MHRA guidelines for quality manufacturers of pharmaceutical formulations

The Medicines and Healthcare Products Regulatory Agency (MHRA) is a government agency in the United Kingdom. MHRA’s prime role is to regulate medicines, medical devices, and blood components for transfusion in the UK. MHRA guidelines are very important recommendations for any drug-related activity in the United Kingdom. 

It is a branch of the Department of Health and Social Care UK that executes the regulations in the healthcare sector. The agency is executed by about 1200 employees throughout the country.

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The main responsibilities of MHRA are:

• Ensuring that medicines, medical devices, and blood components for transfusion meet applicable standards of safety, quality, and efficacy
• Ensuring that the supply chain for medicines, medical devices, and blood components is safe and secure
• Promoting international standardization and harmonization to assure the effectiveness and safety of biological medicines
• Helping to educate the public and healthcare professionals about the risks and benefits of medicines, medical devices, and blood components, leading to safer and more effective use
• Supporting innovation and research and development that’s beneficial to public health
• Influencing UK, EU, and international regulatory frameworks so that they’re risk-proportionate and effective at protecting public health

MHRA Guidance for Specials Manufacturers

1. MHRA Guidelines for Quality Management

1.1 Product Quality Reviews (PQR) for MS manufacturers product Quality Reviews (PQR) for MS manufacturers

It is very necessary to prepare Product Quality Reviews (PQR)  for batches manufactured of the same product. 

1.2 Data trending

Trending should be conducted for environmental monitoring,

complaints, and deviations. Trending for environment monitoring should be conducted on monthly basis.

1.3 Capacity planning

Capacity planning means that a proper capacity plan should be maintained to ensure demand and available resources.

1.4 The basis for the formulation of an unlicensed medicine

The product manufacturing should be in accordance with the order supplied. The product formulation should be done under the supervision of qualified and trained personnel. The responsible for QC person should have qualifications ( a relevant life sciences degree) that can deal the all quality parameters properly.

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1.5 Acceptable formats for orders

The formulation of product orders should be initiated after receiving a written or email order. 

1.6 Batch Release 

When the release of a product is done, a written order must be available in mail, fax, or hard copy. 

1.7 Retrospective product release

Documentation for all quality checkups should be done before any product release.

1.8 MHRA Guidelines for Pharmacovigilance

The record of any product sold should be maintained for at least five years to investigate any quality failure found in the product. This applies to manufacturers and wholesalers. 

2. MHRA Guidelines for Personnel

There are guidelines related to personnel to work in the pharmaceutical industry and people who can handle medicines. The following guidelines are given below:

2.1 Requirements for delegated batch release.

The person that will release the batch can have a minimum of two years of experience in GMP manufacturing plant after his Science Bachelor degree. 

2.2 Independence of QA/QC and production.

The QC and QA departments in the company should be free from any influence from the production department. The in charge of QA/QC departments should be a different person than the Production Head. 

2.3 Minimum requirements for someone to be named on MS as responsible for QC

The QC in-charge should be a bachelor in Life Science Degree, the person responsible for QC should typically have a minimum of 5 years post-qualification relevant GMP experience. 

3. MHRA Guidelines for Premises and Equipment

3.1 Surface Sanitisation.

In this category proper way of sanitization, the use of disinfectant agents used for sanitization, the interval of sanitization in pharmaceutical manufacturing units is illustrated. 

3.2 Use of shared facilities.

In this guideline use of facilities for different category products manufactured in the same facility are described, precautions to be taken to avoid cross-contamination by shared machinery, equipment, or any other facility. 

3.3 MHRA Guidelines for Blood labelling.

The manner of labeling of blood samples is described in this guideline. 

3.4 Requirements for Dedicated Facilities for small scale production

In small-scale production companies, there are visible chances of cross-contamination between antibiotics, cytotoxic, and other sensitizing agents because of shared equipment used to handle them. Such cross-contamination can harm the quality of the product very badly. 

3.5 Required frequency for HEPA filter integrity checks for MS units manufacturing aseptically prepared products.

3.6 Cleaning validation for the manufacture of Specials.

In every pharmaceutical manufacturing company, proper cleaning with valid documentation is required as per GMP guidelines. The cleaning validation is very necessary to maintain. 

4 MHRA Guidelines for Documentation

4.1 Site Master File (SMF) expectations.

A pharmaceutical company must have a Site Master File which they must contain the size of the site, simple operation, and all machinery and equipment capacity.

4.2 Document retention

Documentation retention period batch documents should be retained for at least one year after expiry of 5 years after release whatever is longer.

5 MHRA Guidelines for Production

5.1 Checks required for a supplier/manufacturer of licensed products used as starting materials.

I) A licensed product with either the UK, centrally approved, or EU national license is used.

II) The product is supplied by a UK Specials manufacturer under the terms of their MS license.

III) The product is supplied by the holder of a WL under the terms of their WL license for unlicensed products.

IV) The relevant bona fide checks of the sup

5.2 Checks required for a supplier/manufacturer supplying materials with a CE mark e.g. Water for irrigation.

5.3 Checks required of a supplier/manufacturer supplying Active Substances and excipients used for the manufacture of unlicensed medicines.

5.4 Evidence required to support the assurance of GMP compliance for Active Substance.

5.5 Evidence required to support the use of excipients.

5.6 Actions to take in the event of a lack of evidence to confirm the quality of the starting materials (Active Substance or Excipient).

5.7 Use of starting materials with non-English labels.

For the non-English label of raw material supplier, it must be assured of the details explaining the raw materials. 

5.8 Requirements for TSE compliance.

All raw materials should be free from TSE risk agents. 

5.9 Expectations for the use of material reference codes in special manufacturing. 

5.10 Checks for auto-compounders.

5.11 Mix check report.

There should be a mix check report available to trace the material if any mix or change of material happens during production. 

5.12 Use of barcodes in auto-compounding.

Implementation of barcoding reduces the chances of mixing material and helps to find the right material at the time.

5.13 Checks required for reconciliation during compounding.

The system should be developed as the process of reconciliation can be performed at any time of compounding before releasing finished products. 

5.14 Key criteria for labeling systems

During the designing of a label, all GMP and drug laws-related check-ups should be performed well. 

5.15 MHRA guidelines for control of returned medicines.

A system should be developed for the reuse of returned goods to the manufacturing company. Proper SOP and validation of process need to be in place.

5.16 Requirements for the validation of unlicensed medicines.

For the manufacturing of unlicensed medicines, the principle of EU GMP Annex 15 would apply. There may be some relaxation on the basis of the product’s complexity and the size of the batch. 

MHRA guidelines for Manufacture of Sterile Medicinal Products

Aseptic manipulations

During the manufacturing of sterile medicinal products, it is very hard to maintain aseptic conditions during the process. Some aseptic manipulations found in practice by manufacturing companies must be minimized or reduced. 

The most probable aseptic manipulation takes place during the fluid path where fluid can come in contact with non-sterile surfaces or rubber stoppers. 

5.17 Design of aseptic processes in a ‘Specials’ manufacturing facility

The production of sterile products needs to be minimized aseptic manipulations and the record of every step of the manufacturing process should be documented so that the error can be traced by the inspecting officer. 

5.18 Specific requirements for the use of ampoules in ‘Specials’ manufacturing units.

In sterile medicines, ampoules should be used a single time and discarded after removal. Vial presentations should be used, it helps to maintain the closed system.

5.19 Control of pooling in a ‘Specials’ manufacturing facility.

The process refers to the bulk materials reconstitution or transfer to the pre-sterilized container without changing the concentration of the sterile bulk drug material. 

Therefore aseptic pooling of sterile bulk drug material should be minimized and avoid any contamination chances. 

5.20 Expectations for the sanitization of components and equipment being transferred into the grade A working zone

The components used for the manufacturing of products should be stored in proper airlocks and isolators to maintain the sterility of the components. The sanitization step must be carried out before transferring them to the manufacturing room. 

5.21 Factors that should be considered in developing a surface sanitization strategy.

To meet the bioburden challenge the minimum residence period should not be more than 2 minutes for components. The verification of sanitization should be carried out regularly. 

5.22 MHRA guidelines for typical sanitization agents.

Sanitization agents will be 70% alcohol or Iso Propyle Alcohol with hydrogen peroxide. 

5.23 Requirements for sessional particle monitoring for aseptic production using closed systems.

Many products require a manufacturing process aseptically that involves mandatory closed operations. In these conditions, MHRA allows risk-based assessment. (as defined in Annex 1).

6 MHRA Guideline for Quality Control sterile products manufacturing.

6.1 Points to consider when developing Environmental monitoring (EM) programme for Specials.

For the manufacturing of Sterile products environment monitoring is the key condition to maintain, following the general monitoring requirements in Annex 1 of the EU GMP guide.

6.2 Expectations of the frequency and number of products used to perform retrospective sterility testing.

A sterility test program must be adopted while manufacturing sterile products. All process variables should be considered while making the sterility test program. 

The minimum frequency of sterility tests per week no less than one. 

6.3 Requirement when only a single unit is produced.

Because of the end of session media fill simulation, the requirement of sterility testing can be offset. The testing frequency should not drop than the minimum requirement by MHRA guideline. 

7 MHRA guidance for Contract Manufacture and Analysis

No specific data is available for this topic or no specific guidelines issued. 

8 Complaints and Product Recall as per MHRA

8.1 Reporting serious complaints and recall information to DMRC for ‘Specials’

On the incident of any spurious product found DMRC should be informed immediately. No delay is allowed in such notification.

The manufacturing company should prepare the documents where has the error happened in the manufacturing process. 

9 MHRA Guidelines for Self-Inspection

MHRA has not issued specific instructions for self-inspection, a GMP compliance self-inspection process may be adopted to rectify the in-process error. 

MHRA Inspection Process for Hospital Blood Bank.

Arrangement of a date: After applying for inspection MHRA inspector will contact you for date suitability, you will be given two weeks’ time after setting an inspection date. You must have a Blood bank Manager, Consultant Haematologist, and Quality Manager

Hospital Preparation: Before the inspection date, you ensure all papers on place and can be found easily on inspection time, the laboratory should be clean and tidy. Manage all training records and check the answers you give in the compliance form. 

The inspector arrives: Ensure a proper room for the inspector to inspect the documents sitting there. 

Opening meeting: First of all introduction of all laboratory staff, Manager, quality control manager, etc, discussion for the process of inspection.

The Inspection: The inspection may include obtaining information about the laboratory and instruments, witnessing Tasks being performed in the presence of the inspector, Reviewing Documented Procedures for the testing of samples, Asking Questions – Who? What? When? Where?. After the whole process Investigating Issues – Why?

Quality management system to include:-

Personnel

Premises and Equipment

Documentation

Complaints/component recall

Self Inspection

Training records

Validation and calibration documents

Closing meeting: The closing meeting by the inspector may include the presentation of findings, the opportunity for the establishment to provide further information, acceptance of findings, and notification of next steps to be taken. 

Post-Inspection: After inspection, the laboratory can review the report furnished by the inspector and MHRA about any critical error found, major deficiency found, you have to respond within 28 days of receiving the letter from the inspector. In the response, you have to mention the corrective action you will take and the time frame. You have to do further interaction with the inspector for all steps you took for the removal of deficiency until the inspector becomes satisfied with the measure you took.

MHRA GCP Inspection Dossier checklist

The performa of required documents before MHRA inspection you must have in the company. Prepare these documents to avoid any unnecessary objections during the inspection.

Please use this checklist to ensure you have included all the relevant documentation in your GCP Inspection Dossier before submitting it to the MHRA.

Organization Name: 

GCP Inspection Dossier Requirements✔Comment (if required)1 x electronic format (as bookmarked PDF 

plus Excel spreadsheet for sections 3 and 5 

and section 2 item 3)

SECTION 1

• Item 1 Organisation Charts (Staff names present)✔Comment (if required)
• Item 2 List of clinical trial processes (i.e. a list  of all  your Policies/SOPs/Work Instructions)
• Item 3 List of all computer systems & validation status (as Excel spreadsheet) 
• Item 4 For non-commercial organizations only
• Item 5List of clinical trials (as Excel spreadsheet)
• Item 6Significant changes since the last inspection

SECTION 2

Item 1 Organization details in the UK✔Comment (if required)Primary contact details: name, job title, 

telephone number, and e-mail address Activities at the site identified  

Item 2 Organisation outside UKActivities and location at the site(s) identified 

Item 3 Delegated Tasks to Third Party Service Providers (as excel spreadsheet) 

Item 4 Contract and Agreement Preparation Regulatory Affairs Quality Systems Quality Assurance Project Management Clinical Trial Management Pharmacovigilance (including medical expertise, if applicable)Investigational Medicinal Products Data Management Statistics Clinical Trial Reporting Computer SystemsTrial Master File

Archiving Clinical Facilities Laboratories

Equipment maintenance

List of UK MHRA approved plants in India

 There are more than 100 MHRA-approved plants in India, India has 119 USFDA-approved plants in addition to 84 UK MHRA-approved plants. Some popular companies are listed below:

• Alkem Laboratory, Sena Pati Bapat Marg, Mumbai, Maharashtra, India
• RUSAN PHARMA LTD, 58-D, Govt. Industrial Estate, Charkop, Kandivali West, Mumbai, Maharashtra
• Flamingo Pharma Ltd., Corporate Park, Chembur, Mumbai, Maharashtra, India
• Milan Laboratories (India) Pvt. Ltd., A-5, Megh Malhar, Gavand Path, Naupada, Thane, Maharashtra, India.
• Ind-Swift Ltd., 714, Modi Tower, 98, Nehru Place, New Delhi, Delhi, India
• KLINTOZ Pharmaceuticals Pvt. Ltd., 405, Madhuban Building, 55 Nehru Place, New Delhi, Delhi, India
• Indoco remedies ltd, 55Address166, Cst Road, Santacruz – East, Kalina, Mumbai, Maharashtra, India.
• Health Secure India Pvt. Ltd, C-10, Midc, Taloja, Maharashtra, India
• Torrent Pharma, manufacturing Facility at Pithampur, Madhya Pradesh
• Qualtra Pharmaceuticals, Unit 23, Plot No 5, Pitampura New Delhi-India
• Claris Lifesciences, located in Ahmedabad, Gujarat, India.
• Sun Pharmaceuticals, Baddi Himachal Pradesh.
• Svizera Labs Pvt Ltd., TTC Industrial Area Navi Mumbai-India.

MHRA-GMP Audit Checklist For Drug Manufacturers

MHRA inspections usually are to check the cGMP compliance status in the manufacturing unit. MHRA inspector audits various aspects followed by the manufacturing facility that ensure the output of quality products, these aspects include all recommended parameters by cGMP. World-famous website  ISPE (Connecting Pharmaceutical Knowledge) provides an outline for preparation for MHRA-led GMP audit. The GMP audit checklist helps to find any error present in the system before the audit. You can see it here:- 

GMP Audit Checklist QuestionInstructions/QuestionsNote any exceptions and comments in the notebook Yes/No/NA1.0General Controls  Does the facility and its many departments (organizational units) operate in a state of control as defined by the GMP regulations? 1.1 Organizational & Management Responsibilities 1.101 Does this facility/business unit operate under a facility or corporate quality policy? 1.102§211.22(a) Does a Quality Assurance unit (department) exist as a separate organizational entity? 1.103§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? 1.104§211.22 Does the QA department or unit routinely review production records to ensure that procedures were followed and properly documented? 1.105§211.22(b) Are adequate laboratory space, equipment, and qualified personnel available for required testing? 1.106If 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? 1.107Date of last inspection:____________________ 1.108§211.22(c) Are all QA procedures in writing? 1.109§211.22(c) Are all QA responsibilities in writing? 1.110Are all written QA procedures current and approved? (Review log of procedures) 1.111Are the procedures followed? (Examine records to ensure consistent record-keeping that adequately documents testing.) 1.112§211.25 Are QA supervisory personnel qualified by way of training and experience? 1.113§211.25 Are other QA personnel, e.g., chemists, analysts, laboratory technicians) qualified by way of training and experience? 1.201§211.22(a) Does the QA unit have a person or department specifically charged with the responsibility of designing, revising, and obtaining approval for production and testing procedures, forms, and records? 1.202§211.22(d) Does a written SOP, which identifies how the form is to be completed and who signs and countersigns, exist for each record or form? 1.203§211.165(a)(b)(c) Is the production batch record and release test results reviewed for accuracy and completeness before a batch/lot of finished product is released? 1.3Employee Orientation, Quality Awareness, and Job Training 1.301Circle the types of orientation provided to each new employee: (1) Company brochure (2) Literature describing GMP regulations and stressing importance of following instructions. (3) On-the-job training for each function to be performed (before the employee is allowed to perform such tasks). (4) Other: enter in notebook. 1.302§211.25(a) Does each employee receive retraining on an SOP (procedures) if critical changes have been made in the procedure? 1.303Indicate how on-going, periodic GMP training is accomplished. 1.304§211.25 is all training documented in writing that indicates the date of the training, the type of training, and the signature of both the employee and the trainer? 1.305§211.25 Are training records readily retrievable in a manner that enables one to determine what training an employee has received, which employees have been trained on a particular procedure, or have attended a particular training program? 1.306Are GMP trainers qualified through experience and training? 1.307§211.25(a) Are supervisory personnel instructed to prohibit any employee who, because of any physical condition (as determined by medical examination or supervisory observation) that may adversely affect the safety or quality of drug products, from coming into direct contact with any drug component or immediate containers for finished product? 1.308§211.28(d) Are employees required to report to supervisory personnel any health or physical condition that may have an adverse effect on drug product safety and purity? 1.309§211.25(a) Are temporary employees given the same orientation as permanent employees? 1.310§211.34 Are consultants, who are hired to advise on any aspect of manufacture, processing, packing or holding, of approval for release of drug products, asked to provide evidence of their education, training, and experience? 1.311§211.34 Are written records maintained stating the name, address, qualifications, and date of service for any consultants and the type of service they provide? 1.4Plant Safety and Security 1.401Does this facility have a facility or corporate safety program? 1.402Are safety procedures written? 1.403Are safety procedures current? 1.404Do employees receive safety orientation before working in the plant area? 1.405Is safety training documented in a readily retrievable manner that states the name of the employee, the type of training, the date of the training, and the name of the trainer and the signature of the trainer and the participant? 1.406Does this facility have a formal, written security policy? 1.407Is access to the facility restricted? 1.408Describe how entry is monitored/restricted: 1.409Is a security person available 24 hours per day? 1.5Internal Quality/GMP Audit Program 1.501Does this business unit/facility have a written quality policy? 1.502Is a copy of this quality policy furnished to all employees? 1.503If “yes” to above, when provided? __________________ 1.504Is training provided in quality improvement? 1.505Does a formal auditing function exist in the Quality Assurance department? 1.506Does a written SOP specify who shall conduct audits and qualifications (education, training, and experience) for those who conduct audits? 1.507Does a written SOP specify the scope and frequency of audits and how such audits are to be documented? 1.508Does a written SOP specify the distribution of the audit report? 1.6Quality Cost Program 1.601Does this facility have a periodic and formal review of the cost of quality? 1.602Does this facility have the ability, through personnel, software, and accounting records, to identify and capture quality costs? 1.603Does this facility make a conscious effort to reduce quality costs? gmp-audit.

QuestionInstructions/QuestionsNote any exceptions and comments in the notebookYes/No/NA2.0Design Control   Not directly related to 21 CFR Parts 210 and 211 gmp-audit.

QuestionInstructions/QuestionsNote any exceptions and comments in the notebookYes/No/NA3.0Facility Control 3.1Facility 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? 3.103Does the layout and organization of the facility prevent contamination? 3.2Environmental Control Program 3.201The facility is NOT situated in a location that potentially subjects workers or product to particulate matter, fumes, or infestations? 3.202Are 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? 3.207Are 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!) 3.3Facility 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? 3.303Is this facility maintained in a clean and sanitary condition? 3.304Does this facility have written procedures that describe in sufficient detail the cleaning schedule, methods, equipment and material? 3.305Does 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?) 3.4Outside 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? gmp-audit-checklist..

QuestionInstructions/QuestionsNote any exceptions and comments in notebookYes/No/NA4.0Equipment Control 4.1Equipment Design and Placement 4.101§211.63 Is all equipment used to manufacture, process or hold a drug product of appropriate design and size for its intended use? 4.102Are the following pieces of equipment suitable for their purpose? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify). 4.103Are the following pieces of equipment suitable in their size/capacity? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify). 4.104Are the following pieces of equipment suitable in their design? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify). 4.105Are the locations in the facility of the following pieces of equipment acceptable? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify). 4.106Are the following pieces of equipment properly installed? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify). 4.107Is there adequate space for the following pieces of equipment? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify). 4.108§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? 4.109§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? 4.110§211.72 Fiber-releasing filters are NOT used in the production of injectable products? 4.111§ 211.72 Asbestos filters are NOT used in the production of products? 4.112Is each idle piece of equipment clearly marked “needs cleaning” or “cleaned; ready for service”? 4.113Is equipment cleaned promptly after use? 4.114Is idle equipment stored in a designated area? 4.115§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? 4.116Do cleaning instructions include disassembly and drainage procedure, if required, to ensure that no cleaning solution or rinse remains in the equipment? 4.117Does the cleaning procedure or startup procedure ensure that the equipment is systematically and thoroughly cleaned? 4.2Equipment Identification 4.201§211.105 Are all pieces of equipment clearly identified with easily visible markings? 4.202§211.105(b) Are all pieces of equipment also marked with an identification number that corresponds with an entry in an equipment log? 4.203Does each piece of equipment have written instructions for maintenance that includes a schedule for maintenance? 4.204Is the maintenance log for each piece of equipment kept on or near the equipment? 4.3Equipment Maintenance & Cleaning 4.301§211.67(b) Are written procedures established for the cleaning and maintenance of equipment and utensils? 4.302Are these procedures followed? 4.303§211.67(b)(1) Does a written procedure assign responsibility for the cleaning and maintenance of equipment? 4.304§211.67(b)(2) Has a written schedule been established and is it followed for the maintenance and cleaning of equipment? 4.305Has the cleaning procedure been properly validated? 4.306§211.67(b)(2) If appropriate, is the equipment sanitized using a procedure written for this task? 4.307§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? 4.308§211.67(b)(3) Does the procedure specify the removal or obliteration of production batch information from each piece of equipment during its cleaning? 4.309Is equipment cleaned promptly after use? 4.310Is clean equipment clearly identified as “clean” with a cleaning date shown on the equipment? 4.311§211.67(b)(5)  Is clean equipment adequately protected against contamination prior to use? 4.312§211.67(b)  Is equipment inspected immediately prior to use? 4.313§211.67(c)  Are written records maintained on equipment cleaning, sanitizing and maintenance on or near each piece of equipment? 4.4Measurement Equipment Calibration Program 4.401§211.68(a)  Does the facility have approved written procedures for checking and calibration of each piece of measurement equipment?  (Verify procedure and log for each piece of equipment and note exceptions in notebook with cross reference.) 4.402§211.68(a)   Are records of calibration checks and inspections maintained in a readily retrievable manner? 4.5Equipment Qualification Program 4.501§211.63 Verify that all pieces of equipment used in production, packaging, and quality assurance are capable of producing valid results. 4.502§211.68(a)  When computers are used to automate production or quality testing, have the computer and software been validated? 4.503Have on-site tests of successive production runs or tests been used to qualify equipment? 4.504Were tests repeated a sufficient number of times to ensure reliable results? 4.505§211.63  Is each piece of equipment identified to its minimum and maximum capacities and minimum and maximum operating speeds for valid results? 4.506Have performance characteristics been identified for each piece of equipment?  (May be provided by the manufacturer, but must be verified under typical operations conditions.) 4.507Have operating limits and tolerances for performance been established from performance characteristics? 

QuestionInstructions/QuestionsNote any exceptions and comments in notebookYes/No/NA5.0Material/Component Control 5.1Material/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. 5.101Has 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.) 5.2Material/Component Receipt, Inspection, Sampling, a