Qvents Templates

Excipient Risk Assessment for GMP Elements

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

1. Fundamental GMP elements applicable for all excipient suppliers and manufacturers
S.No	Element of GMP	Rationale / Reference	Adequacy of GMP controls* (A/IA/NA/ANF)	Rationale	Further Risk Assessment & Profile
1.	Establishment and implementation of an effective pharmaceutical quality system;	Fundamental
2.	Sufficient competent and appropriately qualified personnel;	Fundamental
3.	Defined job descriptions for managerial and supervisory staff responsible for manufacturing and quality activities;	Fundamental
4.	Training programmes for all staff involved in manufacturing and quality activities;	Fundamental
5.	Training programmes related to health, hygiene and clothing as identified as necessary to the intended operations;	Fundamental
6.	Provision and maintenance of premises and equipment appropriate to the intended operations;	Fundamental
7.	Documentation system(s) covering all processes and specifications for the various manufacturing and quality operations;	Fundamental
8.	Systems for coding and identifying starting materials, intermediates and excipients to allow full traceability;	Fundamental
9.	Qualification program of suppliers;	Fundamental
10.	System for quality control of the excipient and a responsible person independent from production to release the batches;	Fundamental
11.	Retention of records for incoming materials and excipients and retention of samples of excipients for the periods required by EudraLex Volume 4, Part II;	Fundamental
12.	Systems to ensure that any activity contracted out is subject to a written contract;	Fundamental
13.	Maintenance of an effective system whereby complaints are reviewed, and excipients may be recalled;	Fundamental
14.	Change management and deviation management system;	Fundamental
15.	Self-inspection program;	Fundamental
16.	Environmental control and storage conditions.	Fundamental

2. Additional GMP elements based on excipient risk profile
S.No	Element of GMP	Level of Significance	Significance Rating (High / Low)	Adequacy of GMP controls (A/IA/NA/ANF)	Rationale	Further Risk Assessment & Profile
1.	Controls for TSE and BSE risk	High if TSE /BSE risk is Medium / High
2.	Viral Safety Data Sheet / Validation of Viral inactivation or removal procedures	High Viral safety risk is Medium / High
3.	Microbial Specification and control on Excipients, Control measures to bring down bioburden load, endotoxins, pyrogens	High if Microbial / Endotoxins risk is Medium / High
4.	Control of Aflatoxins, Pesticide residues in Raw Materials	High if aflatoxins, pesticide residues risk is High
5.	Risk assessment for process impurities, residual solvents, elemental impurities, Specification controls for impurities	High if process impurities risk is Medium / High
6.	Sterile facility controls, Facility design, HVAC systems, process controls, operator controls	High if excipient need to be sterile
7.	Cleaning procedures, cleaning verification, validation	High if risk of carry over impurities from other processes / products is Medium / High
8.	Nitrosamine risk assessment / Nitrosamine controls / risk of nitrosating agents / amine residues	High if risk of Nitrosamines / Nitrosating reagents is Medium / High
9.	Stability Data / Formal Stability programme	High if stability risk is high for excipient
10.	Control of storage / transport conditions temperature, cold chain	High if storage / transport temperature risk is high for excipient
11.	Tamper proof seals, Package Integrity controls	Fundamental & Also High if package integrity risk is High
12.	Manufacturer performance tracking, rating, quality / technical agreements	High if manufacturer reliability risk is Medium / High
13.	Acceptable Daily Intake / Tolerable Daily Intake data from reliable sources	Fundamental & also High if daily intake risk is High
14.	Specification controls, defined validated test methods	High where functional risk is Medium / High or where risk of impact on drug product CQA is Medium / High
15.	Process validation, Product quality trends review	High where functional risk is Medium / High or excipient variability impact on drug product is Medium / High
16.	Systems to inform customers of changes, critical events, deviations	High where excipient variability impact on drug product is Medium / High
17.	Contamination control systems (raw materials, environment, process equipment, human interventions)	High where impact of contamination is Medium / High due to excipient composition in drug product
18.	Composite excipient, complete traceability of source of each component	High if the composite excipient risk is Medium or High
*Adequacy of GMP controls (A/IA/NA/ANF): A – Adequate; IA – Inadequate; NA – Not applicable; ANF – Additional Information required

3. Excipient Control Strategy
S.No	Strategy	Strategy Selection Guides #	Control Strategies - Conclusion
	Acceptance based on COA and documentation support	If excipient impact on drug product CQAs, functional attributes, BA / BE risk are low, composition risk, daily intake risk is low
	Acceptance testing – Every Lot	If impact on CQAs is High, composition risk is high, variability risk is high, Manufacturer reliability risk is High If excipient impact on drug product CQAs, functional attributes, BA / BE risk, composition risk, daily intake risk, excipient variability risk, manufacturer reliability risk is High (for all or some of them)
	Acceptance testing – Periodic / Skip testing	If excipient impact on drug product CQAs, functional attributes, BA / BE risk, composition risk, daily intake risk, excipient variability risk, manufacturer reliability risk is Medium to Low, and not High for any of these
	Microbial testing	If Viral safety risk, Microbial / Endotoxin contamination risk is High to Medium
	Prequalification audit	If excipient variability risk, impact on CQAs, composition risk, Manufacturer reliability risk is High. Sterility risk is High. No GMP Certifications are available,
	Prequalification audit and routine audits.	Sterility risk is high
	Unacceptable	Risk is High with respect to several components with respect to Source, Functionality, Manufacturer reliability and there is no reliable GMP certificate
# - The list is indicative