Using Raw Materials at Risk

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1.0 Purpose 
 
 The purpose of this procedure is to describe the requirements necessary to use a raw material
 
 prior to complete quality release. 
 
 2.0 Scope 
 
 This procedure will be applied to those raw materials that have not completed the required
 
 laboratory testing and have not been released for use. This procedure will define the risk
 categories associated with unreleased raw materials and will define minimal testing required to
 
 be approved for at risk use. 
 
 3.0 Responsibility 
 
 3.1 It is the responsibility of QC Laboratory Management to complete form D-302-F1 RM
 
 High Risk Assessment for Potential Release for Use at Risk for any material intended for
 use at risk in production activities prior to completion of all testing required by normal
 
 release of that material. 
 
 3.2 It is the responsibility of QC Laboratory Management to maintain a High Risk material
 List as outlined in this procedure. 
 
 3.3 It is the responsibility of DC to approve assessments on D-302-F1 RM High Risk
 Assessment for Potential Release for Use at Risk and file this document with RM release
 
 documentation. 
 
 3.4 It is the responsibility of DC to review the release status of all RM used in manufacturing
 processes and ensure that all RM are fully released before releasing any Finished Product
 
 batches. 
 
 
 

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 4.0 Definitions 
 
 4.1 At Risk — state of which using a raw material prior to full laboratory release. Using raw
 materials at risk is further divided into the below risk levels: 
 
 4.1.1 Low — expected to have minimal to no impact for its use prior to full laboratory
 
 release 
 
 Medium —expected to have the potential for finished product impact for its use
 
 prior to full laboratory release 
 
 High — expected to have increased potential for finished product impact for its
 use prior to full laboratory release and generally not recommended to use prior to
 
 full laboratory release 
 
 Prohibited — present the potential for significant impact to the quality of any
 finished product in which it will be used; cannot be used prior to full laboratory
 
 release without the approval of operational and executive management
 
 4.2 Raw Material Classification — based on the form that the raw material is received as
 
 described below. 
 
 4.2.1 Botanical Powder — complete powder form of any plant 
 
 4.2.2 Botanical Extract — created by soaking the botanical in a liquid that is able to
 retrieve certain chemicals or beneficial parts of the plant to be used in a product;
 
 may or may not be received on a carrier ingredient 
 
 4.2.3 Chemical Excipient — inactive material that aides in the processing of a
 
 formulation 
 
 4.2.4 Vitamin or Mineral — active ingredient, natural or synthetic, that are typically
 the main components of any formulation; low percentage vitamins or minerals
 
 may or may not be received on a carrier ingredient 
 
 4.3 DC — Document Control 
 
 4.3 OOS — Out of Specification 
 
 
 

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 4.4 QC — Quality Control 
 
 4.5 R# — Receiving Number; a unique identifying number assigned to raw materials upon
 
 receipt 
 
 4.6 R&D — Research and Development 
 
 4.7 RM — Raw Material 
 
 4.8 COA - Certificate of Analysis 
 
 5.0 References 
 
 Sl C-601, SOP, New Product Approval Process 
 
 D2 D-105, SOP, Out of Specification/Out of Trend Investigation 
 
 a E-601, SOP, Vendor Qualification 
 
 5.4 D-901, SOP, Raw Material Life Cycle and COA Challenge Process 
 
 Sa D-902, SOP, Establishment of Specifications 
 
 5.6 D-302-F1, Form, RM Risk Assessment for Potential Release for Use at Risk
 
 5.7 D-302-F2, Form, Prohibited Risk RM List 
 
 6.0 Raw Material Risk Classification 
 
 6.1 Low Risk raw materials will generally meet these qualifications: 
 
 6.1.1 Raw material supplier is fully analytically qualified, i.e. three lots have been
 
 successfully C of A challenged per D-901 Raw Material Life Cycle and COA
 Challenge Process. 
 6.1.2 Raw material type does not present any significant safety concerns, i.e. microbial
 
 or heavy metal contamination. 
 6.2 Medium Risk raw materials will generally meet these qualifications:
 
 6.2.1 Raw material supplier is fully analytically qualified. 
 
 6.2.2 Raw material is required to meet specific physical characteristics to ensure the
 finished product is able to be successfully processed in manufacturing, i.e. particle
 size, density, form. 
 
 
 

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 6.3 High Risk raw materials will generally meet these qualifications: 
 
 6.3.1 Raw Material has not been fully analytically qualified. 
 
 6.3.2 Raw material has the potential to impact the safety of finished product.
 6.4 Prohibited Risk raw materials will generally meet these qualifications:
 
 6.4.1 Raw materials that have failed to meet all release specification on past receipts
 are Prohibited risk. If a specific root cause was identified for the failure, then it
 
 is possible to consider removal of the material from the Prohibited Risk list, but
 only if the root cause is managed sufficiently to eliminate the failure.
 6.4.2 Raw materials that are inherently unstable are Prohibited risk. Some materials
 
 will degrade or change under transport and/or storage conditions. If these changes
 have the potential to significantly impact the material, then classify that material
 as Prohibited risk. 
 
 6.4.3. Any raw material that is the first time receipt. 
 7.0 Raw Materials Characteristics 
 
 teal Botanical Powders (High Risk) 
 
 7.1.1 Typically not processed to remove contaminants such as heavy metals.
 
 7.1.2 May or may not be treated to reduce microbial contaminates. 
 7.1.3. Critical testing — ID, micro, heavy metals. 
 
 Ta Botanical Extracts (Medium Risk) 
 
 7.2.1 Typically processed to extract components of interests. This extraction process
 may reduce the amounts of potential contaminants that will be present in the
 
 extracted material. 
 
 7.2.2 Extraction process typically reduces the microbial load of the material.
 
 7.2.3 May require strength testing to support a label claim. 
 
 7.2.4 Critical testing — ID, Strength (if applicable). 
 
 7.3 Chemical Excipients (Low Risk) 
 
 7.3.1. Typically synthetically created. 
 
 7.3.2 Potential for contaminants present is significantly reduced. 
 
 
 

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 133 Minimal laboratory testing required for release. 
 
 7.4 Active Ingredients (Low Risk) 
 
 7.4.1 Typically vitamins and/ or minerals. 
 
 7.4.2 Potential for contaminants present is significantly reduced. 
 
 7.4.3 Usually requires strength testing to support a label claim. 
 
 8.0 Procedure 
 
 8.1 Initiate a risk Assessment 
 
 8.1.1 If production operations require access to a raw material before normal laboratory
 
 release testing of that material is completed, initiate form D-302-F1 RM Risk
 Assessment for Potential Release for Use at Risk and complete Phase 1 portion.
 
 The risk questions and assessment process are also summarized in a flow chart
 
 format presented in Attachment 1. 
 
 Decision questions located on Form D-302-F1 RM Risk Assessment for Potential
 
 Release for Use at Risk will determine the requirements necessary for the use of
 any material at risk. 
 
 8.1.4 Proceed to Phase 2 portion of Form D-302-F1 RM Risk Assessment for Potential
 
 Release for Use at Risk. 
 
 $1.5 Phase 1 and Phase 2 must both be completed prior to using any raw material at
 risk. 
 
 Form D-302-F1 RM Risk Assessment for Potential Release for Use at Risk will
 
 be archived with each individual raw material upon completion and release.
 
 8.2 Prohibited Risk Material List 
 
 8.2.1 The QC Laboratory will maintain form D-302-F2 Prohibited Risk Raw Material
 
 List. 
 
 8.252 Assess new raw materials for risk during the specification creation for those
 materials. 
 
 
 

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 8.2.3 Update the Prohibited Risk Raw Material list after OOS results for a material are
 
 confirmed. 
 
 8.2.4 Add Raw Materials identified as Prohibited Risk to form D-302-F2 Prohibited
 
 Risk Raw Material List. 
 
 8.2.5 Sign the form. 
 
 8.2.6 When new raw materials are added to the Prohibited list, DC will replace
 previously approved D-302-F2 Prohibited Risk Raw Material List forms with the
 
 most current form and will publish the form for reference by QC lab Management.
 
 9.0 Revision History 

| Rev | Date | Description of Changes | CCR # | By |
|-----|----------|------------------------|-------|----|
| 0 | 10/06/22 | New procedure. N/A J. Sassman Edited Fl for the following: Changed override requirements to operations management to quality management, added N/A check aa A. Gales boxes where applicable, eliminated signature requirements at the iil aca Shannon bottom of the first page. | - | - |

 10.0 Attachments 
 
 10.1 Attachment | — Flow Chart for At Risk Use Determination 
 
 
 

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 Attachment 1 — Flow Chart for At Risk Use Determination 
 
 Isthe RM used ina ne IsRM 
 Drug Product? i AS for Drug? VvYes 
 
 Isthisa new raw | Isthisa Complete full 
 material? New RM? Ye testing, Do not 
 process at risk, 
 
 Isthis material on 
 IsRM on 
 the HIGH RISK High Risk list?” 
 Material List? 
 ae 
 ——_____¥__. 
 Is thi; s materia,l 
 supplier COA fully | \s Supplier 
 qualified (i.e3. lots COAQualified? 
 fully tested)? 
 No 
 
 IsRM classified as 
 Me ( d se i e u S m O P Ri ) sk nese TM 4Dery Com cr p i l ti e c t al e t r e e s q t u i i n r g ed
 
 Complete paper ID 
 confirmation and 
 Release at Risk 
 
 yo 
 It is permissible to I D s i t e h t e a ry R M I n u g s r e e d d i a en s t a | 4 a a Y I a s D R I M ? Nae Tes C t o i m n p g l a e n t d e a Re le i a D se
 process at Risk (D)) at Risk 
 
 
 

[SOP 

 ION RM Risk Assessment for Potential Release for Use at Risk
 “es Nutritional 
 Labs Form: D-302-F1 CCR No. CC-24-0093 Revision: | 
 
 PHASE 1 
 
 Decision Questions 
 Start with Question 1. Proceed to additional questions as directed by each answer until the answer identifies a
 path forward. Once a path forward has been identified, select N/A for all questions not executed.
 
 O iseYes-— Complete full testing. 
 Q1 —Is RM for drug? Do not release at risk. 
 Is the RM used in a Drug Product? Do not complete additional questions
 CL] No- Go to Q2 
 
 CL] Yes— Complete full testing. 
 Do not release at risk. 
 Q2 — Is this anew RM? 
 Do not complete additional questions
 Is this a new raw material? 
 CL] NoGo t-o Q3 
 CO) N/A 
 L] Yes— Complete required critical testing (define
 Bike savmatenclono Tt n n‘ ie: t: reat list nbeel onwo). sag ms a ca 
 or successfully completed. . 
 Is this raw material classified as High Risk? ONo- ae a additional questions 
 
 LC] N/A 
 LI No— Complete full testing. 
 Q4 — Is this material supplier COA Qualified? Do not release at risk. 
 Is this material supplier COA fully qualified (i.e. 3 lots Do not complete additional questions
 fully tested)? L] Yes— Go to Q5 
 
 CL] N/A 
 CL] Yes— Complete required critical testing (define
 Q5 — Is RM Medium Risk? below). 
 Is the raw material classified as Medium Risk? Release at risk after required testing is
 successfully completed. 
 All other raw materials will default to classification Low | 1 No— Complete paper ID confirmation (C of A
 Risk. review). Release at risk 
 
 LC] N/A 
 Required Testing to release material at risk: 
 
 

[SOP 

 ION RM Risk Assessment for Potential Release for Use at Risk
 QYp Nutstiona Form: D-302-F1 CCR No. CC-24-0093 Revision: 1 
 
 Decision Questions 
 
 Transfer the result from the above questions to one of the options below (select only one).
 
 CL] Complete full testing. Do not release at risk 
 CL) Complete required testing. Do not release at risk until testing completed. 
 
 L] Complete paper ID confirmation. Release at risk. 
 L) Release at risk override with Operations and Quality Management Approval (signatures required below).
 
 Release at Risk Override Approvals OF 5 L] N/A 
 
 Operations Mgmt: 
 
 Quality Mgmt: 
 
 Phase 1 evaluation completed by: 
 
 PHASE 2 — Completion 
 
 C) No testing required, COA reviewed. Raw material approved to be used at risk. 
 
 C] Required testing successfully completed on . Raw material approved to be used at risk.
 (date) 
 
 L] Required testing not successful. Raw material cannot be used at risk. 
 
 CL] N/A (Override approved) 
 
 Completed By: 
 (Author) 
 Approved By: 
 (DC)