Name of Manufacturer |
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Physical Address |
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Drug Manufacturing license No. and Validity (Date of application for DML renewal) |
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Contact Address |
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Date of inspection |
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Purpose of inspection |
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Name of inspector (s) |
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Name of Firm’s Representative (s) accompanying during an inspection |
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General Information about the Unit:
Detail of manufacturing section(s)
Pharmacological Category(ies) | Dosage Form | Total Number of Registered products | Remarks (if any) |
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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 | Aseptic 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 |
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1.1 | Does the company have a mission statement and a quality policy? |
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1.2 | Is the company ISO certified? |
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1.3 | Was the company previously audited (GMP audit)? |
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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)? |
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1.5 | Are production and control operations clearly specified in a written form and GMP requirements are adopted? |
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1.6 | Are managerial responsibilities clearly specified in job descriptions? |
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1.7 | Are all necessary controls on starting materials, intermediate products and other in-process controls, calibrations and validation carried out? |
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1.8 | Are finished products correctly processed and checked according to the defined procedures? |
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1.9 | Are satisfactory arrangements existed to store in appropriate storage conditions? |
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2.0 | PREMESIS |
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2.1 | (DESIGN & LAYOUT OF FACILITIES) Does the facility have proper design, layout and finishes based on contemporary standards to: |
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2.1.1 | Manufacture high-quality medicine. |
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2.1.2 | Avoidance of cross-contamination. |
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2.1.3 | Proper cleaning, drainage and sanitizing. |
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2.1.4 | Ventilation, air conditioning and maintenance. |
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2.2 | Is there an emergency power supply available to take care of the entire energy demand or at least critical areas? |
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2.3 | Does the facility have appropriate controls to maintain required parameters e.g. temperature, relative humidity and pressure differentials etc? |
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2.4 | Are the doors, windows, walls, ceiling and floor such that no holes or cracks are evident (other than those intended by design)? |
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2.5 | PLANT SAFETY & SECURITY |
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2.5.1 | Does the facility have safety program? |
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2.5.2 | Are safety procedures written? |
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2.5.3 | Do employees receive safety orientation before working in the plant area? |
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2.5.4 | Does the facility have a formal, written security policy? |
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2.5.5 | Is access to the facility restricted? |
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2.6 | SANITATION |
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2.6.1 | Is a written sanitation program available on the premises? |
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2.6.2 | Is the sanitation program implemented and effective in preventing conditions? |
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3.0 | PERSONNEL (STAFFING PLAN, STAFF QUALIFICATION, EXPERIENCE, ON-THE-JOB TRAINING & HYGIENE) |
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3.1 | Has the facility provided sufficient qualified personnel to fulfill all its responsibilities required under the rule? |
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3.2 | Has the facility provided Organization Chart? |
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3.3 | Does the company have qualified, trained and experienced staff required for managing? |
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3.4 | Does the company have “On the job training program” for technical staff? |
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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. |
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3.6 | HYGIENE |
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3.6.1 | Are all the personnel undergone health examinations to prior to employment? Are all the personnel provided health examinations during employment? |
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3.6.2 | Are workers conducting visual inspections undergoing periodic eye examinations? |
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3.6.3 | are the record maintained? |
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3.6.4 | Are all personal aware of the principles of GMP and received initial |
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3.6.5 | and continued training including hygiene instructions? |
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4.0 | VALIDATION |
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4.1 | Is validation properly documented and includes Validation Master Plan, Validation Protocols, Validation Reports and Equipment Qualified? |
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4.2 | Are validation studies conducted in accordance with pre-defined protocols? |
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4.3 | Have production procedures been validated? |
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4.4 | Does the process control address an issue to ensure the identity, strength, quality and purity of the product? |
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4.5 | Does the procedure include formulation that is written to yield not less than 100% of the established amount of active ingredients? |
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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? |
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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? |
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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? |
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4.9 | Are validation records properly maintained? |
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5.0 | DOCUMENTATION / RECORDS |
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5.1 | Are documentation meticulously maintained as per rules and regularly reviewed and kept up to date? |
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5.2 | Is documentation accurate, clear & neat? Does it define specifications and procedures for all materials & methods of manufacture & control? |
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5.3 | Are all the specifications, testing procedures, master formulae, packing instructions and standard operating procedures (SOPs) available, current & being followed? |
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5.4 | Do the records provide the existence of documented evidence, traceability, and an audit trial that will permit investigation? |
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5.5 | Does the record provide batch processing & packaging details including receiving sample, processing equipment, analytical testing and laboratory instrument records? |
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5.6 | LABELS |
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5.6.1 | Are labels to the containers, equipment or premises applied un- ambiguously according to the company’s agreed format? |
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5.6.2 | Are labels of different colors indicating the status such as “Quarantined”, |
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5.6.3 | Are all finished products are labeled as per specification? |
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5.6.4 | PROCESS DOCUMENTATION / RECORDS |
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Are following documents/record are available: |
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| Starting material re-assy. |
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Specifications for intermediate and bulk products |
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Batch processing records |
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Record for process operation |
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Batch packaging records |
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Record for packaging operation |
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Record of Batch numbers |
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Analytical records of the batch Record for finished product release procedure |
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5.7 | STANDARD OPERATING PROCEDURES (SOPS) |
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| Are SOPS and associated records of actions, and conclusions reached available for the following at the premises? |
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Equipment assembly and validation |
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Analytical apparatus and calibration |
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Maintenance, cleaning and sanitization |
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Personnel matters including qualification, training, clothing and hygiene |
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Environmental monitoring |
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Pest control |
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Complaints |
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Drug recalls |
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Drug returns |
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5.8 | EQUIPMENT LOG BOOKS |
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5.8.1 | Are log books for major & critical equipment identified by the company kept? |
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6.0 | VENDOR QUALIFICATION |
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6.1 | Do you have list of approved vendors? |
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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? |
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7.0 | CHANGE CONTROL PROGRAM |
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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. |
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8.0 | SAMPLE |
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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? |
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8.2 | Does the company retain a sample of each lot or batch of a raw material (including both active and inactive ingredients)? |
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9.0 | STABILITY STUDIES |
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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? |
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9.2 | Is stability of finished products evaluated and documented prior to marketing? |
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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? |
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10.0 | DRUG RECALL |
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10.1 | Do you have SOP for drug recalls? |
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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) |
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11.0 | ANNUAL PRODUCT REVIEW |
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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? |
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11.2 | Provide name of the products manufactured by you along with price list. |
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11.3 | Provide the source of raw material for individual products. |
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11.4 | Do you export your products, if so then to whom and mention the name of the products? |
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12.0 | AUDIT / COMPLAINTS |
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12.1 | INTERNAL GMP AUDITS |
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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? |
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12.1.2 | Is there a process in place to fill the gaps / observation / non-conformance found during the internal GMP audits? |
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12.2 | QUALITY AUDITS |
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| Is quality audit conducted by outside or independent specials or a team designated by the management for the purpose? |
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12.3 | COMPLAINTS |
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| Are complaints and other information concerning potentially defective products carefully reviewed according to the written procedures? |
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13.0 | QUALITY CONTROL DEPARTMENT |
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13.1 | Does the QC lab have SOPs to cover all the functional areas? |
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13.2 | Are adequate facilities and equipments available for the physical, chemical & microbiological testing? |
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13.3 | Are approved written procedures available for sampling, inspecting and testing raw materials, packaging materials, in process drugs, bulk drugs and finished products? |
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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? |
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13.5 | Are in-process materials tested at appropriate phases for identity, strength, quality, purity and are they approved or rejected by Quality Control? |
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13.6 | Are records of in- process controls maintained? |
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13.7 | Does each batch of drug product prior to release confirms compliance of finished product specification? |
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13.8 | Are validated & stability indicating assay methods used? |
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13.9 | Are reference standards used for the assay? |
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13.10 | Are accurate, clear & neat records maintained along with the raw data for the entire analytical work? |
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14.0 | MANUFACTURING AREA EQUIPMENTS, EQUIPMENTS, MATERIAL / COMPONENT |
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14.1 | EQUIPMENTS |
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| Does the company have suitable equipments capable of producing consistent quality products? |
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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. |
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Are the following pieces of equipments suitable in their design/size & capacity? (Blends, Conveyors, Tablet presses, Capsule fillers, Bottle fillers etc) |
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Does the equipments & facilities have appropriate controls to maintain required parameters e.g. temperature, relative humidity, pressure differentials etc? |
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Is the equipment cleaned promptly after use? |
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14.2 | EQUIPMENT/INSTRUMENTS CALIBRATION & PREVENTIVE MAINTENANCE |
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| Are written records maintained on equipment cleaning, sanitizing and maintenance on or near each piece of equipment? |
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Does the facility have approved written procedures for checking and calibration of each piece of measurement equipment? |
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Are records of calibration checks and inspections maintained in a readily retire able manner? |
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14.3 | MATERIAL/COMPONENT |
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| All handling of material and products such as receipt, quarantine, sample storage, |
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All incoming materials and finished products quarantined immediately after receipt or processing until they released for use or distribution? |
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Are all materials handled in such a way to prevent contamination? |
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14.4 | RAW MATERIAL |
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| Were the premises designed for storing the raw material? |
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Does the store premises allow storage of raw materials at various temperatures? |
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If answer yes to the above what are the controls to log any irregularities? |
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What is the source of the active ingredient used? |
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What are the source of additives used? |
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Is any documentation done at the time of receiving the raw materials? |
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What is the process of communication with the laboratory for a sampling of the raw material? |
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Is there a quarantine for storing unreleased raw materials? |
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If so, what is the process? |
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What is the process of storage after the raw material is released for use? |
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What is the process of issue of raw material for manufacturing? |
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Who is responsible of issuing? |
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What is the process of revalidation of balances? |
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What is the process of revalidation of raw materials? |
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Do you have a standard operational procedural manual for stores? |
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14.5 | PURIFIED AND WATER FOR INJECTION SYSTEM |
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| Does the facility have proper Purified and Water for Injection System available? |
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Is water circulating in a continuous loop and maintained at 80° C, 24/07/365? |
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Is quality of water monitored chemically & biologically on daily basis? |
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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? |
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Are deionizers that feed water for injection of two bed design and able to provide for continuous flow? |
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Are stills constructed of stainless steel? |
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If yes what type? |
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Are still equipped with devices which measure, record and automatically control conductivity? |
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Have the stills been passivated? |
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Are the holding tanks electropolished and passivated? |
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Are the holding tanks electro polished and passivated? |
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Are the holding tanks equipped with heated or jacketed 0.2-micron hydrophobic filter? |
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Are the holding tanks capable of steam sterilization at a minimum of 121° C? |
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Are holding tanks equipped tanks equipped to maintain WFI at 80 °C? |
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Are the holding tanks equipped to supply nitrogen through a 0.2-micron hydrophobic vent filter? |
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If WFI system constructed of stainless steel 316 L or equivalent? |
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Is WFI system electro polished and passivated? |
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Is there a continuous loop, single pass system? |
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Is the system sloped with dead legs no larger than 6 pipe diameters? |
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Is the system fitted with diaphragm values? |
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Is the system capable of steam sterilization? |
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Is the system capable of being maintained at 80 °C with continous temperature monitoring devices? |
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Is the conductivity of WFI monitored on return loop? |
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Are pumps constructed of stainless steel, 316 L or equivalent? |
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Do the pumps use WFI as seal lubricant? |
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Are pumps able to be completely drained? |
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What is the source of water to the facility? |
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Well / City water / Treated / Untreated |
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Is testing performed on dionized water system which supplies the NFI system? |
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What tests are performed? |
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How frequently are they performed? Are the results documented? |
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Are there heat exchangers with in WFI system? |
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What is the type of heat exchangers |
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316 L / Double sheet type/ double concentric tube type? |
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What is the type and porosity of filters within WFI system? |
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Which department performs the validation of WFI system? |
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Was the validation approved by QC/QA? |
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Was the report issued and forwarded to worldwide QC/QA? |
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Do you have SOP written for WFI? |
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Is WFI tested when used as raw material as per testing standard Z 5576 requirements? |
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Are the results documented? |
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Are the all-use points in WFI system tested as per testing standard Z 5576 on weekly basis? |
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Are the results documented? |
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Have microbial limits been established for WFI samples? |
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What action plan exists in the event the microbial limits exceed? |
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| Is the investigation documented? What is the porosity of membranes used in microbiological testing? |
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What nutrient media is used? |
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At what temperature and for how long are WFI samples incubated? |
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After incubation how are results documented? |
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Are any microorganisms that are isolated from positive WFI samples gram stained and/or identified to genus/species? |
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Are standardized and validated autoclave loads for nutrient media used for WFI testing? |
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Are growth support tests performed on each lot of nutrient media that is used for WFI testing? |
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How is sterility verified for each lot of nutrient media that is used for WFI testing? |
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How is nutrient media stored prior to use? |
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Are there established routine maintenance/calibration programs for deionized and WFI systems? |
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14.6 | DEPACK / PREPARATION COMPONENT ROOM |
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| Is the depack room separate from the component preparation room? |
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Does depack room have air conditioning and local exhaust for dust control? |
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Is there a pass through between the depack room and the component preparation room? |
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Is there a uniform change room outside of the preparation component room? |
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Is access to the preparation component room restricted? |
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What is the preparation component room designated class? What is the efficiency of filters? % How many air changes occur per hour? |
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What type of water is supplied to washer and sinks? |
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What is the validation process for the washing of stopper & vials? |
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How are the silicone vials and stopper tested for use? |
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Are Stopper and vials tagged with lot numbers as such through sterilization/dehydrogenation and on through filling |
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How frequently are efficiency filters and laminar flow hood heap filters tested? |
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Are the garments made of non- shredding material? |
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What is the frequency of the garments being sterilized? |
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14.7 | STERILIZER / OVEN LOADING ROOM |
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| What is the sterilizer / oven loading room designated class? |
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What is the efficiency of filters? |
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How many air changes occur per hour? |
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Does the sterilizer meet the following criteria: |
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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? |
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What is the size of vent filter? |
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Is it capable of using thermocouples in the chamber for measuring load temperatures? |
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Is it equipped with a recording device for checking temperature and pressure? |
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Is it equipped with a vacuum pump for the removal of air from the load? |
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Is it equipped with a clean steam? |
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Does the oven meet the following criteria? |
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Is it equipped with hepa filtered air? |
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Are there 2 inter locking doors? |
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Are there recirculating fans located upstream of the HEPA filters? |
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Does it have the resistance temperature device in the return air duct for control temperature? |
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Can it maintain an empty chamber |
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+/- 20 °C for sterilization? |
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Is it equipped with a temperature recorder? |
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Can be fitted with additional temperature probes for measuring loaded materials? |
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How frequently are the sterilizer and oven calibrated and the results documented? |
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How frequently are the efficiency filters integrity tested? |
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Are the results of the testing documents? |
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Are the garments made of non sharedding material? |
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Are the garments washed and sterilized after use? |
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How frequently are they sterilized? Are the procedures validated for the sterilized/depyrogenated stoppers and components? |
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Are biological or chemical indicators used? |
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Are stoppers and components used for a given lot of product traceable via a lot number to a specific sterilizer/oven load? |
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How long can the of sterilized/depyrogenated components be stored prior use? |
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Are the processes for storage of sterilized /depyrogenated components validated? |
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Are the sterilizer and oven charts reviewed by Quality Control prior to the release of sterile products? |
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Have restrictions been established for the number of times that components may be sterilized /depyrogenated? |
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14.6 | EQUIPMENT AIRLOCK |
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| Are the air lock doors interlocked double room concept? |
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Is the airlock designated class 100,000? |
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Are there low-level air returns? What is the air flow from? |
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Does the airlock have lights? Ultraviolet Infra-Red |
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Is the airlock equipped for spray sanitization? |
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What sanitizing agent is used? |
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14.7 | WASHROOM / GOWN CHANGE ROOM |
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| Is the wash room equipped with sink and hot air hand drivers? |
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Does the wash room have lights? Ultraviolet Infra-Red |
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Does the wash room have interlocked doors? |
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Is there an airlock entry from the grown change room into the |
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Sterile rooms? |
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Is the grown change room designed as class 100,000? |
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Are garments made of non-shredding material? |
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How frequently are they sterilized? |
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What sanitization agent is used? |
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14.8 | MANUFACTURING (STERILE PRODUCTS) |
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| Does the company have adequate sterilizing, depyrogenating, sterile, filtration, processing, filling and packaging equipment available? |
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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? |
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Are sterile area air handling unit run 24/7 except for shut down due to routine maintenance to maintain sterile environment? |
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14.9 | ENVIRONMENTAL MONITORING |
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| Are laminar flow hood and HVAC system which serve the sterile operations areas validated? |
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Which department performs the validation? |
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Was the validation approved by QC/QA? |
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Was the report issued? |
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If yes, was the report forwarded to worldwide QC/QA? |
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Is there an environmental monitoring program for the aseptic batching area, sterile filling room, sterile filling line and ancillary areas? |
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Is non-viable particulate sampling performed? |
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How is viable air sampling performed? |
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How is surface sampling performed? |
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Is environmental monitoring equipment on a maintenance / calibration program? |
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At what temperature for how long are environmental monitoring samples incubated? |
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After incubation how are test results documented? |
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What nutrient media is used for environmental monitoring? |
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Are there standardized and validated autoclave loads for nutrient media used for environmental monitoring? |
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Are growth support tests performed on each lot of nutrient media that is used for environmental monitoring? |
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How is sterility verified for each lot of nutrient media that is used for environmental monitoring? |
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How is nutrient media stored prior to use? |
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14.10 | ASCEPTIC BATCHING AREA |
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| Is the area designated as class 10,000? Are there terminal Hepa filters? |
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What is the minimum of air changes per hour? |
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Is the area capable of complying with the maximum temperature (68° F) and humidity limits (50% RH)? |
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Do the laminar flow hoods provide class 100 air over the product? |
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Is all the product contact equipment in the aseptic batching area sterilizable by hot air or steam? |
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Are the walls, floors and ceilings non porous and sanitizable? |
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Are the doors self-closing without door knobs? |
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Are the light fixtures and motors totally sealed and enclosed? |
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Are the room air pressures, temperature, humidity and filter pressure drop automatically monitored, alarmed and recorded? |
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Do personnel sanitize their gloved hands? |
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Are HEPA filters and laminar flow hoods integrity tested? |
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If yes, how frequently? |
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Is equipment status labeled? |
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Are the results documented for the equipment's calibrated? |
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Are sterilization/clarification filters integrity tested and results documented |
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What is the quality of water used for equipment cleaning? |
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Are tanks, hoses etc. sterilized prior to use and are these procedures user validated? |
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Are tanks labeled during processing indicating status of product? |
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Are aseptic operations performed using laminar flow hoods? |
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Is sterile bulk sampled and tested as per testing standard requirements? |
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Are sampling and testing complete prior to or concurrent with the filling operation? |
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Is bulk held under positive pressure after final filtration / sterilization? |
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How are gases sterilized? |
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Is sterile gas filters integrity tested before and / or after use? |
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How is bulk yield determined? Are batches reprocessed? |
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If so, what are the written procedures? |
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Is rework material routinely added to batches? |
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14.11 | FILLING ROOMS |
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| Is the filling room designated as class 10,000? |
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What are the minimum air changes per hour? |
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Are environmental systems designed to run continuously? |
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Is the area capable of complying with maximum temperature (68 °F) and humidity limits (50%RH)? |
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Do this laminar flow hoods provide class 100 air over product? |
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Is the product contact equipment sterilized by hot air or steam? |
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Are the walls, floors and ceilings non- porous and sanitizable? |
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Are the doors self-closing without door knobs? |
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Are the light fixtures and motors totally sealed and enclosed? |
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Are room air pressure, temperature, humidity and filter pressure drop automatically monitored, alarmed and recorded? |
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Are the filling lines designed with laminar flow hoods to provide class 100 air at the rate of 90feet/minute at the product height? |
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Are surfaces of laminar flow hood made of stainless steel? |
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Is the filling line equipped with continuous non-hinged, non-shedding sanitizable belt or conveyor system? |
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Is the filling line equipped with automatic filling and stoppering equipment? |
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What sanitizing agent is used to sanitize gloved hands? |
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Are Hepa filters and laminar flow hoods integrity tested? If yes, how frequently? |
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How is the product delivered from aseptic batching area to the filling lines? |
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Is the sterile bulk filtered on line? |
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Is the sterile filter integrity tested before and/or after use? |
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Is the porosity and type of filter included with the batch records? |
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Are results of filter integrity test included with the batch records? |
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Is bulk held under positive pressure during filling operation? |
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How are gases sterilized? |
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Are aseptic operations performed using laminar flow hoods? |
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How is the filling figure determined? Is the fill volume checked during filling operation? |
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Are the results documented? |
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What action is taken when filling limits are exceeded? |
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Are vials flooded with nitrogen? Where are the vials capped? |
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Are rejected vials reprocessed? |
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If so what are the written procedures? Is QC/QA informed of manufacturing problems that could affect product quality? (Alert Notice System). |
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What is the quality of water used for equipment cleaning? |
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What filling equipment parts are sterilized /depyrogenated in an autoclave oven prior to use? |
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Have these processes been validated? How frequently are the filling line (including accessories) sanitized? |
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What sanitization agents are used? |
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Are the procedures validated and documented? |
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Is a filling line use record kept? |
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