A-116
Ensuring Identity Purity Strength and Composition of Solid Dosage Finished Products
Original Document
Scanned document (image-only PDF)
Extracted Text
Searchable text extracted from PDF
1.0 Purpose The purpose of this procedure is to describe all stages of manufacturing, packaging, labeling, testing and holding of Solid Dosage Form Finished Products to ensure their identity, purity, strength, and composition. 2.0 Scope This procedure applies to all Solid Dosage Finished Products manufactured at Ion Labs, Inc. 3.0 Responsibility 3.1 It is the responsibility of all departments — Production, R&D, QA, QCS, QCL, Purchasing, Shipping, and Receiving to strictly follow this procedure. 4.0 Definitions 4.1 Identity — A specific unique characteristic of a product; a positive match (complies) between an established/standardized characteristic and a finished product attribute 4.2 Purity — Absence of impurities 4.3 Strength — Concentration of listed component 4.4 Composition — Appropriate list of ingredients and components in finished product 4.5 Quality — Means that the finished product consistently meets the established specifications for identity, purity, strength and composition, and has been manufactured, packaged, labeled, tested, and held under conditions to prevent adulteration 46 QCS-— Quality Control/Systems 4.7. LC- Label Control 4.8 R&D -— Research and Development [SOP Standard Operating Procedure SOP No | Rev Ensuring the Identity, Purity, Strength and A-116 7 | Page 2 of 14 Composition of Solid Dosage Finished Products 4.9 PO — Purchase Order 4.10 CoA — Certificate of Analysis 4.11 RMP — Raw material profile 4.12 RMID — A unique identifying number assigned to each raw material 4.13 R# — A unique identifying number assigned to individual batches of raw materials upon receipt 4.14 RMSTT — Raw Material Specification and Test Ticket - A document that lists test methods, specifications, results and information for each unique raw material 4.15 MBR — Master Batch Record — a compilation of documents and forms that identifies all of the pertinent instructions, process, and specifications necessary to manufacture a product 4.16 BPR — Batch Production Record - an accurate reproduction of the MBR issued to production | 4.17 Product Profile — Establishes a products components, in-process, finished product specifications, and stability which ensure the identity, purity, strength, and composition ofthe product 4.18 FPTT — Finished Product Test Ticket; an internal CoA CCP — Critical Control Point - a point during production of a product at which 4.19 controls are applied and adherence to specification is determined prior to proceeding IAV — Ingredient, Addition, Verification Form- Document containing 4.20 specifications associated with label claim support 4.21 OTC — Over the counter drug product 4.22 RMTS — Raw Material Testing Summary 5.0 References 5.1 A-108, SOP, Good Manufacturing Practices and Personal Hygiene 3.2 B-703, SOP, Solid Coating Pan 5.3 B-704, SOP, Perforated Pan Coating [SOP Standard Operating Procedure SOP No | Rev Ensuring the Identity, Purity, Strength and A-116 7 | Page3 of 14 Composition of Solid Dosage Finished Products 5.4 B-901, SOP, Weighing and Blending Procedure 5.5 B-902, SOP, Compression Procedure 5.6 B-903, SOP, Encapsulation Procedure 5.7 B-904, SOP, Packaging Procedure 5.8 B-905, SOP, Quality Control Inspection Process 5.9 C-103, SOP, Batch Production Record Review and Release of Finished Product 5.10 C-104, SOP, Master Batch Record and Issuance of Batch Production Record 5.11 C-603, SOP, New Product Realization Process 5.12 C-707, SOP, Critical Control Point Specifications 5.13 D-105, SOP, Out of Specification/Out of Trend Investigation 5.14 D-403, SOP, Calculations for Ingredient Addition Verification for Finished Products. 5.15 D-901, SOP, Raw Material Life Cycle 5.16 D-902, SOP, Establishment of Specifications 5.17 E-204, SOP, Receiving Process for Raw Materials 5.18 E-601, SOP, Vendor Qualification 5.19 E-702, SOP, Finished Product Sampling Procedure 5.20 E-703, SOP, Raw Material Sampling Procedure 5.21 E-704, SOP, AQL Statistical Sampling Plan 5.22 E-802, SOP, Quarantine of Materials 5.23 21 CFR Part 111 5.24 21 CFR Part 211 5.25 21 CFR Part 700 [SOP Standard Operating Procedure SOP No | Rev Ensuring the Identity, Purity, Strength and A-116 7 | Page 4 of 14 Composition of Solid Dosage Finished Products 6.0 Procedure 6.1 Purchasing of Raw Materials 6.1.1 All raw materials used in the manufacturing of OTC must be purchased from qualified suppliers, approved by Ion Labs and must be listed on the Approved Vendors List as per SOP E-601 Vendor Qualification. 6.2 Receiving, inspection, sampling, testing, and release of Raw Materials 6.2.1 Receiving of Raw Materials 6.2.1.1 Purchasing will make available in Batchmaster approved POs to warehouse personnel. 6.2.1.2 The warehouse associate compares incoming materials to the packing list and Batchmaster item description. The warehouse will quarantine material that does not match the PO for quality, grade, or vendor. Material will also be quarantined if packaging is damaged. Quality will be notified of the discrepancy and determine the suitability of the material. 6.2.1.3 Warehouse associate assigns a sequential number in the format of R00001 to each incoming raw material, creates a label containing the RMID, raw material name, R number, vendor name, and vendor lot number for the raw material container, and applies to each bulk container of raw material (refer to SOP D-901 Raw Material Life Cycle, SOP E-204 Receiving Process of Raw Materials, and SOP E- 802 Quarantine of Materials). 6.2.2 Inspection and Sampling of Raw Materials 6.2.2.1 QC samples raw materials according to SOP E-703 Sampling of Raw Materials and E-704 AQL Statistical Sampling Plan. 6.22.2 The samples will be delivered to the lab for analysis and logged into the QC laboratory sample log book (Refer to SOP E-703 Sampling of Raw Materials). 6.2.3 Testing and Release of Raw Materials [SOP Standard Operating Procedure SOP No | Rev Ensuring the Identity, Purity, Strength and A-116 7 | Page 5 of 14 Composition of Solid Dosage Finished Products 6.2.3.1 QC Lab completes the testing of raw materials as outlined in the RMP based on the COA Challenge Status, and documents the results on the RMTS (refer to SOP D-901 Raw Material Life Cycle). Note: Data generated for the first component of a partial shipment can be used for the second component release in instances when partial shipments are received, each with the same manufacturer lot # and separate R#s are generated. A separate RMTS will be generated for the second component of the partial shipment for tracking purposes. 6.2.3.1.1 Raw materials that meet the release specifications listed in the RMP can be processed for release. QC lab updates the raw material status in Batchmaster to “Released”. (Refer to SOP D-901 Raw Material Life Cycle and SOP E-802 Quarantine of Materials/ Products). Note: All approved RMs that are used in Ion Labs products are subject to CofA challenges as defined in D-901 Raw Material Life Cycle and must pass verification testing if the RMs are to be used in Ion products. All raw materials require three CoA challenges before reduced testing can be implemented. 6.2.3.1.2 For raw materials that do not meet the release specifications listed in the RMP, the QC lab will update the raw material status in Batchmaster to “Hold” until a final disposition has been made by Quality Management. (Refer to SOP D-105 Out of Specification/ Out of Trend Investigation and SOP E- 802 Quarantine of Materials/Products). 6.3 Production and Process Control System 6.3.1 Master Batch Record and Issuance of Batch Production Record 6.3.1.1 R&D creates Product Profile, prepares the Master Formula, Weighing & Blending Instructions, and supplement facts sheet for each unique formula to ensure uniformity in the finished batch (refer to SOP C-603 New Product Realization Process). [SOP Standard Operating Procedure SOP No | Rev Ensuring the Identity, Purity, Strength and A-116 7 | Page 6 of 14 Composition of Solid Dosage Finished Products 6.3.1.2 The BPR issued to production, accurately follow the appropriate MBR and all steps in the manufacturing of the batch (Refer to SOP C-104 Master Batch Record and Issuance of Batch Production Record). 6.3.2 Manufacturing Operations Note: All manufacturing operation must be conducted under conditions and controls that protect against the potential for growth of microorganisms and the potential for contamination. Only plastic pallets are permitted inside manufacturing areas where raw materials and product are exposed. Wooden pallets are only allowed in packaging rooms when preparing shipping boxes. Wooden pallets are only allowed in the warehouse, hallways and areas where material and product are not exposed. All wooden pallets must be heat-treated and marked “HT”. The personnel must be garbed appropriately with frocks and/or disposable lab coats, shoe covers and/or dedicated shoes as applicable, hair nets, beard covers, safety glasses and gloves (refer to SOP A-108 Good Manufacturing Practices and Personal Hygiene). Identify all processing lines and major equipment used during manufacturing to indicate their contents, including the name of the dietary supplement and the specific batch number. Each stage of the manufacturing process should be approved or rejected by QC personnel. 6.3.2.1 Weighing and Blending Process (Refer to SOP B-901 Weighing and Blending Procedure). 6.3.2.1.1 A QC inspection of the room, equipment, balances, and utensil cleanliness must take place prior to any weighing and blending. The inspection must be documented on the BPR. 6.3.2.1.2 Before weighing a raw material, the following must be verified by the operator and QC inspector and the verification recorded in the BPR: e Check the RMID against the BPR. [SOP Standard Operating Procedure SOP No | Rev Ensuring the Identity, Purity, Strength and A-116 7 | Page 7 of 14 Composition of Solid Dosage Finished Products Check the description of the material against the BPR. Ensure the material has been released by QC. Check the expiration date of the material. 6.3.2.1.3. During the weighing, the following steps should be observed: Tare the scale to read zero between each weighing step. The R # of each raw material must be documented in the BPR. Each step of the weighing process should be checked by a second production person and/or QC inspector as per BPR. 6.3.2.1.4 During the blending, the following steps should be observed: Place the weighed raw materials into the blender, following the instructions on the BPR. Each step of the blending process must be checked by a second production person and/or QC as per BPR. After the blending process QC inspector performs CCP 1 Blending (Absence of Foreign Material and Bulk Density) to ensure blend uniformity, to determine that a product conforms to specifications and make a disposition decision (Refer to SOP C-707 Critical Control Point Specifications). If the blend is approved, QC will release the blend for the next manufacturing stage. If the blend is not approved, Quality and R&D will be notified of the failure. 6.3.2.2 Encapsulation Process (Refer to SOP B-903 Encapsulation Procedure) [SOP Standard Operating Procedure SOP No | Rev Ensuring the Identity, Purity, Strength and A-116 7 | Page 8 of 14 Composition of Solid Dosage Finished Products 6.3.2.2.1 A QC inspection of the room, equipment, balances, and utensil cleanliness must take place prior to any encapsulation. Encapsulation blend has been released by QC and all drums are labeled released/approved. The inspection must be documented onthe BPR. 6:3:2.2.2 Prior to encapsulation, the material ID and description, batch number, and material quantity must be checked against the BPR. Also verify that the blend has been released by QC for further processing (refer to SOP B- 903 Encapsulation Procedure). 6.3.2.2.3 Make all necessary adjustments to be sure capsules meet the current product specifications, specified into BPR: e Capsule Weight e Capsules are completely locked with consistent size, color, and powder quantity e Make sure to use the correct capsule size, color and material specified into BPR. 6.3.2.2.4 QC inspector should perform CCP2 — Encapsulation (Encapsulation Startup Check) to determine that a product conforms to specifications and make a disposition decision (Refer to SOP C-707 Critical Control Point Specifications). 6.3.2.2.5 During the encapsulation, the following steps should be observed: e Every 30 minutes the operator and every hour QC record the in process weight on BPR e In process containers identified with in process label including: e Product Name e Batch Number e Container XX (Number of container) [SOP Standard Operating Procedure SOP No | Rev Ensuring the Identity, Purity, Strength and A-116 7 | Page 9 of 14 Composition of Solid Dosage Finished Products e Weight per Container 6.3.2.2.6 The encapsulation procedures stated in the BPR must be followed. Keep encapsulation equipment adjusted to maintain weight tolerances. G.3.221 After the completion of encapsulation process, capsules must be released and approved by QC personnel. 6.3.2.2.8 If, during the encapsulation process, any problem with the encapsulation machine occurs, stop the machine and immediately notify the department supervisor. 6.3.2.3. Compression Process (Refer to SOP B-902 Compression Procedure) 6.3.2.3.1 A QC inspection of the room, equipment, balances, and utensil cleanliness must take place prior to any compression. Compression blend has been released by QC and all drums are labeled released/approved. The inspection must be documented on the BPR. 6.3.2.3.2 Make all necessary adjustments to the press so that tablets meet the current product specifications, specified into BPR: e Tablet weight e Tablet hardness e Friability and thickness (if required) 6.3.2.3.3 QC inspector should perform CCP2 - Tableting (Compression Startup Check) to determine that a product conforms to specifications and make a disposition decision (Refer to SOP C-707 Critical Control Point Specifications). 6.3.2.3.4 During the compression, the following _ steps should be observed: e Every 30 minutes the operator and every hour QC record the in process weight, hardness, thickness on BPR. [SOP Standard Operating Procedure SOP No | Rev Ensuring the Identity, Purity, Strength and A-116 7 | Page 10 of 14 Composition of Solid Dosage Finished Products e In process containers identified with in process label including: e Product Name e Batch Number e Container XX (Number of container) 6.3.2.3.5 The compression procedures stated in the BPR must be followed. Keep compression equipment adjusted to maintain weight tolerances. 6.3.2.3.6 If, during the compression process, any problem with the tablet press occurs, stop the press and immediately notify the department supervisor. 6.3.2.3.7 After the completion of compression process, tablets must be released and approved by QC personnel. Note: For coated tablets follow SOP B-703 Solid Coating Pan and B-704 Perforated Coating Pan and coating record(s) in the BPR. 6.3.2.4 Packaging Process (Refer to SOP B-904 Packaging Procedure) 6.3.2.4.1 Prior to the beginning of the packaging process, the container(s) containing the tablets/capsules and all packaging components must be inspected by QC personnel for the correct product, batch number, and packaging. They should be released and approved by QC personnel. This has to be documented in the BPR. 6.3.2.4.2 A QC inspection of the packaging area, equipment, utensil and scale(s) must take place prior to the beginning of packaging process. The inspection must be documented on the BPR. 6.3.2.4.3 Tablets, capsules and powder products must pass through the metal detector without indication of containing metals — CCP4 Metal Detection (Tablets, CapsulesandPowders. [SOP Standard Operating Procedure SOP No | Rev Ensuring the Identity, Purity, Strength and A-116 7 | Page 11 of 14 Composition of Solid Dosage Finished Products 6.3.2.4.4 The packaging procedure stated in the BPR must be strictly followed. 6.3.2.4.5 Packaging operator performs four bottle checks at the beginning and every 30 minutes until the end of the packaging process for product quality. 6.3.2.4.6 QC performs four bottle checks at the beginning and every one hour until the end of the packaging process for product quality. Interval based inspections can be adjusted as needed based on risk (refer to SOP B-905 Quality Control Inspection Process). e Verify fill count for tablets/capsules and fill weight for powders. e For Tablets — must be free of chips, breaks, capping, foreign matter and discoloration. Tablets must be consistent in size, color, and shape. e For Capsules — must be free of folding, dimpling, tears. Capsules must be completely locked with consistent size, color, visual powder quantity. e For Powder — must be free of foreign material and consistent in color 6.3.2.4.7. The labels must be issued by LC/QC and must be the correct labels for the job. The product label used must be affixed on the appropriate space(s) in the BPR before the beginning of the labeling process and signed by QC personnel. 6.3.2.4.8 The labeling instructions stated in the BPR must be strictly followed. 6.3.2.4.9 Packaging operator performs four bottle checks at the beginning and every 30 minutes and at the end of the labeling process for product quality. 6.3.2.4.10 A QC Inspector performs four bottle checks at the beginning and hour until the end of the run to ensure product quality. Intervals can be adjusted as needed based [SOP Standard Operating Procedure SOP No | Rev Ensuring the Identity, Purity, Strength and A-116 7 | Page 12 of 14 Composition of Solid Dosage Finished Products on risk (refer to SOP B-905 Quality Control Inspection Process). 6.3.2.4.11 At the completion of packaging, QC inspector should submit to QC Lab reserve samples and stability samples (if required). (Refer to SOP E-702 Finished Product Sampling Procedure). 6.3.2.4.12 The pallet(s) with packaged product/bulk should be properly identified with product name, customer name, batch number, pallet(s) number and quantity. QC will place a "Hold-Pending Release" tag on each pallet and product should be moved to designated area holding for QC test results and release by QC department (Refer to SOP E-802 Quarantine of Materials/ Products). Note: All components and finished products should be held under appropriate conditions of temperature, humidity, and light so that the identity, purity, strength, and composition of the components and dietary supplements are not affected. 6.3.2.5 Finished Product Testing and Release 6.3.2.5.1 QC inspector takes the test samples/micro samples to the laboratory for analysis and logs them in the QC laboratory sample log book. 6.3.2.5.2 QC Lab is responsible for testing all finished products in accordance with SOP D-902 Establishment of Specifications. 6.3.2.5.3. QC Lab performs the specified testing in accordance with applicable laboratory method standard operating procedures and documents in a laboratory notebook or on the appropriate forms (Refer to section D SOPs Laboratory Operations and Specifications). 6.3.2.5.4 At the completion of testing, QC Lab enters the results of the testing on the Method Specific Test Tickets and Finished Product Test Ticket — Internal CofA. [SOP Standard Operating Procedure SOP No | Rev Ensuring the Identity, Purity, Strength and A-116 7 | Page 13 of 14 Composition of Solid Dosage Finished Products 6.3.2.5.5 Any finished product testing failures [i.e. Out of Specification (OOS) results] are investigated per SOP D-105 Out of Specification/Out of Trend Investigation. 6.3.2.5.6 QC should perform the calculations necessary to verify the correct addition of each ingredient to the batch and complete the IAV with the results of these calculations (Refer to SOP D-403 Calculations for Ingredient Addition Verification for Finished Products). 6.3.2.5.7 Completed IAV, completed Method Specific Test Tickets (with reference to any laboratory notebook containing testing performed), completed Finished Product Test Ticket and CofA are collected by QC and included in the executed BPR. 6.3.2.5.8 Quality Systems will review the entire BPR to ensure that it is complete, all required information is entered or attached, and all the signatures/ dates are in place and will make a final disposition (Refer to SOP C-103 Batch Production Record Review and Release of Finished Products). e If the product is released, Quality Systems will notify applicable departments and a warehouse associate will remove the "Hold- Pending Release" tag. e If the product is rejected, QC will change the "Hold- Pending Release" tag to a "QC Hold" tag on a pallet and move the pallet to the designated area until further investigation is performed and finalized. [SOP Standard Operating Procedure SOP No | Rev A-116 7 Ensuring the Identity, Purity, Strength and Page 14 of 14 Composition of Solid Dosage Finished Products 7.0 Revision History Revision Date Description of Changes CCR # By | 05/24/13 New 13-402 V. Iltcheva Combined section 5.3.2.1.4 & 5.3.2.1.5, changed the SOP title in section 5.2.3.1 & 5.2.3.2.1, changed "every 30 min" to 06/18/13 13-464 V. Iltcheva "every | hour" for QA check in section 5.3.2.2.4.1 & 5.3.2.3.4.1, added "thickness" in section 5.3.2.3.4.1 Updated SOP format, changed "QA" to "QC", added Product Profiles in definition section and 6.3.1.1, removed section 5.2.2.1, added note to 6.2.3.2 for partial shipments, added note to 6.2.3.2.1 for C of A challenge, added note for plastic/ wooden 07/25/14 14-0583 V. Iltcheva pallets in 6.3.2, added capsules are completely locked with consistent size, color, and powder quantity in section 6.3.2.2.2, added metal detection for powders in 6.3.2.4.3, changed QC inspection from 30min to 1h Biennial review: added reference to SQF. Removed obsolete 08/24/16 16-0778 K. Burris SOP references. Changed title. Aligned protocol to reflect processes for all solid 12/07/16 16-1116 B. Johns dosage form finished products manufactured at Ion Labs. Update outdated definitions and references, update procedure to 04/14/20 include the use of Batchmaster, edit language for clarity, edit to CC-20-0320 S. Sassman be consistent with current practices. Removed reference to FPSS in definitions and SQF Code in 08/04/21 CC-21-0310 C. Mitchell references. Removed CCP6 from section 6.3.2.4.3.