Submitting a Monograph

Technical Information Requirements For Monograph Review

Approved April 2014

13. Appendix

Homeopathic Pharmacopoeia Convention of the United States Monograph Review Committee Checklist

Regulatory Reference	Review Sub-Committee	Requirement	Botanical Minimum Requirements	Botanical Best Practices	Zoological Minimum Requirements	Zoologiucal Best Practices	Chemical Minimum Requirements	Chemical Best Practices
		Nomenclature
	Botanical	For Botanical Starting materials: Scientific Name: USDA GRIN Taxonomy name. Family, Genus, species, variety and chemo-type	YES
	Chemistry	For Zoological Starting Materials: USDA Taxonomy name Family Genus, species, variety, tissue, fluid, part of organ, organ			YES
USAN, CAS, USP, EP, HMPWG Guidance on Module 3	Chemistry	For Chemical species: International Nonproprietary Name or compendial name. IUPAC, CAS					YES
		Other Pharmacopoeia Names:		YES		YES		YES
		Other Homeopathic Names:		YES		YES		YES
HMPWG Guidance on Module 3	Botanical	Synonyms: English, Latin, French, German, Spanish, Italian, other		YES		YES		YES
		Structure
FDA CPG UCM070491	Chemistry, Toxicology	Chemical class of the constituent or characteristic marker , if known	If known		If known
FDA CPG UCM070491	Chemistry	Chemical class					YES
	Botanical	Surrogate species within the genus used as an active or marker compound reference		YES		YES		YES
		Structural Formula					YES
	Chemistry	Stereochemistry: including diastereoisomers and enantiomers.					If applicable
	Chemistry	Molecular Formula					YES
	Chemistry	Molecular Weight					YES
FDA CPG UCM070567	Chemistry	Schematic amino acid sequence glycosylation sites or other post-translational modifications and relative molecular weight					If applicable
FDA CPG UCM070567	Chemistry	For peptides, characterization should include data on the amino acid sequence, and when relevant, peptide map. For DNA products, characterization should include nucleic acid sequence, DNA melting point, and side chain modifications when applicable.					YES
FDA CPG UCM070567	Chemistry	Confirmation of the proposed chemical structure based on spectral data (especially 2D NMR and IR) and/or other relevant analytical data.					If applicable
		General properties
Q6A and Q6B	Chemistry	A list should be provided of physicochemical and other relevant properties of the drug substance					YES
FDA GPG UCM070567	Botanical	Country of origin		YES		YES		If applicable
	Botanical	Natural habitat and geographical distribution of the plant, alga, macroscopic fungi, or animal	YES		YES
FDA GPG UCM070567	Botanical	Part of plant, stage of development	YES
HMPWG Guidance on Module 3	Botanical	Botanical material fresh or dry	YES
	Chemistry	Morphological, histological and anatomical description (including gender, if applicable)			YES
HMPWG Guidance on Module 3	Chemistry/Botanical	Current sources of the substance including its geographical location and whether it is cultivated or harvested from the wild		YES		YES		YES
HMPWG Safety of substance of Biological Origin	Chemistry	Age, Health status, method of breeding and feeding of animals, immunisation, techniques (immune sera) with description of antigens, culture media (microbial strains) If applicable			YES
HMPWG Safety of substance of Biological Origin	Chemistry	Conditions of slaughter and dissection of animals If applicable			YES
HMPWG Safety of substance of Biological Origin	Chemistry	Assessment of the risk of infectivity including viral, bacterial and prionic diseases			YES
	Chemistry	For raw materials of viral origin: method of inactivation			YES
	Chemistry	Biological activity
	Administrative	Distribution controls on the starting material imposed by any regulatory authority	YES		YES		YES
FDA GPG UCM070491	Botanical	Environmental assessment
FDA GPG UCM070491	Botanical	The critical habitat of a species that has been determined to be endangered or threatened		YES		YES
FDA GPG UCM070491	Botanical	Is the species endangered or threatened species under the Endangered Species Act or the Convention on International Trade in Endangered Species of Wild Fauna and Flora		YES		YES
FDA GPG UCM070491	Botanical	Is the species entitled to special protection under some other Federal law or international treaty to which the United States is a party		YES		YES
	Toxicology	Safe Handling Practices		YES		YES		YES
		Manufacture
	Manufacturing Quality	For the batches used for clinical submission: The name, address, and responsibility of each manufacturer, including contractors, and each production site or facility.	YES		YES		YES
	Manufacturing Quality	Identification of compendial manufacturing methods used; if noncompendial method, then processes should be explained and described with the same level of detail as the primary process.	YES		YES		YES

Homeopathic Pharmacopoeia Convention of the United States

Regulatory reference	Review Sub-Committee	Requirement	Botanical Minimum Requirements	Botanical Best Practices	Zoological Minimum Requirements	Zoologiucal Best Practices	Chemical Minimum Requirements	Chemical Best Practices
		Control of Materials
FDA GPG UCM070567	Manufacturing Quality	Information on the quality and control of materials used in the manufacture of the drug substance should be provided. Information demonstrating that materials meet standards appropriate for their intended use should be provided, as appropriate.		YES		YES		YES
FDA GPG UCM070491	Botanical	Botanical certificate of authenticity	YES
FDA GPG UCM070491	Botanical	Macroscopic description of the plant/part used against a voucher specimen	YES
FDA GPG UCM070491	Botanical	Macroscopic description of the plant/part used against a voucher specimen	YES
FDA GPG UCM070491	Chemistry, Manf. Quality	Photo of the voucher speciment	YES
HPUS	Botanical	Appearance		YES		YES		YES
FDA GPG UCM070491	Manufacturing Quality	Chromatographic and or Spectrographic fingerprint	YES		If Applicable		If Applicable
FDA GPG UCM070491	Manufacturing Quality	Publicly available quality standards/methods	If available		If available		If available
HMPWG Guidance on Module 3, FDA GPG UCM070491	Chemistry, Manf. Quality	Marker compounds		If Applicable		If Applicable
FDA GPG UCM070491, HMPWG Guidance on Module 3	Chemistry, Manf. Quality	Heavy metals		YES		YES		YES
FDA GPG UCM070491, HMPWG Guidance on Module 3	Chemistry, Manf. Quality	Microbial limits		YES		YES
FDA GPG UCM070491, HMPWG Guidance on Module 3	Chemistry, Manf. Quality	Residual pesticides parent or metabolites		YES		YES
FDA GPG UCM070491, HMPWG Guidance on Module 3	Chemistry, Manf. Quality	Adventitious toxins (e.g. botanicals: aflotoxins)		YES		YES
FDA GPG UCM070491, HMPWG Guidance on Module 3	Chemistry, Manf. Quality	Foreign materials or adulterants	YES		YES		YES
FDA GPG UCM070491	Chemistry, Manf. Quality	Total ash		YES
FDA GPG UCM070491	Chemistry, Manf. Quality	Moisture content	YES			If Applicable	YES
FDA GPG UCM070491		Radioisotope contaminants		If Applicable		If Applicable
	Manufacturing Quality	Quantificative assay chemical or biological	If Applicable		If Applicable		YES
HMPWG Safety of substance of Biological Origin	Manufacturing Quality	Certification of viral security			If Applicable
HMPWG Safety of substance of Biological Origin	Manufacturing Quality	Certification for TSE security			If Applicable
HMPWG Safety of substance of Biological Origin	Manufacturing Quality	Veterinary certificate of wholesomeness			If Applicable
Q2A and Q6B FDA GPG UCM070567	Chemistry	A complete description of analytical procedures and appropriate validation data should be available for any analytical procedures that are not from an FDA recognized standard reference	YES		YES		YES
FDA GPG UCM070491	Chemistry, Manf. Quality	Certificate of analysis	YES		YES		YES
	Manufacturing Quality	Process Validation and/or Evaluation
		Control of Drug Substance
Q2A, Q2B, and Q6B	Chemistry	Validation of Analytical Procedures	YES		YES		YES
Q3A, Q3C, Q5C, Q6A and Q6B FDA GPG UCM070567	Chemistry, Quality, Toxicology	Information on impurities should be provided as applicable. Appropriate limits should be established based on safety considerations and manufacturing experience, stability data.	YES		YES		YES
		Reference Standards or Materials
Q6A and Q6B,FDA GPG UCM070567	Manufacturing Quality	When a national or international reference standard is not available the sponsor’s internal reference material that is reprepsentative of multiple source points may be used as a reference material, against which batches would be tested before their release.		YES		YES		YES
		Stability
		Stability Summary and Conclusions
Q1A, Q1B, and Q5C	Manufacturing Quality	Manufacturer shall demonstrate that the substance remained stable throughout the duration of the clinical studies.	YES		YES		YES
	Manufacturing Quality	Special storage conditions	YES		YES		YES
		Toxicology
	Toxicology	Known Toxic Constituents	YES		YES		YES
FDA CPG UCM079270	Toxicology	Single dose toxicity [Species and route]	YES		YES		YES
S4	Toxicology	Repeat dose toxicity [Species, route, duration]	If applicable		If applicable		If applicable
S2	Toxicology	Genotoxicity	YES		YES		YES
S1, S1A, S1B, S1C	Toxicology	Carcinogenicity	If applicable		If applicable		If applicable
S5	Toxicology	Reproductive and developmental toxicity	If applicable		If applicable		If applicable
	Toxicology	Local tolerance		YES		YES		YES
	Toxicology	Antigenicity	If applicable		If applicable		If applicable
S8	Toxicology	Immunotoxicity	If applicable		If applicable		If applicable
	Toxicology	Dependence		YES		YES		YES
	Toxicology	Metabolites	If applicable		If applicable		If applicable
Q3A, Q3B, Q3C	Toxicology	Impurities	If applicable		If applicable		If applicable