Standardized Botanical Raw Materials

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1.0 Purpose 
 
 The purpose of this SOP is to define guidelines for setting limits on allowable variation of
 standardized chemicals in botanical extracts. 
 
 2.0 Scope 
 
 This SOP applies to all standardized botanical extracts with single or multi-chemical
 component standardizations. The guidelines also apply to digests of botanical subcomponents.
 These guidelines do not apply to fine chemicals or whole botanicals. These guidelines do not
 
 apply to quantitation of trace toxins or chemicals that only have an upper limit.
 
 3.0 Responsibility 
 
 Sal It is the responsibility of QC Laboratory Chemists to follow these guidelines for raw
 material release. 
 
 3.2 It is the responsibility of R&D to formulate for label claims using these guidelines.
 
 3.3 It is the responsibility of QC Laboratory Management and R&D to set acceptable
 
 variability for a standardized botanical extract and to ensure this procedure is being
 followed. 
 
 3.4 It is the responsibility of the QC Laboratory Management to keep SOP up to date with
 current practices. 
 
 4.0 Definitions 
 
 4.] USP — United States Pharmacopeia 
 
 4.2 QC — Quality Control 
 
 4.3 R&D — Research and Development 
 
 44 RMTT — Raw Material Test Ticket 
 
 4.5 CofA — Certificate of Analysis 
 
 
 

[SOP 

 Standard Operating Procedure SOPNo | Rev 
 Standardized Botanical Raw Materials D-301 I Page gars 
 
 4.6 HPLC — High Performance Liquid Chromatography 
 
 4.7 RSD — Relative Standard Deviation 
 
 5.0 References 
 
 None 
 
 6.0 Procedure 
 
 6.1 General Guidelines 
 
 6.1.1 When an allowed variation is set for the strength metric of a standardized
 botanical extract the activity factor listed in the raw material database will be
 adjusted to the maximum allowed variation for raw material release.
 
 Example: Strength standardized to 50% Component A 
 
 Allowed variability= +/- 10% or 0.1 
 
 Activity = 1—0.1=0.9 
 
 6.1.2 When R&D is formulating for a strength label claim for a standardized botanical
 extract the adjusted activity factor will be used. 
 
 6.1.3. When R&D is formulating with a standardized botanical extract and no label
 claim is made the activity factor used in the formulation is 1.
 
 6.1.4 For QC Laboratory raw material release, the specified variation of a
 standardized material will be listed on the RMTT for the material. The allowed
 variability will be in the format: Strength claim +/- X%. 
 
 6.1.5 The QC laboratory can calculate the acceptable upper and lower thresholds as
 follows: 
 
 Example: Strength standardized to 50% Component A 
 
 Allowed variability- +/- 10% 
 
 Low threshold of activity = 0.5 * (1 — 0.1) =0.45 = 45%
 
 Upper threshold of activity = 0.5 * (1 + 0.1) = 0.55 = 55%
 
 6.1.5.1 | Being within the upper threshold is not a requirement for raw
 material release unless an upper limit is specified by the raw material
 
 
 

[SOP 

 Standard Operating Procedure SOP No Rev 
 Standardized Botanical Raw Materials D-301 1 Page 3 of 3 
 
 manufacturer or requested by the customer. The upper limit cannot
 exceed 100% purity + the %RSD of the assay. 
 
 6.2 Single Chemical Standardization 
 
 6.2.1 For single chemical strength claims in a botanical extract the maximum
 variability allowed is 20% for claims < 5% and 10% for claims > 5%.
 
 6.2.2 Maximum variability allowed when the raw material is standardized by the
 
 manufacturer using titration and the CofA challenge determination using HPLC
 is 25% for claims < 5%, 15% for claims > 5% but < 50%, and 10% for claims >
 50%. This should be used as a rule of thumb. Raw materials may be more potent
 from the vendor and should be examined to determine if the values listed above
 are appropriate. 
 
 6.2.3 Deviations from these variations are permitted with documented justification.
 
 6.3 Multi-chemical / Chemical Class Standardization 
 
 6.3.1 For multiple-chemical strength claims in a botanical extract that use separate
 standards the maximum variability allowed is for each determination is 20% for
 claims < 5% and 10% for claims > 5%. 
 
 63a. For strength claims that apply to a class of chemicals (i.e. alkaloids,
 
 polyphenols, etc.) and the quantitation is a summation of individual chemicals
 using a single chemical reference standard, the maximum variability allowed is
 25% for claims < 5% and 15% for claims > 5%. This should be used as arule of
 thumb. Raw materials may be more potent from the vendor and should be
 examined to determine if the values listed above are appropriate.
 
 7.4 The allowed ranges for single and multi-chemical standardizations are the maximum
 
 recommended ranges to use without justification. Many factors may be considered in
 selecting a range of variability, including quality of the standards, type of assay used,
 and impact assessment on fill weight or tablet weight. 
 
 7.0 Revision History 

| Rev | Date | Description of Changes | CCR # | By |
|-----|----------|------------------------|-------|----|
| 0 | 08/03/15 | New 15-0695 B. Johns | - | - |
| 1 | 04/08/19 | Scheduled review: Added explanations to the standardization specs | 19-0237 | J. Maignan |