Calculations for Ingredient Addition Verification for Finished Products

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1.0 Purpose 
 
 This procedure describes the process used to calculate the results for the Ingredient Addition
 
 Verification in order to verify the amount of an ingredient declared on the product label which
 
 does not have a scientifically valid test method available to analyze. 
 
 2.0 Scope 
 
 This procedure applies to all raw materials used in dietary supplements, foods, and pet
 supplements that have declared label claims for which a valid analytical method is unavailable.
 
 3.0 Responsibility 
 
 acl It is the responsibility of R&D and QC to determine IAV requirements when drafting a
 new product’s Product Profile, and to include these requirements in the finished product
 
 testing section of the profile. 
 
 3.2 It is the responsibility of R&D to review and approve a product’s IAV template created
 
 by Document Control. 
 
 3.3 It is the responsibility of Document Control to create IAV forms when creating new
 master batch records, as required by the product’s Product Profile. Document Control is
 
 also responsible for ensuring that approved IAV forms are included as part of the
 executed batch record for each product that requires [AV to be performed.
 
 3.4 It is the responsibility of the QC Laboratory to perform the calculations necessary to
 verify the correct addition of each required ingredient to the batch, and to complete the
 
 
 

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 IAV with the results of these calculations. It is also the responsibility of the QC
 Laboratory to check these results and initial and date each value entered, as well as sign
 
 and date the completed IAV and calculation sheet. 
 
 3.5 It is the responsibility of Quality to review, verify, and approve the IAV values and
 calculations, and to sign and date the IAV form. 
 
 4.0 Definitions 
 
 4.1 IAV — Ingredient Addition Verification 
 
 4.2 DC — Document Control 
 
 4.3 R&D — Research and Development 
 
 4.4 BPR — Batch Production Record 
 
 4.5 COA -— Certificate of Analysis 
 
 4.6 QC — Quality Control 
 
 4.7 NLT — Not Less Than 
 
 5.0 References 
 
 5.1 D-401, SOP, New Product Documentation Requirements 
 
 5.2 C-201, SOP, Deviation and Investigation Procedure 
 
 5.3 C-502, SOP, Record Storage, Retention, and Destruction 
 
 5.4 21 CFR 111.75 - What must you do to determine whether specifications are met?
 
 5.5 21 CFR 111 subpart M — Holding and Distributing 
 
 
 

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 6.0 Procedure 
 
 6.1 Products manufactured in-house at Ion Nutritional Labs facilities will be qualified by
 verifying that using a specific set of raw materials evaluated in accordance to the Raw
 
 Material Testing Summary, warehouse controls, a master formula, master batch record,
 manufacturing controls, and quality management systems to ensure that the dietary
 
 supplement product consistently meets the established product specifications. The
 
 warehouse controls are set in place to comply with warehouse or other storage facilities
 holding a dietary supplement as described in subpart M in FDA 21 CFR 111. The
 
 requirements for release are that every finished batch of dietary supplement meets each
 product specification for identity, purity, strength, composition and limits on
 
 contamination that may adulterate a finished product produced at Ion Nutritional Labs
 
 as per 21 CFR 111.75. 
 
 6.2 Calculating Results for the IAV 
 
 6.2.1 Dosage Weight 
 
 6.2.1.1 Tablets 
 
 e The average weight per tablet in grams is calculated from a
 composite of NLT 20 tablets. The average weight calculated from
 
 the QC Laboratory weight variation assessment or a composite
 analysis from the tablet run record can be used. 
 
 6.2.1.2 Capsules 
 
 e The average fill weight per capsule in grams is calculated from a
 composite of NLT 20 capsules. The average fill weight calculated
 
 from the QC Laboratory weight variation assessment minus the
 weight of the empty capsule or a composition analysis of the
 
 
 

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 capsule run record minus the weight of the empty capsule can be
 used. 
 
 6.2.1.3. Powders and Liquids 
 
 e The powder and liquid weights in grams are determined by the
 serving size from the BPR. 
 
 6.2.1.4 Gummies 
 
 e The gummy dosage weight is taken from the average of the deposit
 
 weights as recorded in the Batch Record. 
 
 6.2.2 Total Batch Weight 
 
 6.2.2.1 Tablets, Capsules, Powders, and Liquids 
 
 e The total batch weight is obtained from the weigh and mix order.
 
 6.2.2.2 Gummies 
 
 e Given the nature of gummy manufacturing which involves both
 continuous and batch processes, as well as removing significant
 
 quantities of water from the formula, the total batch weight is not
 used in calculations. However the total batch weight of an
 
 individual active sub-blend is calculated by reviewing the batch
 record. The acid and flavor (added after the sub-blend) is
 
 incorporated in this weight by multiplying the sub-blend weight by
 
 the ratio of combined flow rates to base flow rate. 
 
 6.2.2.3 Dosage Units per batch 
 
 e The total number of dosage units in a batch of tablets, capsules,
 powder servings, and liquid servings is calculated by taking the
 
 
 

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 total batch weight in kilograms, converting to grams, and dividing
 by the average dosage weight in grams. 
 
 e Dosage units per batch are not considered for gummies
 
 6.2.3 Ingredient Weight per Dose 
 
 6.2.3.1 If a raw material with a label claim does not have a validated test
 
 method due to selectivity, sensitivity, sample extraction efficiency or
 other limitation or requirement, IAV can be performed. 
 
 Example 1: Vitamin B12 as Methylcobalamin, using the weigh and
 mix, the actual input of Vitamin B12 is divided by the
 
 actual batch weight then multiplied by 100 to get the
 
 percent composition of Vitamin B12 in the dose. The
 %composition of Vitamin B12 is multiplied by the
 
 average tablet weight in milligrams then multiplied
 again by the % chemical activity (purity) obtained from
 
 the manufacturer or internal CofA on the as-is basis to
 get the mg Vitamin B12 in the dose. 
 
 Example 2: In the case of calcium in calcium carbonate, the
 
 calculation would be similar to Example 1 with the
 difference of the weight of the calcium carbonate would
 
 be adjusted for purity then multiplied by 0.4 (40%) to
 calculate the calcium content (Calctum MW = 40,
 
 Carbonate MW = 60). 
 
 Example 3: In the case of methylcobalamin in a gummy 
 
 formulation. The amount of methylcobalamin added to
 
 one sub-blend would be divided by the total sub-blend
 weight (including acid and flavor) for a % by weight
 
 
 

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 value. That % is then multiplied by the deposit weight,
 then multiplied again by the % chemical activity
 
 (purity) obtained from the manufacturer or internal
 
 CofA on the as-is basis to get the mg Vitamin B12 in
 the dose. 
 
 6.2.3.2 If the serving size is more than one, multiply the amount of the
 ingredient per dosage unit by the serving size to determine the
 
 ingredient weight per serving. 
 
 6.2.4 Proprietary Blends 
 
 6.2.4.1. Proprietary blends are quantified based on the batch record, the inputs
 
 of which are verified through the weigh and mix. IAV is not required.
 
 6.2.4.2 If an assayable analyte is present in a proprietary blend, the analyte
 
 will require testing if a scientifically valid test method is available.
 
 6.2.4.3 Customer requirements supersede any internal IAV requirements.
 
 6.2.5 Calculation Record 
 
 6.2.5.1 A record is prepared for all calculations and results for each raw
 
 material requiring IAV (refer to Attachment 1 — IAV Record and
 Calculations Example). The completed record is attached to the IAV in
 
 the BPR. 
 
 6.2.5.2 If an Excel spreadsheet is used to calculate IAV and the spreadsheet is
 
 not locked and validated, a sample calculation must be performed in a
 
 laboratory notebook to verify the spreadsheet calculation, reviewed,
 and submitted with the approved IAV record. 
 
 6.3 Completion of the IAV 
 
 
 

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 6.3.1 Entering Results 
 
 6.3.1.1 The batch weight of each ingredient requiring IAV is entered in the
 
 appropriate location on the IAV spreadsheet. The calculated amount of
 
 each ingredient is compared to the label claim for that particular
 ingredient or blend, and must be not less than 100% of the label claim
 
 (or customer requested range if applicable) from the approved product
 label or supplement facts. 
 
 6.3.2 Verify and Sign 
 
 6.3.2.1 Each entry is verified. One result in each IAV is verified by manual
 
 calculation to verify the spreadsheet equation if the spreadsheet isn’t
 
 validated. The ingredient units are checked against the units listed on
 the IAV. Each entry is initialed and dated. The form and the
 
 calculation record are signed and dated. 
 
 6.3.3 Final Verification 
 
 6.3.3.1 The completed IAV and the substantiating calculation record are
 reviewed, verified, and approved as part of the completed finished
 
 product test packet by the QC Laboratory. 
 
 6.3.4 If IAV results fall outside of the specified acceptance range, a deviation
 
 investigation should be initiated. Refer to SOP C-201 Deviation and
 
 Investigation Procedure. 
 
 6.3.5 Completed IAV forms are submitted to Document Control as part of the finished
 
 product release packet. Release documents are filed with the executed batch
 records and maintained as per SOP C-502 Record Storage, Retention, and
 
 Destruction. 
 
 
 

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 7.0 Revision History 

| Rev | Date | Description of Changes | CCR # | By |
|-----|----------|------------------------|-------|----|
| 1 | 05/31/13 | _ New procedure. | 13-330 | G. Lanke |
| 2 | 06/16/15 | Added note for IAV as needed for liquid products. | 15-0519 | J. Cobos |
| 3 | 08/27/17 | Add clarification to which ingredients will utilize the [AV method. | 17-0913 | L. Titolo |
| 4 | 07/10/18 | Clarified language surrounding requirements of 21 CFR 111. | 18-0232 | J. Coyle |
| 5 | 01/12/22 | Updated to reflect current practices. CC- Clarified calculations for IAV. Clarified sources of input for IAV | 22-0017 | J. Sassman |
| 6 | 08/01/24 | calculations. Redefined the calculation process for proprietary CC- blends. Expanded requirements for IAV calculations and reporting. | 24-0319 | B. Johns |

 $8.0 Attachments 
 
 8.1 Attachment | — IAV Calculations Example 
 8.2 Attachment 2 — IAV Specification and Results Form Example 
 
 
 

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 Attachment 1 — IAV Calculations Example 
 
 Ingredient Addition verificationspecif cation and Results Record and Calculations Example
 
 Results Formulas for Each ingredient*: ‘Jon Labs Garcinia cambogia Capsules SPOOFED
 oo c es beeeee ea ececescresceteselcesussereestetegissisdhserenatsteisiiaeisietsereanin a ea
 Averageweighs of each capsule from Encapsulation RumRecor: : : : O7500 : of/capsule
 Average fill weight of each capsule equals: 8.7560,efeapoule-copsule weightofa "OT _ Capsule ennn rh 0.63600 ‘gfcapsule.
 Total capsule fill gross weight fron weeiggst awl mix yied cece cc cccscscecevsdececececectctesbevevscscrvevevscseseterss lecscsvevsvivevivsveveviviviviticivitecieeeseseses SRA kgfbatch
 Total Capsules produced iin’ a724 ‘kefbatoh 41000 a/ke = 972,400 = afbatchf 636 efcap = 900,600 capsules/batch
 wngrediomt x: Cakdwn (As Cakium Carbonate} BI. Percent coc mises essr esses ieee ieedoseretsesississeissretisississisitsisisitfessrese
 boven iwoight mgrediont used inthelatchc” 60.81 kg” Xpercantactwe” 0 ML weghto ale ag gia
 Weishtof Calcium per batch: 22.4997 kf Number of capsules: - 900,000= Weipegr cahpsutle: .OORA4S9oGOkTe
 Weight CaM csPercapsule: | 0.0000249996607 Ke X1,000,000 mp/kg =the weightof | OOM Calcium. ‘in each Capsule,
 Bw ng Caliches ‘in cach Capsule X 2 capsules per serving = SOM ing Calcium per serving.
 ingredient 2 Poteau (2s Potarshun Cloride) eee eeeEEEEE SeCeeeeeeeeeeeee S24 Percent aL
 boven |weight ingredient used inthebatsh: = 9A hg Xpencentaciwe «SDA Wego Potassium a Ou Agwich
 Weight of Potassium : per batch: : 22.50056:kg/ Number of capsules: : 90,000: Weight per capsule: 0. 200025000022:ke
 Weight PotashPer capsule: | 0.000025000622 Kg X 1,000,000 me/ke =the weightof FOO ccc PORBSSIBM OO Hitteach Capsule,
 J ng Potassium sn cock Copnute K2 copsnies per serang S000 eng Potasshaen per serving.
 ingredient: Chromium (a5 Chromium faring Acid Choke = Percent voces cehice cece eee cectte eevee viet eeevivevevevevtviveevivivivivevsliveveveveveveveve eee,
 boven iweight mgredient used inthokatch: G3 kg” Xpercentaciwe” Sag ML wWeghtof Gomme ga
 Weishtof Chromium ‘perbatch: 6.00:ke/Numberof capsules: : 900,00=0 Weipegr cahpsutle: S.COCORTLDRERkDg
 Weight1 =0 <nwcoem ium Chromium “ipne recaachp sCualpes:u l_e€ .XG20 0c0a06p10e0s00 0p:e rK es Xe 1rv,in6g 00,020m0o0g0/0,kg 0 =n0tehe0e weighC hromium 18.0pe0r s erving. Chromium -in each Capsule.
 ingrediont & Gariniacombogia Extract 1.0 Percent re a oe ceeeeeeeeeeeeeeees
 boven |weight ingredient used inthebatch: AS kg” Xpercentactiwe 100 = Weightof Garciniacambogiafairect aS Agfwich
 Weightof Garcinia carnmbogia Extract per batch: 450:ke/ Numof bcapesulres: 90,000 :— Weight per capsule: C.COCSOODOD000:ke
 Weight ‘Garcinia cambogia Extract per capsule: _0.600500000000: Kg X 1,000,000 mg/kg =the weight of 500.00 ang: Garcinia cambogia Extract:in each Capsule,
 re SILn mg Garcinaa combogsn Extract cock Copmute K2 capeuien per serving = 1000.00 sy Garcinia combogis Extract per serving. co cssvvesietsrevisietsrivevietesipesiesvetsveteveee
 GenerBay tfeatse ee ce 
 *All calculations generated marvually. 
 
 
 

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 Attachment 2 — Ingredient Addition Verification Specification and Results Form
 Example 
 
 Ingredient Addition Verih cation Spec cation and Results Form {Example} 
 
 Prodact Name Garcia Cambopia Capsules SMPOOOP 10150 
 
 Ingredient Name ac) Specification Speciferation Results Calonatted By/Date
 (95% of LC) (105% of LC) 
 
 Calcaum (as Caicamm Carbonate) 500000 mg 475000 amg 52.5000 mg 
 Potassiom (as Potassium Chiogide) 50.0000 mz 47.5000 me 52.5000 mg