21-CMO_Supplier_Audit_Questionnaire.pdf

It is the purpose of this questionnaire to facilitate National Institutes of Health (NIH) in gathering information for the approval of your materials/products/services. All information provided in this questionnaire will be treated strictly confidential. In case of any question or comment concerning this questionnaire please contact:

Name: TBD Email: TBD Tel: TBD

This questionnaire may be completed electronically (preferred) or hand written.

Please return the completed questionnaire to the person listed above along with all additional, applicable information/documentation.

Company Name

Name (printed) Signature (Quality Unit person responsible for completing this questionnaire)

Title Location Date

Attachment 21

COMPANY INFORMATION:

Date Form Completed:

Type of product(s) subject to this audit (please check all that apply):

Drug Substance API Excipient Packaging Component Intermediate Drug Product Name of Product(s) Subject to this audit (include dosage forms/services if applicable):

Company Name:

Company Corporate Address:

Company Internet Address:

Key Personnel:

a) Contact Person Name:

Position/Title:

Telephone Number:

Cellular/Mobile Number:

Facsimile Number:

Email Address:

b) Person Responsible for Manufacturing/Production Name:

Position/Title:

Qualifications:

Experience:

c) Persons Responsible for Quality (QA/QC) Name:

Position/Title:

Qualifications:

Experience:

Does your company have a U.S. Agent or U.S.-based Corporate Office that may operate in the U.S. on your company’s behalf? Yes No N/A If applicable, please provide the contact information of US Agent:

Company Name:

Contact Person Name:

Position/Title:

Address:

Telephone Number:

Facsimile Number:

Email Address:

What is the native language at this facility?

If not English, what is the level of English understanding of the contact person (s) named above?

None Little Intermediate Fluent Will English translated documents be available for review? Yes No N/A Does your company manufacture products under cGMPs? Yes No N/A Can you provide a cGMP certification (please attached)? Yes No Can you provide a Debarment certification (please attached)? Yes No Is your company ISO certified? Yes No N/A If yes, please list type of ISO Certification:

Is the company licensed or certified under any other GMP/Quality Scheme? Yes No If yes, please provide brief details):

What is your FDA establishment number (if applicable):

PRODUCT INFORMATION

GENERAL

Do you have a DMF (US) or EDMF (EU) filed for this product? Yes No Please provide DMF #: and Country:

Date the DMF was filed/last updated:

Has this DMF been reviewed by the FDA? Yes No N/A If there is no DMF on file, does your company plan on filing a DMF in the future? Yes No If yes, provide date of planned filing:

What is the batch size for development batches?

What is the price for developmental quantities?

What is the batch size for commercial batches?

What is the capacity per year?

Is there additional capacity planned? Yes No INTELLECTUAL PROPERTY (if not applicable, check box and skip this section) N/A Will you be handling the customs clearance? (if applicable) Yes No N/A Is the material covered under any patents? Yes No Patent number: Expiration Date: Type of Patent:

Will you provide a non infringement statement? Yes No Has this statement been attached Yes No Do you have any patents on your synthesis process? Yes No N/A

RAW MATERIAL INFORMATION

PHYSICAL CHARACTERISTICS

For Raw Materials please provide the following:

Established Name:

Trade Name (if applicable):

Have any enantiomers, hydrates, polymorphic forms, etc. of the material been identified? Yes No If so, how many forms are known? or N/A Which form is your firm manufacturing? or N/A Do you have the capability to micronize the material? Yes No

Do you have a particle size specification?

What instrument is used to determine particle size?

Is the product derived from animal origin (e.g., bovine)? Yes No N/A

Can you provide a TSE/BSE –FREE statement? Yes No If yes, please attach.

Is the product derived from vegetable origin? Yes No

Can you provide a statement that the product is Melamine-Free?

Yes No If yes, please attach.

Can you provide a GMO (Genetically Modified Organisms) - FREE statement?

Yes No If yes, please attach.

IMPURITIES (if not applicable, check box and skip this section) N/A Will impurities be supplied by your company? Yes No Will there be a charge for the impurities? Yes No Are the impurities standards available commercially (i.e., USP, EP, etc)? Yes No Are the impurities within established ICH (QA3) guidelines? Yes No INTERMEDIATES (if not applicable, check box and skip this section) N/A Is there any DMF filed for intermediates? Yes No If yes, please provide DMF #:

If no, does your company plan on filing a DMF? Yes No Provide date of planned filing:

Will the supplier of the intermediate issue a DMF access letter? Yes No Who is the supplier of key intermediates?

Intermediate Name: Supplier Name:

Intermediate Name: Supplier Name:

Intermediate Name: Supplier Name:

Intermediate Name: Supplier Name:

Has the supplier of key intermediates been audited? Yes No Do you have a supply agreement with the supplier of the key intermediates? Yes No Have you assessed the supplier of the key intermediates capacity? Yes No Do you have a back-up supplier for the key intermediates? Yes No

RELEASE AND FINISHED PRODUCT

Are analytical methods for assay, residual solvents and related substances available?

Yes No N/A Are the all the methods validated? Yes No Comments:

Will you supply the method validation reports for these methods? Yes No Do you comply with USP <467> requirements and testing (i.e., ICH) for residual solvents? Yes No Is there an established specification for the material? Yes No Is there a monograph for this material (USP/NF, JP, or EU)? Yes No If yes, provide monograph name:

Does the material meet all criteria listed in the monograph? Yes No If the material is not in USP/NF/EU, will you commit to meet the monograph if it is added? Yes No Are there special handling precautions or safety issues with this material? Yes No

FACILITY INFORMATION

Physical address where manufacturing occurs (where audit will be held):

Number of Buildings located at this site: Size of Site:

List the function, age and construction materials of each of building at the site: (ensure that manufacturing, warehouse, laboratories and administration are included below)

Function: Age: Construction materials: Square footage:

Function: Age: Construction materials: Square footage:

Function: Age: Construction materials: Square footage:

Function: Age: Construction materials: Square footage:

Function: Age: Construction materials: Square footage:

Function: Age: Construction materials: Square footage:

Function: Age: Construction materials: Square footage:

Location: Industrial Park Urban Suburban Rural Approximate number of employees:

Labor Ratio of Supervisors to Production Personnel:

Are the employees regularly trained and is the training documented? Yes No Does each department/unit have Standard Operating Procedures (SOPs)? Yes No Work Schedule:

Hours: Number Shifts: Days Per Week:

Has the FDA or other regulatory health authority inspected your facility? Yes No Has the facility been audited by any other pharmaceutical company? Yes No If yes, provide the date of last inspection:

Enclosure of last inspection report has been enclosed? Yes No Would you allow NIH (or a contractor on NIH’s behalf) to audit this facility? Yes No How much advance notice will be required in the event an audit is to take place?

How many days would be allowed for the audit?

RAW MATERIALS AND COMPONENTS CONTROL

PURCHASING / IN-PLANT CONTROL

Are materials assigned alpha-numeric or an identifying mark for each incoming lot? Yes No Are materials visibly marked as: Sampled Approved Rejected Not Marked Is the storage area separate from other areas? Yes No Is a stock rotation system used? FI/FO FE/FO Other Is the general housekeeping maintained to ensure cleanliness and order? Yes No Is raw material acceptance based on written specifications and approval of vendor sources? Yes No Are reject/accept limits shown on suppliers Certificate of Analysis (COA)? Yes No How are retest/expiration dates assigned for raw materials and/or finished products?

Is approval based upon:

Suppliers C of A On Site Audit Internal QC Testing Other (please describe)

Are changes in specifications of products reviewed and signed off by QA/QC personnel? Yes No Is there an inventory log or record of all incoming materials? Yes No Is a computerized inventory management system used? Yes No If yes, please provide name of system:

TESTING

Are written testing procedures used to release the product? Yes No Does the laboratory use a LIMS system? Yes No If no, please describe the system in place to store lab information/data:

Are microbiological aspects specifications relevant? Yes No Are test results kept on file? Yes No Sampling plan used: 100% MIL Spec AQL Random Other:

Do test results indicate: Quantity sampled Method of Analysis Date and signature of analyst Sample traceability

RETENTIONS SAMPLES

If not applicable, check “N/A” and skip section. N/A Are retention samples of raw materials/components retained? Yes No Are retention samples of finished goods retained? Yes No Are retention samples from each production run retained? Yes No Are retention samples stored in a separate controlled area? Yes No Are retention samples in the same container/closure system in which they are sold? Yes No How long are retention samples held? years Is there a written retention sample log or file? Yes No Do you have a reduced testing program implemented at your facility? Yes No If yes, please describe:

REJECTED MATERIALS

Rejected materials are clearly marked: Yes No Are rejected products held in a segregated area? Yes No Are there written procedures for disposing of or reworking rejected items? Yes No

Are rejected products held in quarantine pending final disposition? Yes No Are rejected products identified with special markings? Yes No

MANUFACTURING

MASTER PRODUCTION RECORDS

Is there a single controlled file of master records for each product? Yes No Are these master records signed and dated? Yes No Do these master records contain revision dates? Yes No Are the process/manufacturing steps fully described:

In the master production record Yes No In a separate document or record Yes No

Is there a master document to indicate:

QC points for in-process sampling/testing Yes No Type of test or inspection to be made Yes No Method of measurement Yes No Who performs test or inspection Yes No Level of acceptance/reject (limits) Yes No Describe how the document control system for master production records works at the facility?

Is a computerized system utilized? Yes No If yes, please provide name of system:

Are critical process steps in process validated/verified and co-signed? Yes No

PRODUCTION AREA

Does your facility have a site master plan? Yes No Is there a distinct staging area for raw materials/components? Yes No Are the production or assembly lines segregated? Yes No Are general housekeeping and environmental factors good? Yes No Are written procedures for plant sanitation available? Yes No

PRODUCTION EQUIPMENT

Are maintenance or service records available? Yes No Are calibration records for critical instruments available? Yes No Is there a means of readily identifying the type and stage of processing being done on equipment?

Yes No What system is used to track calibration/PM?

If computerized, is it validated? Yes No Is equipment dedicated? Yes No If not, is cleaning verified? Yes No

PRODUCTION RECORDS

Are production records collected and filed? Yes No Kept years Are labeling samples included? Yes No How is traceability by lot number or serial number accomplished?

PACKAGING and LABELING Are finished goods packaging operations segregated? Yes No Are label records kept? Yes No Is there pre-label: count Yes No reconciliation Yes No Is there electronic verification that labeling is correct? Yes No

Are finished goods properly identified, labeled and stored? Yes No STERILE COMPONENTS (if not applicable, check box and skip this section) N/A Are there procedures for establishing and maintaining aseptic conditions? Yes No Are methods for routine auditing of sterile areas used? Yes No Are there procedures for working in sterile areas? Yes No Are there procedures for cleaning and sterilization of equipment? Yes No Are there procedures for bulk and final product sterility testing? Yes No Is process sterility for each run documented in the production records? Yes No Sterile process used: ETO Radiation Steam Filtration Chemical Other:

QUALITY CONTROL/ASSURANCE

ORGANIZATION AND FUNCTION

Who does the head of the Quality Unit report to (title)?

Does the Quality Unit have ultimate authority to withhold shipment or further processing of materials/product that have possible GMP issues? Yes No Are the Quality Units procedures: In a formal written document Yes No Revised on a periodic basis Yes No Do you have a computerized system for master documents?

Yes No Please describe the system:

Are ERES (electronic records and electronic signatures) used? Yes No

Does the Quality Unit have adequate education, training and/or experience necessary to perform their assigned duties? Yes No

Is there a file with past and current labeling for each product? Yes No Is there a formal auditing program of the QC operation? Yes No Is there a Quality Policy in place? Yes No Is there a Change Control System in place? Yes No Are batch record reviews conducted by multi-functional groups? Yes No Are procedures in place to handle deviations/investigations? Yes No Are stability programs conducted at this site?

Yes No N/A Does an OOS procedure exist?

Yes No

QUALITY OPERATIONS

Are stamps, tags, markers etc. used to verify inspection activity? Yes No Are the markings used traceable to an individual inspector? Yes No Are production samples for QC testing:

Adequately identified as to source Yes No Recorded somewhere at the time of sampling Yes No Entered on filed test report Yes No Written sampling plan is based upon: 100% MIL SPEC AQL Random

Other Is the finished product tested prior to final release? Yes No

Are outside sources used for any manufacturing, packaging or testing? Yes No Is stability testing on the finished product carried out at this facility? Yes No

CUSTOMER COMPLAINTS

Is there a group or individual assigned to handle customer inquiries and follow up on complaints?

Yes No Is there a procedure for handling complaints? Yes No Was a review of complaint files for this survey product made? Yes No Are product defects verified by manufacturer through testing? Yes No Is there an organized complaint file? Yes No What system is used to track complaints?

Is it computerized? Yes No If ‘yes’ has it been validated to be CFR Part 11 compliant? Yes No

Does each complaint state: Nature of complaint Response to customer Corrective/preventive action Complaint files are kept years Is there a periodic review of complaint files for trends? Yes No Is the review filed as a written summary? Yes No

RECALL CAPABILITIES

Is there a company recall plan? Yes No Does this plan show how decisions are made and by whom? Yes No Does this plan outline how a recall will be accomplished? Yes No Are there instructions for recovery and accountability of recalled product? Yes No Do shipping or distribution records on file show:

Customer or distributor name and address Yes No Date of shipments and quantity shipped Yes No Lot or serial number of product shipped Yes No Distribution records are maintained years Distribution records are stored as:

Paper files Computer files Microfilm

ADDITIONAL DOCUMENTATION

Please provide the following documents, if applicable

(check all that have been included):

cGMP Certification Debarment Certification TSE/BSE Statement GMO Certification Outline plans of the site to be audited, highlighting production areas.

A brief description of the ventilation systems.

A brief description of the water systems.

A brief description of major production and quality control laboratory equipment.

Organizational chart showing persons responsible for production and QA/QC.

List of all products manufactured and/or packed for NIH on site.

Provide details of any work relevant to the audit which is contracted out to other Manufacturers (e.g.

packaging, processing, sterilization, milling, analysis etc.). Please provide company names and addresses.

Provide a list of the Standard Operating Procedures (SOPs) and analytical methods used while processing NIH components.

Any further information which may be relevant to the audit.

Copy of DMF/EDMF/Technical Data Packet or Site Master File if possible.

Latest Product Quality Review for the product(s) to be audited.

A specimen of a Certificate of Analysis.

A brief description of the manufacturing process.

Most recent FDA Inspection, including any 483’s and responses.

All applicable Material Safety Data Sheet (MSDS).

Certificate of Origin (site/s material is manufactured)

Name: TBD