SOP FOR PREPARATION AND HANDLING OF WORKING STANDARDS AND PROCUREMENT OF REFERENCE STANDARD

1. OBJECTIVE:

1. To lay down the procedure for preparation and handling of working standards and procurement of reference standards.

2. SCOPE: 

1. This procedure is applicable for preparation and handling of working standards and procurement of reference standards in Quality Control department 

2. This procedure is applicable for the:

1. Procurement and storage of Reference Standards.

2. Usage and destruction of Reference Standards

3. Development and Qualification of Working Standards (WS)

4. Usage and Destruction of Working Standards.

3. RESPONSIBILITY:

1. Quality Control Officer / Executive are responsible to follow procedure as per the procedure mentioned in this SOP. 

2. QC Head is responsible for implementation and compliance of the procedure as per this SOP.

4. ABBREVIATIONS

1. SOP    :    Standard Operating Procedure

2. QC    :    Quality Control

3. NA    :    Not Applicable

4. QA    :    Quality Assurance

5. QCO    :    Quality Control Officer 

6. MSDS    :    Material Safety Data Sheet

7. LOD    :    Loss On Drying

8. COA    :    Certificate of Analysis

5. PROCEDURE: 

Three types of standards are described here:

• Reference Standard

• Working Standard

• Impurity Standard/GC Standards

1. REFERENCE STANDARDS

Qualification criteria for Reference Standards:

1. Reference Standards, for its intended purpose shall be procured from approved source of Pharmacopoeial Commission or through an authorized agent.

2. The QCC / QCO shall ensure that Reference Standard lot shall not be used after the validity date mentioned in the Reference Standard Catalog or 12 months of the date of issue of next lot, if validity is not specified.

3. After receiving the reference standard record the details in the Reference Standard Log Book as per the Annexure-I

4. The certified Standards of non-Pharmacopoeial products, intermediates and impurities can be obtained from Contract supplier. 

5. Each Reference Standards are preserved in a frost-free refrigerator as per storage conditions, recommended in the pharmacopoeia or on label. 

6. The outdated vials of Reference Standards shall be disposed-off and shall be recorded to prevent reuse.

2. WORKING STANDARDS

1. QCO shall maintain a list of working standards used in the laboratory with the validity period, duly approved by the QCM / QAM.

2. Each Working Standard shall have a specific validity period.

3. QCO shall ensure that Specifications containing all Test parameters and STPs, as per the Pharmacopoeial monograph, are available for every Working Standard of Pharmacopoeial product.. Working Standard specifications with critical tests, STPs and corresponding inspection plan shall be available for non-Pharmacopoeial products. 

4. The Working Standard shall be prepared by following manner :

1. The freshly approved batches of RM having high purity and low levels of related substances shall be taken as such for evaluation as working standard. The working standards shell be standardized by two methods if possible.

2. When both Pharmacopoeial method and a Pharmacopoeial reference standard are not available, material shall be standardized; the absolute analytical procedure (titrimetry) provided titrimetric methods are available.

3. The potency shall be defined for the following cases as given below :

1. CASE I  :

Potency (%w/w) =    100 – (Water)

        OR

2. CASE II  :

Potency (%w/w, = 100 – (LOD) 

5. Working standards (If urgency) except GC standards shall be provided by the Contract supplier. A record of receipt shall be maintained and will be considered as reference standard. It should be traceable to reference standard.

6. QC shall ensure that COA contains all test parameters and STPs, as per the In-house approved specification and / or received from the Contract supplier.

3. STANDARDIZATION PROCEDURE

1. The working standards standardized against the working standards given by the contractor shall be standardized as follows:

1. The freshly approved batches of RM having high value of assay or purity shall be taken. The approved raw material of the same contractor shall be considered as a new working standard. All the analytical data shall be as per the raw material analysis data. 

2. There shall be 14 vials for one year, each vial shall have 1 months validity and total validity of the working standard shall be of one year.1 vials are kept for re standardization. other one vials are kept for damages or spillages

For working standards standardized against the reference standards:BY HPLC.

2. Evaluate system suitability and %RSD with the standard solution. The injection sequence shall be as follows:

S.No.        Injection            No. of Injection(s)

1.        Blank            1

3.        Standard 1        Replicate

4.        Sample 1            Single

5.        Sample 2            Single

6.        Sample 3         Single

3. The mean value of the three assay values shall be used as the Potency of the material standardized.

4. When the material is standardized by an absolute analytical technique (Titrimetry), the assay shall be done in triplicate and the mean value shall be used as the Potency of the material standardized.

5. Calculate the potency of working standard from both the area responses of standard. %RSD of all the six values should not be more than 1.0%. The Working Standards for Pharmacopoeial substances, shall be standardized as per the applicable specifications. The acceptance criteria for the triplicate analysis of  assay values shall be as follows:

Test	If Result is	RSD	Diff. (%)
Assay  – By Titrimetry	>80%	NMT 0.2%	--
- By HPLC	>80%	NMT 1.0%	--

All the individual values shall be within specifications.

4. RECORDING AND DOCUMENTATION OF WORKING STANDARD

1. The QCC/QCO shall prepare a Protocol for Qualification of Working Standard as per current version of format no. AKH/WS/001.

2. This shall be approved by Manager-QC/Manager-QA before commencement of the analysis, using a working standard.

3. QCC / QCO shall record results of analysis of the new Working Standard lot in analytical raw data sheet. The COA of working standard shall be prepared as per current version of format no. QC026-F03 The working standard reference no shall be as AKH/WS/001/2016. 001 is first vial of working standard and 2016 is the year of preparation.

4. Analytical raw data of the Working Standards qualification shall be compiled with the test protocols along with the required chromatograms.

5. The entries shall be checked by QCO and signed by Manager-QC.

6. Record of qualification of Working Standard shall be entered in the “record of working standard” as per Annexure-II

7. The analytical records and disposal records shall be maintained with QC as per Annexure-III.

5. VALIDITY PERIOD OF WORKING STANDARD

1. The total period of validity of Working Standard shall not exceed the shelf life/holding time of the product.

2. Expired Working Standards shall be removed from QC and disposed off suitably to prevent reuse. This shall be recorded as per current version of format no. Annexure-IV

6. STORAGE OF WORKING STANDARD

1. Working Standards of the RM shall be packed in appropriate number of screw capped vials duly labeled. The number of vials can be decided based on the production and / or stability schedule.

2. Each vial shall be used for a pre-determined period as recommended by Contract Giver. One extra vial containing the standard shall also be made for usage in case any vial during the work gets damaged.

3. Each vial label shall have the following information:

WORKING STANDARD

Product Name   

Lot No.            :           

Vial No.             :

Assay percentage / Potency    :

Water / LOD            :

Date of preparation        :

Storage             :

4. The Working Standard shall be preserved in its original vial and further packed (amber colored) in tight plastic container/glass container which is labeled, appropriately. 

5. The Working Standards shall be preserved in a frost-free refrigerator at about 2-8°C or  at° recommended storage temperature of products 

6. The log of temperature records shell be maintained.

7. IMPURITY STANDARDS

1. Qualification criteria shall be:

1. All impurities standard shall be provide by Contract Giver or shall be procured from authorized source.

2. Each Impurity Standard shall be preserved in original vials placed in self-locking Poly bags and further packed in tight plastic container, which is labeled 

3. The Impurity Standards shall be preserved in a frost-free refrigerator at about 2-8°C.

4. The storage temperature, if specified, shall be as described on the label of the Impurity Standard.

2. GC Standards

1. Working Standard for GC shall be use from reputed source only (e.g., FLUKA, ALDRICH, MERCK, LANCASTER etc.)

2. COA should be available for each lot of standard.

3. Purity of standard given on the COA and shall be used for calculation of results.

4. GC standards shall be procured as per the labeled conditions or as specified in the MSDS. Validity of 12 months shall be assigned from the date of opening of bottle.