Qualification of Pharmaceutical Working Standards

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Qualification of Pharmaceutical Working Standard
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The certified standard is very much important in pharmaceutical analysis. It ensures that the performed analysis is accurate and assure the safety of drug product. The analysis is always carried out by using the working standard and results are reported against the working standard.

What is Working Standard?

Working standard is defined as, “A drug substance of established quality and purity as shown by comparison to the reference standards.” This working standard is used for routine analysis.

The working standard is qualified against the pharmacopeial reference standard or certified reference standard. Qualification of a working standard is done by using a verified or validated analytical method and its results are compared with the reference standard.

Why to Use Working Standard?

Primary Standard, Reference Standard, or Pharmacopeial Standards is well characterized and certified material by standard regulatory agencies or appropriate laboratories. These reference standards are available with minimum pack quantity at a high cost. Due to the higher cost of the primary reference standard, it is not possible to use this standard for routine analysis. Due to this reason, the working standard is prepared for routine analysis. bearing reference to the original certified reference material.

Selection of Drug Substance:

The working standard must be high purity grade materials. Following is the selection criteria of the drug substance batch for the working standard preparation.

  1. Select the drug substance lot of recently manufactured with adequate validity period i.e. essential retest period or with suitable expiry date.
  2. Availability of drug substance with valid COA and must be comfortably comply the assigned specification.
  3. Analyse 3 different batches of drug substance with verified or validated test procedure.
  4. All three batches must comply as per assigned in-house or pharmacopeial specification.
  5. Select the single batch of drug substance which must be available with sufficient quantity.
  6. Selected batch sample must comply with all test specification comfortably and the assay value close to 100 %. 
  7. Select the batch number for the working standard preparation and collect the sufficient amount of sample quantity for analysis as well as for the use as working standard.  Different vials with minimum quantity which will be sufficient for 1 month. This quantity and number of vials again depend on the requirement of standard per analysis, nature of the drug substance, stability of the drug substance.
  8. Batch selected for working standard preparation must be analysed in triplicate.

Qualification of Working Standard:

  1. Use of primary reference standards for the working standard qualification must have characterisation data with valid COA or valid lot of pharmacopeial reference standard.
  2. Analysis of working standard should be carried out by using calibrated instruments.
  3. The selected drug substance shall be tested as per standard test specifications and standard test procedure of IP/ BP/EP/JP/USP or in-house criteria against the pharmacopeial reference standard or primary reference standards.
  4. Mainly following tests shall be performed for preparation of working standard:
  5. Identification: By HPLC, TLC, IR, UV-VIS Spectrophotometer and Chemical methods,
  6. Loss on drying / Water content,
  7. Related substances: By TLC, GC, HPLC,
  8. Residual solvent analysis by HSGC,
  9. Assay: By HPLC, UV-VIS Spectrophotometer, Chemical methods. The assay performed in triplicate should not be deviate ± 2 % and it should be within specification.
  10. There should not be any deviation, errors or out of specification results at the time of analysis.
  11. If assay is found more than 100 % then consider it as 100 %.

Assign the purity on an as-is basis and also need to check if there is any salt and base correction factor required. Also, it must have clear instructions on vial about use purity on an as-is basis or dry the standard before use with clear temperature condition or depending on the pharmacopeial monograph or as per primary standard test procedure.

After analysis assigns the validity depending upon the nature and stability of drug substance. The validity of the working standard shall be assigned for 1 year or it must be within the retest date or expiry date of drug substance assigned by the manufacturer.

After completion of the analysis and report generated, prepare the COA, and submit for the QA review along with a hard copy or electronic data.

Storage of Working Standard:

After approval of report label the working standards bottles properly with following details:

  1. Name of the compound,
  2. Physical Description,
  3. LOD/water content result,
  4. Assay or Purity on as-is the basis, (Must have clear instruction on vial about Use purity on an as-is basis or Dry before use with clear temperature condition)
  5. Vial number,
  6. Date of preparation,
  7. Validity or Retest date,
  8. Storage Condition.

Store the working standard as per the storage condition of the drug substance. The validity of working standards shall be one year or depend on the nature and stability of the compound. Working standard shall be stored in amber-colored glass bottles with airtight closures. Each vial shall be used for maximum of 2 months or depending on the nature of the standard.

One vial with an adequate quantity of the working standard shall be kept as a “Control sample”.

The working standards shall be revalidated at well-defined intervals to ensure its purity, integrity, and authenticity. Maintain the usage record of the working standard.

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