2. Warren Majerus, VP QA Pharmore Ingredients warren.majerus@pharmore.com
GLUCOSAMINE REVIEW
(How to Avoid Formulation Errors)
Warren Majerus, VP QA Pharmore Ingredients
Kevin Woollard, Dir. QA Pharmore Ingredients

3. GLUCOSAMINE REVIEW Agenda for today: Raw Material Source/processing
New GMP requirements-FSMA CFR part 507
Issues when testing various glucosamine
chemical forms

5. Glucosamine Raw Material Sources
1. CRUSTACEAN SHELLS
Shells are a by product of seafood companies preparing frozen dinners
Shellfish primarily comes from:
Open Ocean Catch of Crustaceans
Farm Raised Crustaceans
2. FERMENTATION(Vegetable Sourced)
Selected microbes grown in nutrient media produce Glucosamine

6. Well Designed Offices

7. Another Corporate Office

8. Properly Stored Raw Materials

9. Which one makes material for you?

10. Properly Constructed Blender

11. Clean and well maintained reactors

12. Picking out the Black Specks Need a preventive program!

13. Product Contamination

14. GLUCOSAMINE REVIEW Agenda for today: Raw Material Source/processing
New GMP requirements-FSMA CFR part 507
Issues when testing various glucosamine
chemical forms

15. Key Points of 21 CFR Part 507-Training p.1
Applies if facility processes, packs or holds animal food
Animal Food Definition: Food for animals which includes raw materials and ingredients
If facility processes both human and animal food, they may choose to comply with Part 117 only
Supplier means the establishment that manuf./processes the animal food (not the distributor or importer)
Preventive Controls Qualified Individual(PCQI) is one that has received training in development and application of risk-based preventive controls
Every facility must have PCQI on staff

16. Key Points of 21 CFR Part 507-GMPS p.2
Hand washing, no jewelry
Plants and grounds clean, free of pest harborages
Pest control, equipment sanitation, clean water supply
Storage conditions that protect product

17. Key Points of 21 CFR Part 507-Food Safety Plan p.3
Must have a:
Written Food Safety Plan that includes
Chemical
Physical
Biological
Preventive Controls that include
Recall plan
Supply chain controls
Sanitation controls

18. Pharmore 6 Step Foreign Supplier Verification
Identify potential manufacturers for dietary ingredient through Nanjing China Office. Manufacturers with 3rd party GMP certificate from NSF, USP, etc. are preferable. 
Request specification, typical Certificate of Analysis, testing capabilities, production capacities and production samples.
Request pictures of production facility with manufacturer to complete self - audit form. As appropriate, Nanjing China Office representative will conduct initial on site audit.
Request myriad of documentation like process flow, allergen statement, residual solvent statement, manufacturer expectation letter, FDA bioterrorism registration number, etc. Including FSMA expected compliance for HACCP program and manufacturer’s raw material Supplier Qualification Program.  
Conduct on site visit by Pharmore USA Auditor.
Purchase ingredient and implement testing program for received lots with ongoing follow up on any corrective actions requested from on-site audit.

19. On-site Auditing

20. GLUCOSAMINE REVIEW Agenda for today: Raw Material Source/processing
New GMP requirements-FSMA CFR part 507
Issues when testing various Glucosamine
chemical forms

21. Glucosamine Content of Different Forms
Glucosamine HCl
Glucosamine Sulfate 2 KCl =100%
HCl=16%
Glucosamine =84%
HCl =16%
=100%
Chlorine=11.7
Glucosamine=59%
Sulfate 2KCl =41%
Glucosamine Sulfate 2 NaCl
Glucosamine=63%
Sulfate 2NaCl= 37%
=100%

22. Mix Several Forms and try to find them??
= how much
Glucosamine?
HCl=16%
Glucosamine =84%
HCl =16
Potassium=41%
Chlorine=11.7
Glucosamine=59%
Glucosamine=63%
Sulfate 2NaCl= 37%

23. Problems when blending different types of Glucosamine in a complex finished product
Tests cannot easily determine if the “Glucosamine” came from the HCl form, the KCl form or the NaCl form.
Only total Glucosamine can be determined, not specific types
Therefore, label claims with multiple forms cannot be verified analytically

24. Label Claim Precautions
Glucosamine HCl is only 84% Glucosamine. If your label states: “Contains 100 mg of Glucosamine,” then your formula must contain 19% more Glucosamine HCl ( 100/.84) to meet label claim. Glucosamine Sulfate 2KCl is only 59% Glucosamine. If your label states: “Contains 100 mg Glucosamine,” then the formula must contain 69% more Glucosamine Sulfate 2 KCl ( 100/.59) to meet label claim. If your label claim names the WHOLE molecule and not just the Glucosamine part, then there is no need for the above additions.

25. Mix Several Forms and try to find them??
= how much
Glucosamine?
HCl=16%
Glucosamine =84%
HCl =16
Potassium=41%
Chlorine=11.7
Glucosamine=59%
Glucosamine=63%
Sulfate 2NaCl= 37%

26. EXAMPLE: When Formulating with Glucosamine HCl to achieve 500 mg of Glucosamine per serving:
Since Glucosamine HCl is only 84% Glucosamine, to make a serving containing 500 mg of Glucosamine requires 595 mg of Glucosamine HCl.
Divide 500/.84 = 595 mg

27. EXAMPLE: When Formulating with Glucosamine Sulfate 2KCl to achieve 500 mg of Glucosamine per serving:
Since Glucosamine Sulfate 2KCl is only 59% Glucosamine, to make a serving containing 500 mg of Glucosamine requires 847 mg of Glucosamine Sulfate 2KCl.
Divide 500/.59 = 847 mg

28. EXAMPLE: When Formulating with Glucosamine Sulfate 2NaCl to achieve 500 mg of Glucosamine per serving:
Since Glucosamine Sulfate 2NaCl is only 63% Glucosamine, to make a serving containing 500 mg of Glucosamine requires 793 mg of Glucosamine Sulfate 2NaCl.
Divide 500/.63 = 793 mg

29. Glucosamine Content
Glucosamine HCl Formula: C6H14NO5*HCl Molecular Weight Total: AMU Molecular Weight of Glucosamine molecule: Molecular Weight of HCl: 36.5 Percent of Glucosamine HCl that is Glucosamine= (180.1/215.64) x 100 = 83.5 % Percent of Glucosamine HCl that is Chlorine= 16.5%

30. Glucosamine Content
Glucosamine Sulfate *2KCl Formula: (C6H14NO5)2SO4*2KCl Molecular Weight Total: AMU Molecular Weight of Glucosamine molecule: (x2) = Molecular weight of Sulfate 2KCl: 245 Molecular weight of 2 KCl: 149 Molecular weight of Glucosamine Sulfate: Percent Glucosamine Sulfate 2KCl that is Glucosamine: (360.2/605.52) x 100 = 59.5 % Percent Glucosamine Sulfate 2KCl that is Glucos Sulfate = 75.4% Percent Glucosamine Sulfate 2KCl that is Potassium= 13.0% Percent Glucosamine Sulfate 2KCl that is Chlorine= 11.7%

31. Glucosamine Content
Glucosamine Sulfate 2NaCl Formula: (C6H14NO5)2SO4*2NaCl Molecular Weight Total: AMU Molecular Weight of Glucosamine Molecule Molecular Weight of Sulfate (SO4) 96.0 Molecular weight of 2NaCl Percent Glucosamine Sulfate 2NaCl that is Glucosamine (360.2/573.3) x100= 62.8% Percent Glucosamine Sulfate2NaCl that is Sulfate (SO4) 16.8% Percent Glucosamine Sulfate 2NaCl that is Sodium= 8.0% Percent Glucosamine Sulfate 2NaCl that is Chlorine= 12.4%

32. QUESTIONS? Warren Majerus, VP QA Pharmore Ingredients
Kevin Woollard, Dir. QA Pharmore Ingredients
PHARMORE INGREDIENTS
RIVERTON , UT
QUESTIONS?