SOP on Preparation of Placebo in Pharma
PURPOSE: To provide guidelines for the preparation of a placebo in a pharmaceutical company.
SCOPE: This procedure is applicable for the preparation of a placebo in a pharmaceutical company.
Attachments
Placebo Preparation Log
Placebo Details
Placebo preparation Record
RESPONSIBILITY :
QC department person : For the preparation of the placebo and To maintain & store the prepared placebo.
Quality control manager: To check all entries in BOM and To ensure the implementation of the defined system.
Quality Assurance Person: To issue BOM of the product.
Production person: To support in preparation of the placebo.
QA head: To ensure implementation of the defined system.
Definitions
Placebo: A medically inactive substance prepared using the same procedure & ingredients except active pharmaceutical ingredients or contains substances which may affect or interfere in ascertaining the actual results during analysis. Placebos are widely used in the determination of impurities, related substances or degradation products in pharmaceutical dosage form. Placebo is also used to determine the specificity during analytical method validation.
PROCEDURE :
SIGNIFICANCE AND USES:
Pharmacopoeial requirements state “peak identified due to the counter ion &/ or other excipients including preservative in the substances under examination may also be excluded.”
Therefore placebo shall be used in case of the following conditions-
(a) Determination of Related substances or impurity testing or decomposition product of pharmaceutical product.
(b) To determine the Specificity of an analytical method.
METHOD OF PLACEBO PREPARATION:
QC chemist shall ask the QA person to issue a copy BOM of the product for which placebo is to prepare.
QA person shall issue a copy of BOM to the QC person.
QC person shall calculate the quantity of materials required in unit dose i.e. mg/tablet, mg/gm for powders or semisolid preparation, mg/ml for liquids of each ingredient required in placebo preparation as per BOM except API or any ingredient/s excluded in placebo.
Now calculate the quantity of raw materials required by multiplying the no. of units with the ingredient in the unit dose for which placebo is to be prepare.
Prepare the record of the placebo.
Assign nine digit unique identification no. to each record using AA/PC-NNN/YY
Where:
AA: product code (use running product codes used at the site)
PC: indicates Placebo
NNN: Serial number of the year (shall start form 001 for new calendar year)
YY: indicate the year ( for year use the last two digits i.e. 24 for 2024, 25 for 2025 & so on).
The batch numbering system of placebo is defined under point 7.3.1 for routine batches & under point 7.3.2 for trial batches.
The production person shall verify all calculations of materials & quantities. If the production person is not involved in placebo preparation QC manager or his designee shall verify the calculation & material quantities. Verified calculations may be preserved & can be used as a reference for future placebo preparation.
Raise the request to issue the material from stores & verify the quantities before using the materials.
The placebo shall be prepared in the quality control laboratory. Call the production person to help in the preparation of the placebo. For development batches concerned person shall provide the placebo who is heading the project.
Use cleaned utensils & glassware for preparation of the placebo to avoid any contamination.
Prepare placebo using the same methodology and addition sequence, particularly for semisolid & liquid preparations as used to manufacture commercial batches of the product.
Preferably keep prepared placebo using container & closure system used for Pharmaceuti-cal preparations.
In case of powder preparation ( placebo of hard gelatin capsules, tablets, granules / oral powder, etc.) store material in poly bags & finally keep it in a tightly closed container to protect it from air & humidity.
Store the placebo under the condition mentioned on the product for which the placebo is prepared.
Use these placebos for the specified times. In case of stability &the placebo shall be kept in simulated conditions used to produce stability.
Prepare a fresh placebo, The holding time expires.
– If the source of major excipients changed which is used in manufacturing of batch of the product.
– In case there is any sign of discoloration, moisture gain, or degradation.
– In case of exposure to adverse environmental conditions or contamination.
– In case of change in formulation & change in manufacturing procedure which may have an impact on analysis.
Records of placebo preparation shall be kept as per details mentioned
The label on each container shall be affixed & bear all relevant details.
BATCH NUMBERING SYSTEM:
In routine analysis, Batch No. of Placebo should be according to AA/XXX/MM/YY.
‘AA’ is the Product code, XXX is a serial number, MM is the month, i.e. 04 for April, and YY is the year. i.e. 24 for 2024.
For trail batch analysis, Batch No. of Placebo should be according to PP/XXX/MM/YY.
‘PP’ is the Plant code, XXX is a serial number, MM is the month, i.e. 04 for April, and YY is the year. i.e. 24 for 2024.
