MANUFACTURING PRACTICE AUDIT
(GMP AUDIT – CHECKLIST)

Part 1: General Information

Name of Manufacturer

 

Physical Address

 

Drug Manufacturing license No. and Validity (Date of application for DML renewal)

 

Contact Address

 

Date of inspection

 

Purpose of inspection

 

Name of inspector (s)

 

Name of Firm’s Representative (s) accompanying during an inspection

 



General Information about the Unit:





Detail of manufacturing section(s)

Pharmacological Category(ies)

Dosage Form

Total Number of Registered products

Remarks

(if any)

 

 

 

 

 

 

 

 

 

 

 

 



Brief History of previous inspections:









The focus of the inspection:







Table of Content:

Sr. No.

Contents

1.

Quality Assurance  

2.

Premises   

3.

Personnel    

4.

Validation

5.

Documentation / Records

6.

Vendor Qualification         

7.

Change Control Program  

8.

Sample

9.

Stability Studies

10.

Drug Recall 

11.

Annual Product Review     

12.

Audits

13.

Quality Control Departments       

14.

Manufacturing Area           

 

14.1

Equipment    

 

14.1.1

Equipment Calibration

 

14.1.2

Material / Component         

 

14.2

Raw Material

 

14.3

Purified and Water for Injection Systems

 

14.4

Depack / Preparation component room

 

14.5

Sterilizer / Oven Loading Room

 

14.6

Equipment Airlock

 

14.7

Washroom / Grown change room  

 

14.8

Manufacturing (Sterile Product)

 

14.9

Aspectic Batching Area

 

14.11

Filling room

 

14.14

Terminal Sterilization

 

14.15

Packaging

 

14.16

Manufacturing (Oral dosages)

 

14.17

Packaging

15.

Reprocessing

16.

Finished Product Control

17.

Warehouse / Distribution

18.

Environment, Health & Safety



Sr. No.

 

Criteria

Yes

No

Not Applicable

(To be filled by Auditee)

To be filled by Auditor

1.0

QUALITY ASSURANCE

 

 

 

1.1

Does the company have a mission statement and a quality policy?

 

 

 

1.2

Is the company ISO certified?

 

 

 

1.3

Was the company previously audited (GMP audit)?

 

 

 

1.4

Are pharmaceutical products designed and developed according to the requirement of GMP      & other associated codes such as good laboratory practice (GLP) and good clinical practice (GCP)?

 

 

 

1.5

Are production and control operations clearly specified in a written form and GMP requirements are adopted?

 

 

 

1.6

Are managerial responsibilities clearly specified in job descriptions?

 

 

 

1.7

Are all necessary controls on starting materials, intermediate products and other in-process controls, calibrations and validation carried out?

 

 

 

1.8

Are finished products correctly processed and checked according to the defined procedures?

 

 

 

1.9

Are satisfactory arrangements existed to store in appropriate storage conditions?

 

 

 

2.0

PREMESIS

 

2.1

(DESIGN               &             LAYOUT                OF FACILITIES)

Does the facility have proper design, layout and        finishes based    on contemporary standards to:

 

 

 

2.1.1

Manufacture high-quality medicine.

 

 

 

2.1.2

Avoidance of cross-contamination.

 

 

 

2.1.3

Proper cleaning, drainage and sanitizing.

 

 

 

2.1.4

Ventilation, air conditioning and maintenance.

 

 

 

2.2

Is there an emergency power supply available to take care of the entire energy demand or at least critical areas?

 

 

 

2.3

Does the facility have appropriate controls to maintain required parameters e.g. temperature, relative humidity and pressure differentials etc?

 

 

 

2.4

Are the doors, windows, walls, ceiling and floor such that no holes or cracks are evident (other than those intended by design)?

 

 

 

2.5

PLANT SAFETY & SECURITY

 

 

 

2.5.1

Does the facility have safety program?

 

 

 

2.5.2

Are safety procedures written?

 

 

 

2.5.3

Do employees receive safety orientation before working in the plant area?

 

 

 

2.5.4

Does the facility have a formal, written security policy?

 

 

 

2.5.5

Is access to the facility restricted?

 

 

 

2.6

SANITATION

 

 

 

2.6.1

Is a written sanitation program available on the premises?

 

 

 

2.6.2

Is the sanitation program implemented and effective in preventing conditions?

 

 

 



3.0

PERSONNEL (STAFFING PLAN, STAFF QUALIFICATION, EXPERIENCE, ON-THE-JOB TRAINING & HYGIENE)

 

3.1

Has the facility provided sufficient qualified personnel to fulfill all its responsibilities required under the rule?

 

 

 

3.2

Has the facility provided Organization Chart?

 

 

 

3.3

Does the company have qualified, trained and experienced staff required for managing?

 

 

 

3.4

Does the company have “On the job training program” for technical staff?

 

 

 

3.5

Is the technical staff, including supervisors and operations certified (and documented) in specialized training e.g. aseptic technique, sterilizing, washing, dehydrogenation, visual inspection, standard operating procedure etc.

 

 

 

3.6

HYGIENE

 

 

 

3.6.1

Are all the personnel undergone health examinations to prior to employment? Are all the personnel provided health examinations during employment?

 

 

 

3.6.2

Are workers conducting visual inspections undergoing periodic eye examinations?

 

 

 

3.6.3

are the record maintained?

 

 

 

3.6.4

Are all personal aware of the principles of GMP and received initial

 

 

 

3.6.5

and continued training including hygiene instructions?

 

 

 

4.0

VALIDATION

 

4.1

Is validation properly documented and includes Validation Master Plan, Validation Protocols, Validation Reports and Equipment Qualified?

 

 

 

4.2

Are validation studies conducted in accordance with pre-defined protocols?

 

 

 

4.3

Have production procedures been validated?

 

 

 

4.4

Does the process control address an issue to ensure the identity, strength, quality and purity of the product?

 

 

 

4.5

Does the procedure include formulation that is written to yield not less than 100% of the established amount of active ingredients?

 

 

 

4.6

Are all weighing and measuring performed by one qualified person and observed by a second person and is dully signed by both of them on record sheet?

 

 

 

4.7

Validation of New Master Formula:

Is new master formula or method of preparation adopted and steps taken to demonstrate its suitability for routine processing, process defined materials and equipment specified?

 

 

 

4.8

Validation of Equipment & Materials:

Are significant amendments to the manufacturing process, including any change in equipment and materials affecting product quality or re-productivity of process validated?

 

 

 

4.9

Are validation records properly maintained?

 

 

 



5.0

DOCUMENTATION / RECORDS

 

5.1

Are documentation meticulously maintained as per rules and regularly reviewed and kept up to date?

 

 

 

5.2

Is documentation accurate, clear & neat? Does it define specifications and procedures for all materials & methods of manufacture & control?

 

 

 

5.3

Are all the specifications, testing procedures, master formulae, packing instructions and standard operating procedures (SOPs) available, current & being followed?

 

 

 

5.4

Do the records provide the existence of documented evidence, traceability, and an audit trial that will permit investigation?

 

 

 

5.5

Does the record provide batch processing & packaging details including receiving sample, processing equipment, analytical testing and laboratory instrument records?

 

 

 

5.6

LABELS

 

 

 

5.6.1

Are labels to the containers, equipment or premises applied un- ambiguously according to the company’s agreed format?

 

 

 

5.6.2

Are labels of different colors indicating the status such as “Quarantined”,

 

 

 

5.6.3

Are all finished products are labeled as per specification?

 

 

 

5.6.4

PROCESS DOCUMENTATION / RECORDS

 

 

 

Are following documents/record are available:

 

 

 

 

Starting material re-assy.

 

 

 

Specifications for intermediate and bulk products

 

 

 

Batch processing records

 

 

 

Record for process operation

 

 

 

Batch packaging records

 

 

 

Record for packaging operation

 

 

 

Record of Batch numbers

 

 

 

Analytical records of the batch Record for finished product release procedure

 

 

 

5.7

STANDARD OPERATING PROCEDURES (SOPS)

 

 

 

 

Are SOPS and associated records of actions, and conclusions reached available for the following at the premises?

 

 

 

Equipment assembly and validation

 

 

 

 Analytical apparatus and calibration

 

 

 

Maintenance, cleaning and sanitization

 

 

 

Personnel matters including qualification, training, clothing and hygiene

 

 

 

Environmental monitoring

 

 

 

Pest control

 

 

 

Complaints

 

 

 

Drug recalls

 

 

 

Drug returns

 

 

 

5.8

EQUIPMENT LOG BOOKS

 

 

 

5.8.1

Are log books for major & critical equipment identified by the company kept?

 

 

 

6.0

VENDOR QUALIFICATION

 

6.1

Do you have list of approved vendors?

 

 

 

6.2

Are the vendors supplying raw material (both active & inactive ingredients), empty gelatin capsules, primary packaging & printed packaging components audited & found to be satisfactory?

 

 

 

7.0

CHANGE CONTROL PROGRAM

 

7.1

Is there a formal change control program in place supported by an SOP to initiate, review & approve changes in material, sources, processes, products packaging, equipment, batch size changes etc.

 

 

 

8.0

SAMPLE

 

8.1

Does the company retain a sample of lot or batch of the packaged/labeled drug for a period of at least one year after the expiration date on the label of the drug?

 

 

 

8.2

Does the company retain a sample of each lot or batch of a raw material (including both active and inactive ingredients)?

 

 

 



9.0

STABILITY STUDIES

 

9.1

Does the company have a prospective and concurrent stability studies program based on SOP and utilizing proper equipment i.e. climatic chambers maintained at 30° C / 65% RH for ambient and 40° C / 75% RH for stress conditions and continuously monitored for temperature & RH?

 

 

 

9.2

Is stability of finished products evaluated and documented prior to marketing?

 

 

 

9.3

Does the stability data support shelf life assigned to the product. Are any deviations in data reviewed and appropriate steps taken in case of stability issues?

 

 

 

10.0

DRUG RECALL

 

10.1

Do you have SOP for drug recalls?

 

 

 

10.2

If answer yes to the above did you have any drug recall in the past 2 year? (Please also mention the name of products)

 

 

 

11.0

ANNUAL PRODUCT REVIEW

 

11.1

Is there a process in place to review statistical data (i.e.: trend analysis, reworks, rejects, customer complaints) of all the products manufacture during the year?

 

 

 

11.2

Provide name of the products manufactured by you along with price list.

 

 

 

11.3

Provide the source of raw material for individual products.

 

 

 

11.4

Do you export your products, if so then to whom and mention the name of the products?

 

 

 

12.0

AUDIT / COMPLAINTS

 

12.1

INTERNAL GMP AUDITS

 

 

 

12.1.1

Do you have an effective internal GMP inspection program to audit all the manufacturing areas, activities & QC lab at specific defined periods?

 

 

 

12.1.2

Is there a process in place to fill the gaps / observation / non-conformance found during the internal GMP audits?

 

 

 

12.2

QUALITY AUDITS

 

 

 

 

Is quality audit conducted by outside or independent specials or a team designated by the management for the purpose?

 

 

 

12.3

COMPLAINTS

 

 

 

 

Are complaints and other information concerning potentially defective products carefully reviewed according to the written procedures?

 

 

 

13.0

QUALITY CONTROL DEPARTMENT

 

13.1

Does the QC lab have SOPs to cover all the functional areas?

 

 

 

13.2

Are adequate facilities and equipments available for the physical, chemical & microbiological testing?

 

 

 

13.3

Are approved written procedures available for sampling, inspecting and testing raw materials, packaging materials, in process drugs, bulk drugs and finished products?

 

 

 

13.4

Are samples of starting material, packaging material, intermediate products, bulk products and finished products taken by methods and personnels approved by QC department?

 

 

 

13.5

Are in-process materials tested at appropriate phases for identity, strength, quality, purity and are they approved or rejected by Quality Control?

 

 

 

13.6

Are records of in- process controls maintained?

 

 

 

13.7

Does each batch of drug product prior to release confirms compliance of finished product specification?

 

 

 

13.8

Are validated & stability indicating assay methods used?

 

 

 

13.9

Are reference standards used for the assay?

 

 

 

13.10

Are accurate, clear & neat records maintained along with the raw data for the entire analytical work?

 

 

 



14.0

MANUFACTURING AREA EQUIPMENTS, 

EQUIPMENTS, MATERIAL / COMPONENT

 

14.1

EQUIPMENTS

 

 

 

 

Does the company have suitable equipments capable of producing consistent quality products?

 

 

 

Do the equipments meet contemporary standards for the manufacture of pharmaceuticals i.e. smooth finishes, right quality construction material for the intended purpose, easy to clean, wash, sterilize etc.

 

 

 

Are the following pieces of equipments suitable in their design/size & capacity? (Blends, Conveyors, Tablet presses, Capsule fillers, Bottle fillers etc)

 

 

 

Does the equipments & facilities have appropriate controls to maintain required parameters e.g. temperature, relative humidity, pressure differentials etc?

 

 

 

Is the equipment cleaned promptly after use?

 

 

 

14.2

EQUIPMENT/INSTRUMENTS CALIBRATION & PREVENTIVE MAINTENANCE

 

 

 

 

Are written records maintained on equipment cleaning, sanitizing and maintenance on or near each piece of equipment?

 

 

 

Does the facility have approved written procedures for checking and calibration of each piece of measurement equipment?

 

 

 

Are records of calibration checks and inspections maintained in a readily retire able manner?

 

 

 

14.3

MATERIAL/COMPONENT

 

 

 

 

All handling of material and products such as receipt, quarantine, sample storage,

 

 

 

All incoming materials and finished products quarantined immediately after receipt or processing until they released for use or distribution?

 

 

 

Are all materials handled in such a way to prevent contamination?

 

 

 

14.4

RAW MATERIAL

 

 

 

 

Were the premises designed for storing the raw material?

 

 

 

Does the store premises allow storage of raw materials at various temperatures?

 

 

 

If answer yes to the above what are the controls to log any irregularities?

 

 

 

What is the source of the active ingredient used?

 

 

 

What are the source of additives used?

 

 

 

Is any documentation done at the time of receiving the raw materials?

 

 

 

What is the process of communication with the laboratory for a sampling of the raw material?

 

 

 

Is there a quarantine for storing unreleased raw materials?

 

 

 

If so, what is the process?

 

 

 

What is the process of storage after the raw material is released for use?

 

 

 

What is the process of issue of raw material for manufacturing?

 

 

 

Who is responsible of issuing?

 

 

 

What is the process of revalidation of balances?

 

 

 

What is the process of revalidation of raw materials?

 

 

 

Do you have a standard operational procedural manual for stores?

 

 

 

14.5

PURIFIED AND WATER FOR INJECTION SYSTEM

 

 

 

 

Does the facility have proper Purified and Water for Injection System available?

 

 

 

Is water circulating in a continuous loop and maintained at 80° C, 24/07/365?

 

 

 

Is quality of water monitored chemically & biologically on daily basis?

 

 

 

Is purified water used in all oral preparation & washing of equipment? Is water for injection used for all sterile preparation, clean steam generation for autoclaving, final rinse of machine parts and sterile container?

 

 

 

Are deionizers that feed water for injection of two bed design and able to provide for continuous flow?

 

 

 

Are stills constructed of stainless steel?

 

 

 

If yes what type?

 

 

 

Are still equipped with devices which measure, record and automatically control conductivity?

 

 

 

Have the stills been passivated?

 

 

 

Are the holding tanks electropolished and passivated?

 

 

 

Are the holding tanks electro polished and passivated?

 

 

 

Are the holding tanks equipped with heated or jacketed 0.2-micron hydrophobic filter?

 

 

 

Are the holding tanks capable of steam sterilization at a minimum of 121° C?

 

 

 

Are holding tanks equipped tanks equipped to maintain WFI at 80 °C?

 

 

 

Are the holding tanks equipped to supply nitrogen through a 0.2-micron hydrophobic vent filter?

 

 

 

If WFI system constructed of stainless steel 316 L or equivalent?

 

 

 

Is WFI system electro polished and passivated?

 

 

 

Is there a continuous loop, single pass system?

 

 

 

Is the system sloped with dead legs no larger than 6 pipe diameters?

 

 

 

Is the system fitted with diaphragm values?

 

 

 

Is the system capable of steam sterilization?

 

 

 

Is the system capable of being maintained at 80 °C with continous temperature monitoring devices?

 

 

 

Is the conductivity of WFI monitored on return loop?

 

 

 

Are pumps constructed of stainless steel, 316 L or equivalent?

 

 

 

Do the pumps use WFI as seal lubricant?

 

 

 

Are pumps able to be completely drained?

 

 

 

What is the source of water to the facility?

 

 

 

Well / City water / Treated / Untreated

 

 

 

Is testing performed on dionized water system which supplies the NFI system?

 

 

 

What tests are performed?

 

 

 

How frequently are they performed? Are the results documented?

 

 

 

Are there heat exchangers with in WFI system?

 

 

 

What is the type of heat exchangers

 

 

 

316 L / Double sheet type/ double concentric tube type?

 

 

 

What is the type and porosity of filters within WFI system?

 

 

 

Which department performs the validation of WFI system?

 

 

 

Was the validation approved by QC/QA?

 

 

 

Was the report issued and forwarded to worldwide QC/QA?

 

 

 

Do you have SOP written for WFI?

 

 

 

Is WFI tested when used as raw material as per testing standard Z 5576 requirements?

 

 

 

Are the results documented?

 

 

 

Are the all-use points in WFI system tested as per testing standard Z 5576 on weekly basis?

 

 

 

Are the results documented?

 

 

 

Have microbial limits been established for WFI samples?

 

 

 

What action plan exists in the event the microbial limits exceed?

 

 

 

 

Is the investigation documented? What is the porosity of membranes used in microbiological testing?

 

 

 

What nutrient media is used?

 

 

 

At what temperature and for how long are WFI samples incubated?

 

 

 

After incubation how are results documented?

 

 

 

Are any microorganisms that are isolated from positive WFI samples gram stained and/or identified to genus/species?

 

 

 

Are standardized and validated autoclave loads for nutrient media used for WFI testing?

 

 

 

Are growth support tests performed on each lot of nutrient media that is used for WFI testing?

 

 

 

How is sterility verified for each lot of nutrient media that is used for WFI testing?

 

 

 

How is nutrient media stored prior to use?

 

 

 

Are there established routine maintenance/calibration programs for deionized and WFI systems?

 

 

 



14.6

DEPACK / PREPARATION COMPONENT ROOM

 

 

 

 

Is the depack room separate from the component preparation room?

 

 

 

Does depack room have air conditioning and local exhaust for dust control?

 

 

 

Is there a pass through between the depack room and the component preparation room?

 

 

 

Is there a uniform change room outside of the preparation component room?

 

 

 

Is access to the preparation component room restricted?

 

 

 

What is the preparation component room designated class?

What is the efficiency of filters?           %

How many air changes occur per hour?

 

 

 

 

 

 

 

 

 

What type of water is supplied to washer and sinks?

 

 

 

What is the validation process for the washing of stopper & vials?

 

 

 

How are the silicone vials and stopper tested for use?

 

 

 

Are Stopper and vials tagged with lot numbers as such through sterilization/dehydrogenation and on through filling

 

 

 

How frequently are efficiency filters and laminar flow hood heap filters tested?

 

 

 

Are the garments made of non- shredding material?

 

 

 

What is the frequency of the garments being sterilized?

 

 

 

14.7

STERILIZER / OVEN LOADING ROOM

 

 

 

 

What is the sterilizer / oven loading room designated class?

 

 

 

What is the efficiency of filters?

 

 

 

How many air changes occur per hour?

 

 

 

Does the sterilizer meet the following criteria:

 

 

 

Is it capable of maintaining an empty chamber temperature distribution of +/- 1° C at a steady state?

Is there a double door design with interlock?

 

 

 

What is the size of vent filter?

 

 

 

Is it capable of using thermocouples in the chamber for measuring load temperatures?

 

 

 

Is it equipped with a recording device for checking temperature and pressure?

 

 

 

Is it equipped with a vacuum pump for the removal of air from the load?

 

 

 

Is it equipped with a clean steam?

 

 

 

Does the oven meet the following criteria?

 

 

 

Is it equipped with hepa filtered air?

 

 

 

Are there 2 inter locking doors?

 

 

 

Are there recirculating fans located upstream of the HEPA filters?

 

 

 

Does it have the resistance temperature device in the return air duct for control temperature?

 

 

 

Can it maintain an empty chamber

 

 

 

+/- 20 °C for sterilization?

 

 

 

Is it equipped with a temperature recorder?

 

 

 

Can be fitted with additional temperature probes for measuring loaded materials?

 

 

 

How frequently are the sterilizer and oven calibrated and the results documented?

 

 

 

How frequently are the efficiency filters integrity tested?

 

 

 

Are the results of the testing documents?

 

 

 

Are the garments made of non sharedding material?

 

 

 

Are the garments washed and sterilized after use?

 

 

 

How frequently are they sterilized? Are the procedures validated for the sterilized/depyrogenated stoppers and components?

 

 

 

Are biological or chemical indicators used?

 

 

 

Are stoppers and components used for a given lot of product traceable via a lot number to a specific sterilizer/oven load?

 

 

 

How long can the of sterilized/depyrogenated components be stored prior use?

 

 

 

Are the processes for storage of sterilized /depyrogenated components validated?

 

 

 

Are the sterilizer and oven charts reviewed by Quality Control prior to the release of sterile products?

 

 

 

Have restrictions been established for the number of times that components may be sterilized /depyrogenated?

 

 

 



14.6

EQUIPMENT AIRLOCK

 

 

 

 

Are the air lock doors interlocked double room concept?

 

 

 

Is the airlock designated class 100,000?

 

 

 

Are there low-level air returns? What is the air flow from?

 

 

 

Does the airlock have lights?

Ultraviolet

Infra-Red

 

 

 

 

 

 

 

 

 

Is the airlock equipped for spray sanitization?

 

 

 

What sanitizing agent is used?

 

 

 

14.7

WASHROOM / GOWN CHANGE ROOM

 

 

 

 

Is the wash room equipped with sink and hot air hand drivers?

 

 

 

Does the wash room have lights?

Ultraviolet

Infra-Red

 

 

 

 

 

 

 

 

 

Does the wash room have interlocked doors?

 

 

 

Is there an airlock entry from the grown change room into the

 

 

 

Sterile rooms?

 

 

 

Is the grown change room designed as class 100,000?

 

 

 

Are garments made of non-shredding material?

 

 

 

How frequently are they sterilized?

 

 

 

What sanitization agent is used?

 

 

 

14.8

MANUFACTURING (STERILE PRODUCTS)

 

 

 

 

Does the company have adequate sterilizing, depyrogenating, sterile, filtration, processing, filling and packaging equipment available?

 

 

 

Is there an adequate control of viable, non-viable micro-organisms and effective routine monitoring of sterile area and aseptic practices through use of reliable equipment?

 

 

 

Are sterile area air handling unit run 24/7 except for shut down due to routine maintenance to maintain sterile environment?

 

 

 

14.9

ENVIRONMENTAL MONITORING

 

 

 

 

Are laminar flow hood and HVAC system which serve the sterile operations areas validated?

 

 

 

Which department performs the validation?

 

 

 

Was the validation approved by QC/QA?

 

 

 

Was the report issued?

 

 

 

If yes, was the report forwarded to worldwide QC/QA?

 

 

 

Is there an environmental monitoring program for the aseptic batching area, sterile filling room, sterile filling line and ancillary areas?

 

 

 

Is non-viable particulate sampling performed?

 

 

 

How is viable air sampling performed?

 

 

 

How is surface sampling performed?

 

 

 

Is environmental monitoring equipment on a maintenance / calibration program?

 

 

 

At what temperature for how long are environmental monitoring samples incubated?

 

 

 

After incubation how are test results documented?

 

 

 

What nutrient media is used for environmental monitoring?

 

 

 

Are there standardized and validated autoclave loads for nutrient media used for environmental monitoring?

 

 

 

Are growth support tests performed on each lot of nutrient media that is used for environmental monitoring?

 

 

 

How is sterility verified for each lot of nutrient media that is used for environmental monitoring?

 

 

 

How is nutrient media stored prior to use?

 

 

 

14.10

ASCEPTIC BATCHING AREA

 

 

 

 

Is the area designated as class 10,000? Are there terminal Hepa filters?

 

 

 

What is the minimum of air changes per hour?

 

 

 

Is the area capable of complying with the maximum temperature (68° F) and humidity limits (50% RH)?

 

 

 

Do the laminar flow hoods provide class 100 air over the product?

 

 

 

Is all the product contact equipment in the aseptic batching area sterilizable by hot air or steam?

 

 

 

Are the walls, floors and ceilings non porous and sanitizable?

 

 

 

Are the doors self-closing without door knobs?

 

 

 

Are the light fixtures and motors totally sealed and enclosed?

 

 

 

Are the room air pressures, temperature, humidity and filter pressure drop automatically monitored, alarmed and recorded?

 

 

 

Do personnel sanitize their gloved hands?

 

 

 

Are HEPA filters and laminar flow hoods integrity tested?

 

 

 

If yes, how frequently?

 

 

 

Is equipment status labeled?

 

 

 

Are the results documented for the equipments calibrated?

 

 

 

Are sterilization/clarification filters integrity tested and results documented

 

 

 

What is the quality of water used for equipment cleaning?

 

 

 

Are tanks, hoses etc. sterilized prior to use and are these procedures user validated?

 

 

 

Are tanks labeled during processing indicating status of product?

 

 

 

Are asceptic operations performed using laminar flow hoods?

 

 

 

Is sterile bulk sampled and tested as per testing standard requirements?

 

 

 

Are sampling and testing complete prior to or concurrent with the filling operation?

 

 

 

Is bulk held under positive pressure after final filtration / sterilization?

 

 

 

How are gases sterilized?

 

 

 

Is sterile gas filters integrity tested before and / or after use?

 

 

 

How is bulk yield determined? Are batches reprocessed?

 

 

 

If so, what are the written procedures?

 

 

 

Is rework material routinely added to batches?

 

 

 

14.11

FILLING ROOMS

 

 

 

 

Is the filling room designated as class 10,000?

 

 

 

What are the minimum air changes per hour?

 

 

 

Are environmental systems designed to run continuously?

 

 

 

Is the area capable of complying with maximum temperature (68 °F) and humidity limits (50%RH)?

 

 

 

Do this laminar flow hoods provide class 100 air over product?

 

 

 

Is the product contact equipment sterilized by hot air or steam?

 

 

 

Are the walls, floors and ceilings non- porous and sanitizable?

 

 

 

Are the doors self-closing without door knobs?

 

 

 

Are the light fixtures and motors totally sealed and enclosed?

 

 

 

Are room air pressure, temperature, humidity and filter pressure drop automatically monitored, alarmed and recorded?

 

 

 

Are the filling lines designed with laminar flow hoods to provide class 100 air at the rate of 90feet/minute at the product height?

 

 

 

Are surfaces of laminar flow hood made of stainless steel?

 

 

 

Is the filling line equipped with continuous non-hinged, non-shedding sanitizable belt or conveyor system?

 

 

 

Is the filling line equipped with automatic filling and stoppering equipment?

 

 

 

What sanitizing agent is used to sanitize gloved hands?

 

 

 

Are Hepa filters and laminar flow hoods integrity tested? If yes, how frequently?

 

 

 

How is the product delivered from aseptic batching area to the filling lines?

 

 

 

Is the sterile bulk filtered on line?

 

 

 

Is the sterile filter integrity tested before and/or after use?

 

 

 

Is the porosity and type of filter included with the batch records?

 

 

 

Are results of filter integrity test included with the batch records?

 

 

 

Is bulk held under positive pressure during filling operation?

 

 

 

How are gases sterilized?

 

 

 

Are asceptic operations performed using laminar flow hoods?

 

 

 

How is the filling figure determined? Is the fill volume checked during filling operation?

 

 

 

Are the results documented?

 

 

 

What action is taken when filling limits are exceeded?

 

 

 

Are vials flooded with nitrogen? Where are the vials capped?

 

 

 

Are rejected vials reprocessed?

 

 

 

If so what are the written procedures? Is QC/QA informed of manufacturing problems that could affect product quality? (Alert Notice System).

 

 

 

What is the quality of water used for equipment cleaning?

 

 

 

What filling equipment parts are sterilized /depyrogenated in an autoclave oven prior to use?

 

 

 

Have these processes been validated? How frequently are the filling line (including accessories) sanitzed?

 

 

 

What sanitization agents are used?

 

 

 

Are the procedures validated and documented?

 

 

 

Is a filling line use record kept?

 

 

 



14.12

SANITIZATION OF STERILE ROOMS

 

 

 

 

How frequently is the sterile area sanitized?

 

 

 

What areas are sanitized? Floor / Wall / Ceilings

 

 

 

What sanitizing agents are used? Are sanitizing agents rotated?

 

 

 

Are sanitizing agents prepared with WFI and filter sterilized prior to use?

 

 

 

How is it applied to surfaces?

 

 

 

Is sanitization agent allowed to dry and then rinsed off with WFI?

 

 

 

Is sanitization documented?

 

 

 

14.13

INSPECTION

 

 

 

 

Are filled vials inspected for particulars and container defects prior to packing?

 

 

 

What percentage of batch is inspected?

 

 

 

Are the types of rejected vials documented?

 

 

 

Are rejected vials reprocessed?

 

 

 

Is there a written procedure for handling rejected vials?

 

 

 

Are inspectors trained?

 

 

 

Is the training documented?

 

 

 

Do inspectors receive an eye examination?

 

 

 

If yes, how frequently?

 

 

 

14.14

TERMINAL STERILIZATION