control Sample Movement Record (only non-returnable samples) shall be mentioned in the register for “Record of Reconciliation of Control Sample” as per Annexure – IX.
4.5 Part D – Disposition/ Destruction Of Control Samples:
4.5.1 Samples shall be disposed/destroyed as mentioned below:
4.5.2 Strip/ Blister/ Bottle:
4.5.2.1 Remove all strips / blisters / bottles and keep it on one side and leaflets, show boxes, corrugated box and other paper materials on the other side. Defoil the strips / blisters. Remove the tablets / capsules from the blisters / strips / bottles and place them in double line polyethylene bag. Send it to disposal Effluent treatment plant (ETP) with the label as per Annexure – VII with required details in label and put ‘NA’ wherever necessary.
4.5.2.2 Place the defoiled strips / blisters in a double line polyethylene bag. In case of bottle, deface its identity and place them in double line polyethylene bag. Cut all other preprinted packing materials e.g. leaflets, show boxes, cartons etc. into pieces and transfer the same to scrap processing area in double line polyethylene bag duly labeled “For shredding and disposal”.
4.5.3 Record the details of destruction in “Control Sample Physical Verification record” as per Annexure – III and “Record of Reconciliation of Control Sample” as per Annexure –IX.
5.0 ANNEXURE (S):
Annexure I – Specimen Stickers
Annexure II – Control Sample Record
Annexure III – Control Sample Receipt and Periodic Physical Verification Record (Monthwise)
Annexure IV – Temperature and Relative humidity record in control sample storage area
Annexure V – Control Sample Movement Record
Annexure VI – Non Conformity Report (Control Sample)
Annexure VII – Label for “Disposition/ Destruction Of Control Samples”
Annexure VIII – Specimen Label for “Control Sample” and “Representative Sample”
Annexure IX – Record of Reconciliation of Control Sample
Annexure I – Specimen Stickers
START
MIDDLE
END
Product Name:
Product Code: Sr. No.
Date
Batch No.
Mfg. Date
Exp. Date
Packing Style
Collected at / by
Control Sample Quantity
Checked & Received By
Annexure III – Sample Receipt and Periodic Physical Verification Record (Monthwise)
Month:
Date
Product
B. No.
Mfg. Date
Exp. Date
Packing Style
Control Sample Quantity
No. of Tablet / Capsule removed for physical verification
Physical Verification
12 Months
Tablet / Capsules Appearance
Colour of Tablet / Capsule
Black Spot on Tablet / Capsule
Chipped / Broken Tablet / Capsule
Integrity of Product container / closure system
Powder Formation in Strip / blister
24 Months
Tablet / Capsules Appearance
Colour of Tablet / Capsule
Black Spot on Tablet / Capsule
Chipped / Broken Tablet / Capsule
Integrity of Product container / closure system
Powder Formation in Strip / blister
36 Months
Tablet / Capsules Appearance
Colour of Tablet / Capsule
Black Spot on Tablet / Capsule
Chipped / Broken Tablet / Capsule
Integrity of Product container / closure system
Powder Formation in Strip / blister
48 Months
Tablet / Capsules Appearance
Colour of Tablet / Capsule
Black Spot on Tablet / Capsule
Chipped / Broken Tablet / Capsule
Integrity of Product container / closure system
Powder Formation in Strip
To be Destroyed on
Destroyed by / Date
Annexure lV – Temperature And Relative Humidity Record In Control Sample Storage Area
Month :
Thermo Hygrometer ID No.:
Calibrated On :
Next Calibration Due on :
Limit of Temperature : Not more than 25° C
Limit of Relative Humidity : For Record only.
Date
Time
Temperature (°C) Min. and Max.
Relative Humidity (%RH) Min. and Max.
Checked By
Remark
Annexure V Control Sample Movement Record
Product Name
Batch No.
Control Sample Required For (Reason)
Authorised by Head QA / Date
Quantity of sample issued
Issued by / Date
Control Sample
Received Back
Remark (if any)
Quantity
Received by / Date
Annexure Vl Non Conformity Report (Control Sample) .
To,
R&D / CQD / Regulatory Department
From : Site Quality Assurance
Sub: Non conformity report (Control Sample Observation)
Name of Product:
Product Code:
Batch No.:
Mfg. Date:
Exp. Date:
Details of Observation:
Investigation Details:
Head Production
Head QA
Annexure VII – Label for Disposition/ Destruction of Control Samples
Material for Disposal in ETP
Area
Quantity (in Kg)
Sign/Date
Annexure VIII – Specimen Label for “Control Sample” and “Representative Sample”
Control Sample
Qty :
Dt. :
Representative Sample