This GMP audit checklist is intended to aid in the systematic audit of a facility that manufactures drug components or finished products. The adequacy of any procedures is subject to the interpretation of the auditor. Therefore, ISPE and the GMP Institute accept no liability for any subsequent regulatory observations or actions stemming from the use of this audit checklist.
Before starting an on-site audit, plan the audit. Review past audits, note indications of possible problem areas and items, if any, that were identified for corrective action in a previous audit. If you are not already familiar with this facility, learn the type of product produced here and how it is organized by personnel and function. What does your "customer", i.e., your superior or senior facility management, expect to learn from this audit?
1.1
Organizational & Management Responsibilities
Does this facility/business unit operate under a facility or corporate quality policy?
§211.22(a) Does a Quality Assurance unit (department) exist as a separate organizational entity?
§211.22(a) Does the Quality Assurance unit alone have both the authority and responsibility to approve or reject all components, drug product containers and closures, in-process materials, packaging materials, labeling and drug products?
§211.22 Does the QA department or unit routinely review production records to ensure that procedures were followed and properly documented?
§211.22(b) Are adequate laboratory space, equipment, and qualified personnel available for required testing?
If any portion of testing is performed by a contractor, has the Quality Assurance unit inspected the contractor's site and verified that the laboratory space, equipment, qualified personnel and procedures are adequate?
Date of last inspection:____________________
§211.22(c) Are all QA procedures in writing?
§211.22(c) Are all QA responsibilities in writing?
Are all written QA procedures current and approved? (Review log of procedures)
Are the procedures followed? (Examine records to ensure consistent record-keeping that adequately documents testing.)
§211.25 Are QA supervisory personnel qualified by way of training and experience?
§211.25 Are other QA personnel, e.g., chemists, analysts, laboratory technicians) qualified by way of training and experience?
| Question | Instructions/Questions Note any exceptions and comments in notebook | Yes/No/NA |
|---|---|---|
| 2.0 | Design Control | |
| Not directly related to 21 CFR Parts 210 and 211 |
| Question | Instructions/Questions Note any exceptions and comments in notebook | Yes/No/NA |
|---|---|---|
| 3.0 | Facility Control | |
| 3.1 | Facility Design and Layout | |
| 3.101 | §211.42(a) Are all parts of the facility constructed in a way that makes them suitable for the manufacture, testing, and holding of drug products? | |
| 3.102 | §211.42(b) Is there sufficient space in the facility for the type of work and typical volume of production? | |
| 3.103 | Does the layout and organization of the facility prevent contamination? | |
| 3.2 | Environmental Control Program | |
| 3.201 | The facility is NOT situated in a location that potentially subjects workers or product to particulate matter, fumes, or infestations? | |
| 3.202 | Are grounds free of standing water? | |
| 3.203 | §211.44 Is lighting adequate in all areas? | |
| 3.204 | §211.46 Is adequate ventilation provided? | |
| 3.205 | §211.46 Is control of air pressure, dust, humidity and temperature adequate for the manufacture, processing, storage or testing of drug products? | |
| 3.206 | §211.46 If air filters are used, is there a written procedure specifying the frequency of inspection and replacement? | |
| 3.207 | Are drains and routine cleaning procedures sufficient to prevent standing water inside the facility? | |
| 3.208 | §211.42(d) Does the facility have separate air handling systems, if required, to prevent contamination? (MANDATORY IF PENICILLIN IS PRESENT!) | |
| 3.3 | Facility Maintenance and Good Housekeeping Program | |
| 3.301 | §211.56(a) Is this facility free from infestation by rodents, birds, insects and vermin? | |
| 3.302 | §211.56(c) Does this facility have written procedures for the safe use of suitable, (e.g. those that are properly registered) rodenticides, insecticides, fungicides, and fumigating agents? | |
| 3.303 | Is this facility maintained in a clean and sanitary condition? | |
| 3.304 | Does this facility have written procedures that describe in sufficient detail the cleaning schedule, methods, equipment and material? | |
| 3.305 | Does this facility have written procedures for the safe and correct use of cleaning and sanitizing agents? | |
| 3.306 | §211.58 Are all parts of the facility maintained in a good state of repair? | |
| 3.307 | §211.52 Is sewage, trash and other refuse disposed of in a safe and sanitary manner (and with sufficient frequency?) | |
| 3.4 | Outside Contractor Control Program | |
| 3.401 | §211.56(d) Are contractors and temporary employees required to perform their work under sanitary conditions? | |
| 3.402 | §163 Are contractors qualified by experience or training to perform tasks that may influence the production, packaging, or holding of drug products? |
4.0
Equipment Control
4.1
Equipment Design and Placement
§211.63 Is all equipment used to manufacture, process or hold a drug product of appropriate design and size for its intended use?
Are the following pieces of equipment suitable for their purpose? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify).
Are the following pieces of equipment suitable in their size/capacity? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify).
Are the following pieces of equipment suitable in their design? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify).
Are the locations in the facility of the following pieces of equipment acceptable? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify).
Are the following pieces of equipment properly installed? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify).
Is there adequate space for the following pieces of equipment? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify).
§211.65(a) Are machine surfaces that contact materials or finished goods non-reactive, non-absorptive, and non-additive so as not to affect the product?
§211.65(b) Are design and operating precautions taken to ensure that lubricants or coolants or other operating substances do NOT come into contact with drug components or finished product?
§211.72 Fiber-releasing filters are NOT used in the production of injectable products?
§ 211.72 Asbestos filters are NOT used in the production of products?
Is each idle piece of equipment clearly marked "needs cleaning" or "cleaned; ready for service"?
Is equipment cleaned promptly after use?
Is idle equipment stored in a designated area?
§211.67(a)(b) Are written procedures available for each piece of equipment used in the manufacturing, processing or holding of components, in-process material or finished product?
Do cleaning instructions include disassembly and drainage procedure, if required, to ensure that no cleaning solution or rinse remains in the equipment?
Does the cleaning procedure or startup procedure ensure that the equipment is systematically and thoroughly cleaned?
4.2
Equipment Identification
§211.105 Are all pieces of equipment clearly identified with easily visible markings?
§211.105(b) Are all pieces of equipment also marked with an identification number that corresponds with an entry in an equipment log?
Does each piece of equipment have written instructions for maintenance that includes a schedule for maintenance?
Is the maintenance log for each piece of equipment kept on or near the equipment?
4.3
Equipment Maintenance & Cleaning
§211.67(b) Are written procedures established for the cleaning and maintenance of equipment and utensils?
Are these procedures followed?
§211.67(b)(1) Does a written procedure assign responsibility for the cleaning and maintenance of equipment?
§211.67(b)(2) Has a written schedule been established and is it followed for the maintenance and cleaning of equipment?
Has the cleaning procedure been properly validated?
§211.67(b)(2) If appropriate, is the equipment sanitized using a procedure written for this task?
§211.67(b)(3) Has a sufficiently detailed cleaning and maintenance procedure been written for each different piece of equipment to identify any necessary disassembly and reassembly required to provide cleaning and maintenance?
§211.67(b)(3) Does the procedure specify the removal or obliteration of production batch information from each piece of equipment during its cleaning?
| Question | Instructions/Questions Note any exceptions and comments in notebook | Yes/No/NA |
|---|---|---|
| 5.0 | Material/Component Control | |
| 5.1 | Material/Component Specification and Purchasing Control | |
| Although purchasing is not specifically addressed in the current GMP regulation, incumbent upon user of components and materials to ensure quality of product, material or component. | ||
| 5.101 | Has each supplier/vendor of material or component been inspected/audited for proper manufacturing controls? (Review suppliers and audits and enter names, material supplied, and date last audited in notebook.) | |
| 5.2 | Material/Component Receipt, Inspection, Sampling, and Laboratory Testing | |
| 5.201 | §211.80(a) Does the facility have current written procedures for acceptance/rejections of drug products, containers, closures, labeling and packaging materials? (List selected materials and components in notebook and verify procedures.) | |
| 5.202 | §211.80(d) Is each lot within each shipment of material or components assigned a distinctive code so material or component can be traced through manufacturing and distribution? | |
| 5.203 | §211.82(a) Does inspection start with visual examination of each shipping container for appropriate labeling, signs of damage, or contamination? | |
| 5.204 | §211.82(b) Is the number of representative samples taken from a container or lot based on statistical criteria and experience with each type of material or component? | |
| 5.205 | §211.160(b) Is the sampling technique written and followed for each type of sample collected? | |
| 5.206 | Is the quantity of sample collected sufficient for analysis and reserve in case retesting or verification is required? | |
| Verify that the following steps are included in written procedures unless more specific procedures are followed: | ||
| 5.207 | §211.84(c)(2) Containers are cleaned before samples are removed. | |
| 5.208 | §211.84(c)(4) Stratified samples are not composited for analysis. | |
| 5.209 | §211.84(c)(5) Containers from which samples have been taken are so marked indicating date and approximate amount taken. | |
| 5.210 | Each sample container is clearly identified by material or component name, lot number, date sample taken, name of person taking sample, and original container identification. | |
| 5.211 | §211.84(d)(1)(2) At least one test is conducted to confirm the identity of a raw material (bulk chemical or pharmaceutical) when a Certificate of Analysis is provided by supplier and accepted by QA. | |
| 5.212 | If a Certificate of Analysis is not accepted for a lot of material, then additional testing is conducted by a written protocol to determine suitability for purpose. | |
| 5.213 | §211.84(d)(6) Microbiological testing is conducted where appropriate. | |
| 5.3 | Material Component Storage and Handling | |
| (Verify that materials and components are stored and handled in a way that prevents contamination, mixups, and errors.) | ||
| 5.301 | §211.42(b) Are incoming material and components quarantined until approved for use? | |
| 5.302 | Are all materials handled in such a way to prevent contamination? | |
| 5.303 | Are all materials stored off the floor? | |
| 5.304 | Are materials spaced to allow for cleaning and inspection? | |
| 5.305 | §211.122(d) Are labels for different products, strengths, dosage forms, etc., stored separately with suitable identification? | |
| 5.306 | Is label storage area limited to authorized personnel? | |
| 5.307 | §211.89 Are rejected components, material, and containers quarantined and clearly marked to prevent their use? | |
| 5.4 | Inventory Control Program | |
| 5.401 | §211.142 Are inventory control procedures written? | |
| 5.402 | Does the program identify destruction dates for obsolete or out-dated materials, components, and packaging materials? | |
| 5.403 | §211.150(a) Is stock rotated to ensure that the oldest approved product or material is used first? | |
| 5.404 | §211.184(e) Is destruction of materials documented in a way that clearly identifies the material destroyed and the date on which destruction took place? | |
| 5.5 | Vendor (Supplier) Control Program | |
| 5.501 | Are vendors periodically inspected according to a written procedure? | |
| 5.502 | Is the procedure for confirming vendor test results written and followed? |
| Question | Instructions/Questions Note any exceptions and comments in notebook | Yes/No/NA |
|---|---|---|
| 6.0 | Operational Control | |
| 6.1 | Material/Component/Label Verification, Storage, and Handling | |
| 6.101 | §211.87 Do written procedures identify storage time beyond which components, containers, and closures must be reexamined before use? | |
| 6.102 | §211.87 Is release of retested material clearly identified for use? | |
| 6.103 | Are retesting information supplements originally obtained? | |
| 6.104 | Do written procedures identify steps in the dispensing of material for production? | |
| 6.105 | Do these procedures include (1) release by QC, (2)Documentation of correct weight or measure, and (3) Proper identification of containers? | |
| 6.106 | Does a second person observe weighing/measuring/dispensing and verify accuracy with a second signature? | |
| 6.107 | §211.101(c) Is the addition of each component documented by the person adding the material during manufacturing? | |
| 6.108 | §211.101(d) Does a second person observe each addition of material and document verification with a second signature? | |
| 6.109 | §211.125(a) Does a written procedure specify who is authorized to issue labels? | |
| 6.110 | §211.125(a) Does a written procedure specify how labels are issued, used, reconciled with production, returned when unused, and the specific steps for evaluation of any discrepancies? | |
| 6.111 | §211.125(d) Do written procedures call for destruction of excess labeling on which lot or control numbers have been stamped or imprinted? | |
| 6.2 | Equipment/Line/Area Cleaning, Preparation, and Clearance | |
| 6.201 | §211.67(b)(5) Do written procedures detail how equipment is to be checked immediately prior to use for cleanliness, removal of any labels and labeling from prior print operations? | |
| 6.202 | §211.67(b)(3) Do written procedures detail any disconnection and reassembly required to verify readiness for use? | |
| 6.3 | Operational Process Validation and Production Change Order Control | |
| 6.301 | Have production procedures been validated? (Review selected procedures for validation documentation. Adequate?) | |
| 6.302 | §211.100(a) Does the process control address all issues to ensure identity, strength, quality and purity of product? | |
| 6.303 | §§211.101(a) Does the procedure include formulation that is written to yield not less than 100% of established amount of active ingredients? | |
| 6.304 | §211.101(c) Are all weighing and measuring preformed by one qualified person and observed by a second person? | |
| 6.305 | §211.101(d) Have records indicated preceding policy been followed by presence of two signatures? | |
| 6.306 | §211.103 Are actual yields calculated at the conclusion of appropriate phases of the operation and at the end of the process? | |
| 6.307 | §211.103 Are calculations performed by one person? Is there independent verification by a second person? | |
| 6.4 | In-Process Inspection, Sampling, and Laboratory Control | |
| 6.401 | §211.110(a) Are written procedures established to monitor output and validate the performance of manufacturing procedures that may cause variability in characteristics of in-process materials and finished drug products? | |
| 6.402 | §211.110(c) Are in-process materials tested at appropriate phases for identity, strength, quality, purity and are they approved or rejected by Quality Control? | |
| 6.403 | §211.160(b) Are there laboratory controls including sampling and testing procedures to assure conformance of components, containers, closures, in-process materials, and finished product specifications? | |
| 6.5 | Reprocessing/Disposition of Materials | |
| 6.501 | §211.115(a) Do written procedures identify steps for reprocessing batches? | |
| 6.502 | §211.115(b) Are quality control review and approval required for any and all reprocessing of material? | |
| 6.503 | Does testing confirm that reprocessed batches conform to established specification? | |
| 6.504 | Does a written procedure outline steps required to reprocess returned drug products (if it can be determined that such products have not been subjected to improper storage conditions?) | |
| 6.505 | Does Quality Control review such reprocessed returned goods and test such material for conformance to specifications before releasing such material for resale? |
| Question | Instructions/Questions Note any exceptions and comments in notebook | Yes/No/NA |
|---|---|---|
| 7.0 | Finished Product Control | |
| 7.1 | Finished Product Verification, Storage, and Handling | |
| 7.101 | §211.30 Do written procedures indicate how and who verifies that correct containers and packages are used for finished product during the finishing operation? | |
| 7.102 | §211.134(a) In addition, do written procedures require that representative sample of units be visually examined upon completion of packaging to verify correct labeling? | |
| 7.103 | §211.137(a) Are expiration dates stamped or imprinted on labels? | |
| 7.104 | §211.137(b) Are expiration dates related to any storage conditions stated on the label? | |
| 7.105 | §211.142(a) Are all finished products held in quarantine until QC has completed its testing and releases product on a batch to batch basis for sale? | |
| 7.106 | §211.142(o) Is finished product stored under appropriate conditions of temperature, humidity, light, etc. | |
| 7.2 | Finished Product Inspection, Sampling, Testing, and Release for Distribution | |
| 7.201 | §211.166 Has the formulation for each product been tested for stability based on a written protocol? (Containers must duplicate those used in final product packaging.) | |
| 7.202 | §211.166 Are written sampling and testing procedures and acceptance criteria available for each product to ensure conformance to finished product specifications? | |
| 7.203 | §211.170(a) Is a quantity of samples equal to at least twice the quantity needed for finished product release testing maintained as a reserve sample? | |
| 7.204 | §211.167(a) Are sterility and pyrogen testing performed as required? | |
| 7.205 | §211.167(b) Are specific tests for foreign particles or abrasives included for any ophthalmic ointments? | |
| 7.206 | §211.167(c) Do controlled release or sustained release products include tests to determine conformance to release time specification? | |
| 7.3 | Distribution Controls | |
| 7.301 | §211.150(a) Does a written procedure manage stocks to ensure that oldest approved product is sold first? | |
| 7.302 | §211.150(a) Are deviations to the policy above documented? | |
| 7.303 | §211.150(a) Does a written procedure identify the steps required if a product recall is necessary? | |
| 7.304 | Is the recall policy current and adequate? | |
| 7.4 | Marketing Controls | |
| 7.401 | The current regulation does not address marketing controls per se except that all finished products must meet their specifications. | |
| 7.5 | Complaint Handling and Customer Satisfaction Program | |
| 7.501 | §211.198(a) Are complaints, whether received in oral or written form, documented in writing and retained in a designated file? | |
| 7.502 | §211.198(a) Are complaints reviewed on a timely basis by the Quality Control Unit? | |
| 7.503 | §211.198(b)(1) Is the action taken in response to each complaint documented? | |
| 7.504 | §211.198(b)(3) Are decisions not to investigate a complaint also documented and the name of the responsible person documented? | |
| 7.505 | §211.198(b)(2) Are complaint investigations documented and do they include investigation steps, findings, and follow-up steps, if required? Are dates included for each entry? |