Qvents Template

Excipient Risk Assessment

Excipient Name	Material Code
Excipient Manufacturer	Assessment Document Number
Material Origin (Animal / Vegetable / Mineral / Synthesis /Others

1. Excipient Source Risk Assessment
S.NO	Source risk element	Risk Category (Low / Medium / High)	Rationale
1.	TSE (transmissible spongiform encephalopathy) and BSE (transmissible spongiform encephalopathy) risk
2.	Potential for viral contamination
3.	Potential for microbiological or endotoxin/pyrogen contamination;
4.	Potential for any impurity originating from the raw materials, e.g. aflatoxins or pesticides
5.	Potential for any impurity generated as part of the process and carried over, e.g. residual solvents and catalysts;
6.	Sterility assurance for excipients claimed to be sterile
7.	Potential for any impurities carried over from other processes, in absence of dedicated equipment and/or facilities;
8.	Risk of Nitrosating agents / Nitrosamines from excipient
9.	Stability of excipient;
10.	Risk of storage and transport temperature, cold chain requirements
11.	Supply chain complexity;
12.	Packaging integrity risk, adulteration, manipulation risk
13.	Manufacturer reliability, track record past performance record on quality and /or performance issues

Risk categorization criteria
1.	Contamination Risk TSE/ BSE Low: Not of animal origin, Milk related products like Lactose Medium: Animal origin, but not from bovine / other animals involving animal tissues vulnerable for TSE / BSE impact High: Excipient material of bovine animal /other animal origin involving high-risk tissues, such as the brain and spinal cord
2.	Contamination Risk Viral Safety Low: Non Animal or Human Sources Medium: Animal source material but not involving cell lines/ organs or tissues of human or animal origin, have effective controls to remove or inactivate potential viral contaminants like heat treatment, pasteurization, high or low pH treatment, solvent treatment etc. High: Products derived from invitro culture of cell lines or invivo culture of cell lines or organs or tissues of human or animal origin, products derived from blood or urine or biological fluids of human or animal origin
3.	Potential for Microbiological or Endotoxin / Pyrogen contamination Low: Material is not of Animal or Vegetable origin; Material from Synthetic or Mineral origin with appropriate GMP practices for excipient manufacturing. Material do not provide a nutrient source for microbial growth. Medium: Material is not of Animal or Vegetable origin. Material from Synthetic origin but can be a nutrient source for microbial growth. High: Material of Animal or Vegetable origin, Material provide a nutrient source for microbial growth, High water activity
4.	Potential for carry over of impurities like Aflatoxins, Pesticide residues from raw materials Low: Excipients of mineral or synthetic origin, animal origin High: Excipients of vegetable origin, no risk assessment or controls for aflatoxins, pesticide residues in raw materials
5.	Potential for carry over of impurities from excipient manufacturing process – Residual solvents, Catalysts, Elemental impurities Low: Manufacturing process do not involve solvents, catalysts Medium: Manufacturing process involve solvents and / or catalysts, risk assessment available for process impurity carry over, specification controls in place for potential impurities High: No risk assessment and / or specification control of process impurities
6.	Sterility assurance Low: Excipient is for non-sterile, non-parenteral drug products High: Excipient is for sterile drug products
7.	Potential for carry over impurities from other processes / products Low: Dedicated facility, dedicated equipment for the product Medium: Multiproduct facility, adequate risk assessment, GMP cleaning practices, cleaning validation High: Multi product facility, procedural controls on cleaning, cleaning verification, cleaning validation are poor or absent
8.	Nitrosating agents / Nitrosamines risk Low: Animal origin, Mineral origin with no solvents and reagents with risk of nitrosamines in the process, no process water involved in manufacture. Process use highly purified water with no chloramine or ozone in water treatment Medium: Synthetic origin, process has nitrosation reaction or secondary amines or solvents and reagents which can contribute to amine residues (DMF, NMP, Quaternary ammonium salts like TBAH), potable water used in process and water treatment involving Chloramine, Ozone, Multi product facility with other products having nitrosation reactions, reagents or secondary amines High: Excipient process has nitrosation reaction / reagents and amines / amine contributing reagents in same or different steps
9.	Excipient stability / degradation risk Low: Stable excipient, shelf life and storage conditions are supported by stability data High: Excipient not known to be highly stable, formal stability data or studies are absent
10.	Storage / Transport condition/ Cold Chain risk Low: No specific storage / transport temperature conditions for excipient High: Excipient requiring controlled temperature or cold chain transport
11.	Supply Chain complexity Low: Purchased directly from manufacturer, purchased from region with controls on counterfeiting and security (US, Europe, Canada, Australia), not repackaged by intermediaries, transported from manufacturer through qualified carriers, tamperproof containers Medium: Minimum intermediaries in supply chain but reliable, contracts and agreements in place with intermediaries High: Complex supply chain with several intermediaries, region of security concerns and manipulations, no tamper proof seals
12.	Packaging Integrity risk Low: Low supply chain complexity, tamper proof packing and seal High: High supply chain complexity, poor tamper proof pack, seal integrity
13.	Manufacturer Reliability Low: Established manufacturer with reliable track record, no complaints, no past quality defects or performance rejections (last 3 or more years) Medium: Minimal experience with Manufacturer, minor quality or performance issues in past supplies High: No experience with manufacturer, history of excipient variability, history of quality failures and complaints

2. Drug product matrix for Excipient function risk assessment
Drug Product Attributes						Excipient functional risk in the product
Drug Product	Product Code	Function of the Excipient	Dosage Form	Sterile or Non Sterile	%ge of excipient in Product	Daily Patient Intake of Excipient	Dosage form risk	Daily Intake risk	Functional risk	BA / BE risk	Composition risk	Product CQA risk	Sterility risk

3. Consolidated Excipient function risk assessment
S.NO	Functional risk element	Risk Category* (Low / Medium / High) (Mark highest among all products)	Rationale
1.	Dosage form risk on patient safety due to type of dosage form
2.	Risk due to daily intake of excipient on patient safety
3.	Functional risk due to functionality of the excipient in the drug product / process
4.	Risk due to excipient related factors affecting bioavailability and processability for the drug product
5.	Risk or impact on drug product quality / performance due to change / variability in excipient sources / batches
6.	Risk due to percentage of excipient in the drug product formulation with respect to contamination carry over, product attributes
7.	Risk or impact of excipient on critical quality attributes (CQAs) of the drug product (due to variability, changes in excipient)
8.	Drug product sterility risk due to excipient
9.	Risk of Composite excipients

Excipient function risk categorization criteria
1.	Dosage Form Risk Low: Topical applications and other similar applications Medium: Solid oral dosage forms, liquid oral dosage forms, ingestion route High: Sterile, Injectables, Parenteral preparations, Ophthalmic preparations, Products intended to application on open wounds
2.	Daily Intake Risk Low: Maximum daily dose of excipient does not exceed known maximum dose of the excipient in any drug product, Acceptable Daily Intake (ADI) by JEFCA (Joint FAO/WHO Expert Committee on Food Additives), For Topical products, Cosmetic Ingredient Reviews (CIR) database, USFDA-IID (Inactive Ingredient Database) High: Maximum daily intake exceeds known maximum dose of excipient material
3.	Functional Risk Low: Diluent, Coloring agent, Flavor, Sweetening agent, Emollient, Tonicity agent Medium: Thickener, Coating agent, Former, Compression aid, Lubricant, Glidant, Anticaking agent, Humectant, Suspending / dispersing agent, Buffer, Adhesive, Penetrant, Disintegrant, Binder, Capsule shell, Plasticizers, pH modifiers, Chelating and/ or complexing agents, Antioxidants, Suppository base, Suspending and /or viscosity-increasing agent, Stiffening agent, Propellant High: Antimicrobial preservative, Vehicle, Release modifier, Wetting / solubilizing agent, Process / cleaning water
4.	Function of excipient in the formulation with respect to bioavailability, processability Low: Factors affecting processability, no significant impact on bio availability High: Factors affecting bioavailability
5.	Functional variability and control by specifications Low: Functional attributes or characteristics which affect functionality is well captures in the Excipient specifications and controlled, risk of drug product performance variability is low due to variability in excipient High: Functional attributes of excipient in drug product are not controlled by excipient specifications (Key Functionality attributes: Bioavailability, Dissolution, Disintegration, Modified release)
6.	Proportion of the excipient in the medicinal product composition (impact of contaminants) Low: Proportion <5% Medium: Proportion 5-25% High: Proportion >25%
7.	Potential impact on the CQA (critical quality attributes) of the medicinal product (due to variability, changes in excipients) Low: If there is nil / minimal impact on CQAs High: If there can be an impact on CQAs CQAs: Dissolution, Solubility, Content Uniformity, Impurities, Assay, Stability of Medicinal product
8.	Sterility assurance Low: Excipient is for non-sterile, non parenteral drug products High: Excipient is for sterile drug products
9.	Risk of Composite excipient Low: Excipient is not a composite excipient Medium: Composite or coprocessed excipient, but all components of the composite excipient are from same type of source High: Composite excipient with components from different type of source