Pure Steam— is also sometimes referred to as “clean steam”. It is used where the steam or its condensate would directly contact official articles or article-contact surfaces, such as during their preparation, sterilization, or cleaning where no subsequent processing step is used to remove any impurity residues. These Pure Steam applications include but are not limited to porous load sterilization processes, product or cleaning solutions heated by direct steam injection, or humidification of processes where steam injection is used to control the humidity inside processing vessels where the official articles or their in-process forms are exposed. The primary intent of using this quality of steam is to ensure that official articles or article-contact surfaces exposed to it are not contaminated by residues within the steam. The minimal quality of source water for the production of Pure Steam is Drinking Water whose attributes are prescribed by the U.S. EPA, EU, Japan, or WHO, and which has been suitably treated. The water is then vaporized with suitable mist elimination, and distributed under pressure. The sources of undesirable contaminants within Pure Steam could arise from entrained source water droplets, anticorrosion steam additives, or residues from the steam production and distribution system itself. The chemical tests in the Pure Steam monograph should detect most of the contaminants that could arise from these sources. If an official article is exposed to Pure Steam and it is intended for parenteral use or other applications where the pyrogenic content must be controlled, the Pure Steam must additionally meet the specification for Bacterial Endotoxins Test These purity attributes are measured in the condensate of the article, rather than the article itself. This, of course, imparts great importance to the cleanliness of the process for Pure Steam condensate generation and collection, because it must not adversely impact the quality of the resulting condensed fluid. Other steam attributes not detailed in the monograph, in particular, the presence of even small quantities of noncondensable gases or the existence of a superheated or dry state, may also be important for applications such as sterilization. The large release of energy (latent heat of condensation) as water changes from the gaseous to the liquid state is the key to steam’s sterilization efficacy and its efficiency, in general, as a heat transfer agent. If this phase change (condensation) is not allowed to happen because the steam is extremely hot and in a persistent superheated, dry state, then its usefulness could be seriously compromised. Noncondensable gases in steam tend to stratify or collect in certain areas of a steam sterilization chamber or its load. These surfaces would thereby be at least partially insulated from the steam condensation phenomenon, preventing them from experiencing the full energy of the sterilizing conditions. Therefore, control of these kinds of steam attributes, in addition to its chemical purity, may also be important for certain Pure Steam applications. However, because these additional attributes are use-specific, they are not mentioned in the Pure Steam monograph. Note that lower-purity “plant steam” may be used in the following applications: 1) for steam sterilization of nonproduct-contact nonporous loads, 2) for general cleaning of nonproduct-contact equipment, 3) as a nonproduct-contact heat-exchange medium, and 4) in all compatible applications involved in bulk pharmaceutical chemical and API manufacture. Finally, because Pure Steam is lethal to microbes, monitoring of microbial control within a steam system is unnecessary, as is microbial analysis of the steam condensate.

Water for Hemodialysis— is used for hemodialysis applications, primarily the dilution of hemodialysis concentrate solutions. It is produced and used on-site and is made from EPA Drinking Water that has been further purified to reduce chemical and microbiological components. It may be packaged and stored in unreactive containers that preclude bacterial entry. The term “unreactive containers” implies that the container, especially its water contact surfaces, is not changed in any way by the water, such as by leaching of container-related compounds into the water or by any chemical reaction or corrosion caused by the water. The water contains no added antimicrobials and is not intended for injection. Its attributes include specifications for water conductivity, total organic carbon (or oxidizable substances), microbial limits, and bacterial endotoxins. The water conductivity and total organic carbon attributes are identical to those established for Purified Water and Water for Injection; however, instead of total organic carbon (TOC), the organic content may alternatively be measured by the test for Oxidizable Substances. The microbial limits attribute for this water is unique among the “bulk” water monographs, but is justified on the basis of this water's specific application that has microbial content requirements related to its safe use. The bacterial endotoxins attribute is likewise established at a level related to its safe use.

Water for Injection— is used as an excipient in the production of parenteral and other preparations where product endotoxin content must be controlled, and in other pharmaceutical applications, such as cleaning of certain equipment and parenteral product-contact components. The minimum quality of source or feed water for the generation of Water for Injection is Drinking Water as defined by the U.S. Environmental Protection Agency (EPA), EU, Japan, or WHO. This source water may be pretreated to render it suitable for subsequent distillation (or whatever other validated process is used according to the monograph). The finished water must meet all of the chemical requirements specified in the monograph as well as an additional bacterial endotoxin specification. Because endotoxins are produced by the kinds of microorganisms that are prone to inhabit water, the equipment and procedures used by the system to purify, store, and distribute Water for Injection must be designed to minimize or prevent microbial contamination as well as remove incoming endotoxins from the starting water. Water for Injection systems must be validated to reliably and consistently produce and distribute this quality of water. The Water for Injection monograph also allows bulk packaging for commercial use. In contrast to Sterile Water for Injection, bulk packaged Water for Injection is not required to be sterile. However, to preclude significant changes in its microbial and endotoxins content during storage, this form of Water for Injection should be prepared and stored in a fashion that limits microbial growth and/or is simply used in a timely fashion before microbial proliferation renders it unsuitable for its intended use. Also depending on the material used for packaging, there could be extractable compounds leaching into the water from the packaging. Although this article is required to meet the same chemical purity limits as the bulk water, packaging extractables will render the packaged water less pure than the bulk water. The nature of these impurities may even render the water an inappropriate choice for some applications. It is the user's responsibility to ensure fitness for use of this packaged article when used in manufacturing, clinical, or analytical applications where the purer bulk form of the water is indicated.

Purified Water [Note—For microbiological guidance, see USP general information chapter Water for Pharmaceutical Purposes 1231. ] H2O 18.02 DEFINITION Purified Water is water obtained by a suitable process. It is prepared from water complying with the U. S. Environmental Protection Agency National Primary Drinking Water Regulations or with the drinking water regulations of the European Union or of Japan, or with the World Health Organization's Guidelines for Drinking Water Quality. It contains no added substance. [Note—Purified Water whether it is available in bulk or packaged forms, is intended for use as an ingredient of official preparations and in tests and assays unless otherwise specified Where used for sterile dosage forms, other than for parenteral administration, process the article to meet the requirements under Sterility Tests 71, or first render the Purified Water sterile and thereafter protect it from microbial contamination. Do not use Purified Water in preparations intended for parenteral administration. For such purposes use Water for Injection, Bacteriostatic Water for Injection, or Sterile Water for Injection. In addition to the Specific Tests, Purified Water that is packaged for commercial use elsewhere meets the additional requirements for Packaging and Storage and Labeling as indicated under Additional Requirements. ] SPECIFIC TESTS [Note—Required for bulk and packaged forms of Purified Water ] • Total Organic Carbon 643: Meets the requirements • Water Conductivity, Bulk Water 645: Meets the requirements ADDITIONAL REQUIREMENTS [Note—Required for packaged forms of Purified Water ] • Packaging and Storage: Where packaged, preserve in unreactive storage containers that are designed to prevent microbial entry. • Labeling: Where packaged, label it to indicate the method of preparation and that it is not intended for parenteral administration. • Reference Standards 1,4-Benzoquinone Sucrose

Purified Water— is used as an excipient in the production of nonparenteral preparations and in other pharmaceutical applications, such as cleaning of certain equipment and nonparenteral product-contact components. Unless otherwise specified, Purified Water is also to be used for all tests and assays for which water is indicated. Purified Water must meet the requirements for ionic and organic chemical purity and must be protected from microbial contamination. The minimal quality of source or feed water for the production of Purified Water is Drinking Water. This source water may be purified using unit operations that include deionization, distillation, ion exchange, reverse osmosis, filtration, or other suitable purification procedures. Purified water systems must be validated to reliably and consistently produce and distribute water of acceptable chemical and microbiological quality. Purified water systems that function under ambient conditions are particularly susceptible to the establishment of tenacious biofilms of microorganisms, which can be the source of undesirable levels of viable microorganisms or endotoxins in the effluent water. These systems require frequent sanitization and microbiological monitoring to ensure water of appropriate microbiological quality at the points of use. The Purified Water monograph (USP) also allows bulk packaging for commercial use elsewhere. In contrast to Sterile Purified Water, bulk packaged Purified Water is not required to be sterile. Because there is potential for microbial contamination and other quality changes in this bulk packaged non-sterile water, this form of Purified Water should be prepared and stored in a fashion that limits microbial growth and/or is simply used in a timely fashion before microbial proliferation renders it unsuitable for its intended use. Also depending on the material used for packaging, there could be extractable compounds leaching into the water from the packaging. Although this article is required to meet the same chemical purity limits as the bulk water, packaging extractables will render the packaged water less pure than the bulk water. The nature of these impurities may even render the water an inappropriate choice for some applications. It is the user's responsibility to ensure fitness for use of this packaged article when used in manufacturing, clinical, or analytical applications where the pure bulk form of the water is indicated.

WATERS USED FOR PHARMACEUTICAL MANUFACTURING AND TESTING PURPOSES Bulk Monographed Waters and Steam Purified Water Water for Injection Water for Hemodialysis Pure Steam Sterile Monographed Waters Sterile Purified Water Sterile Water for Injection Bacteriostatic Water for Injection Sterile Water for Irrigation Sterile Water for Inhalation Nonmonographed Waters Drinking Water Other Nonmonographed Waters Ammonia-Free Water Carbon Dioxide-Free Water Distilled Water Freshly Distilled Water Deionized Water Deionized Distilled Water Filtered Water High-Purity Water Deaerated Water Oxygen-Free Water Water For Bacterial Endotoxins Test ....To be continued.... .

Periodic review and requalification: Periodic review and requalification shall be carried out to ensure the Utilities and equipment should be maintained in a qualified state throughout the life-cycle of the utility or equipment. Utilities and equipment should be maintained in a qualified state throughout the life-cycle of the utility or equipment. Utilities and equipment should be reviewed periodically, to confirm that they remain in a qualified state or to determine the need for requalification. Where the need for requalification is identified, this should be performed. Principles of risk management should be applied in the review and requalification and the possible impact of small changes over a period of time should further be considered (such as, through change control). Principles of risk management may include factors such as calibration, verification, maintenance data and other information. The qualification status and periodic requalification due dates should be documented, for example, in a qualification matrix, schedule or plan. In case a utility or equipment in use is identified that has not been subjected to qualification, a qualification protocol should be prepared where elements of URS, design specifications, operation and performance are verified for acceptability. The outcome of this qualification should be recorded in a report.

User Requirements Specification (URS), An authorized document that defines the requirements for use of the system, equipment or utility in its intended production environment. The User Requirements Specification document contains requirements from multidisciplinary sources and supports design, commissioning and qualification activities, operations, and maintenance. URS documentation should be prepared for, but not limited to, utilities and equipment, as appropriate. URS should be used at later stages in qualification, to verify that the purchased and supplied utility or equipment is in accordance with the user’s needs. For the Preparation of URS, Critical Quality Attributes (CQAs) and Critical Process Parameters (CPPs) are key inputs into user requirements specifications which are required to support the Quality Risk Management based Commissioning and Qualification process and are identified prior to User Requirement Specification generation. User requirements specifications documents can be written around a platform to address the requirements of a multi-purpose operation. User requirements specifications are living documents that are updated as requirements change during any phase of a project or as additional risk controls are identified. The user requirements specification document should not contain the content of engineering specifications and standards, the means by which user requirements are met, or contain contractual contract requirements. User shall define their requirements in this document (URS) by considering the following points, (Not limited to); Requirement from vendor, Packing and Transportation Quality Agreement Documentations e.g. Design Qualification (DQ), Factory Acceptance Test (FAT), Installation Qualification (IQ), Operational Qualification(OQ), User Manual / Maintenance Manual, Preventive Maintenance Reomandetion, Spare Part List, Certificate of Bought out items for Calibration, Material of construction (MOC) etc. wherever applicable. Support in Factory Acceptance Test (FAT), Installation Qualification (IQ) and Operational Qualification(OQ). After Installation Service Operational Requirement, What is the input and what is the output requirement Automation or Manual Cleanability (wherever applicable.) Engineering Requirement, Functional Specification / Requirement, Utility requirements e.g. Electricity, Water, Steam, Light, Compressed Air, Gases (Nitrogen, Oxygen etc.), HVAC, Computer System etc. Control Strategic Requirement, Password protection Security Level Safety (Operator and Equipment) Specific Requirement, The specific requirement like; if any equipment has interconnectivity with other equipment which may be existing equipment or need to purchase from other vendors References, in this section, User shall mention preferable Make and Models which are available in the market and fulfill the user's requirement Dear readers; I am Inviting you to become a part of the DPT Family (Dynamic Pharma Team).and use the Forum for knowledge sharing... To update yourself; regularly visit our website: www.pharmaceuticalguideline.com and become a member (it's FREE) by clicking the Login button at the top right corner of the webpage, also subscribe to our newsletter, Like our website, follow us on Facebook (https://www.facebook.com/pharmaceuticalguideline) Instagram (https://www.instagram.com/pharmaceuticalguideline/) LinkedIn (https://www.linkedin.com/company/pharmaceuticalguideline) Twitter (https://twitter.com/pharma_guidance) Telegram,

Principle In principle, premises, systems, utilities and equipment should be appropriately designed, installed, qualified, operated, cleaned and maintained, to suit their intended purpose. Quality management systems should be in place to ensure that these remain in a qualified state throughout their life-cycle. Products should be produced and controlled using qualified equipment and instruments. Manufacturers who may use an alternative verification framework to achieve qualification should ensure the qualification expectations within these guidelines are satisfied. Basic Flow of the Qualification Change control / Change Management, User Requirements Specification (URS), Design Qualification (DQ), Factory Acceptance Test (FAT), Site Acceptance Test (SAT), Installation Qualification (IQ), Operational Qualification (OQ), Performance Qualification (PQ). Note: The remainder of the text in these guidelines will refer to utilities and equipment as examples, even though the principles may be applicable to others such as premises and systems. Change control / Change Management, change control/change management. A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a qualified status of equipment/utility; The intent is to determine the need for action that would ensure the equipment/utility is maintained in a qualified state. User Requirements Specification (URS), An authorized document that defines the requirements for use of the system, equipment or utility in its intended production environment. Design Qualification (DQ), Documented evidence that, for example, the premises, supporting systems, utilities and equipment have been designed for their intended purposes and in accordance with the requirements of good manufacturing practices. Factory Acceptance Test (FAT), A test conducted, usually at the vendor’s premises, to verify that the system, equipment or utility, as assembled or partially assembled, meets approved specifications. Site Acceptance Test (SAT), A test conducted at the manufacturer’s site of use, to verify that the system, equipment or utility, as assembled or partially assembled, meets approved specifications. Installation Qualification (IQ), The performance of tests to ensure that the installations (such as machines, measuring devices, utilities and manufacturing areas) used in a manufacturing process are appropriately selected and correctly installed. Operational Qualification (OQ), Documented verification that the system or subsystem performs as intended over all anticipated operating ranges. Performance Qualification (PQ). Documented verification that the equipment or system operates consistently and gives reproducibility within defined specifications and parameters, for prolonged periods. The scope and extent of qualification and requalification should be determined based on the principles of impact assessment and risk management. Qualification should be executed by trained personnel. Training records should be maintained. Where appropriate, new premises, systems, utilities and equipment should be subjected to all stages of qualification. This includes the preparation of user requirements specification (URS), design qualification (DQ), installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ). Where it is decided that not all stages of qualification are required, justification should be provided. Qualification should be performed in accordance with predetermined and approved qualification protocols. The protocol should specify the prerequisites and test details, including acceptance criteria. The results of the qualification should be recorded and reflected in qualification reports.

In this article, we will discuss a practical approach to prepare the Site Master File (SMF) for the Pharmaceutical Industry. We have to understand that The SMF is the document which explains your organization; it creates the image of the organization, So it should be self-explanatory as in most of the case you are not present to explain the SMF. Do you believe that the SMF is creating the first impression of your organization before visiting your Site… After discussing with various regulatory authorities and Customers to whom the organization is submitting their SMF; I have noticed their concern related to SMF and I am summarizing the same here. What is SMF? Why SMF is Require? Who should prepare the SMF? When the SMF should be prepared? For Whom the SMF should be prepared? How to prepare the SMF? What is SMF? The site master file (SMF) is a level 1 document as I have explained in my previous article. The site master file (SMF) is prepared by the pharmaceutical manufacturer and should contain specific information about the quality management policies and activities of the site, the production and/or quality control of pharmaceutical manufacturing operations carried out at the named site, and any closely integrated operations at adjacent and nearby buildings. if only part of a pharmaceutical operation is carried out on the site, the SMF need only describe those operations, e.g. analysis, packaging, etc. Why SMF is Require? - SMF is a regulatory requirement and it belongs to Quality System - For business purpose; it is representative of the organization Who should prepare the SMF? The SMF should be prepared by the organization that is involved in manufacturing operations such as production, packaging and labeling, testing, relabelling, and repackaging of all types of medicinal products. It should be also prepared by blood and tissue establishments and manufacturers of active pharmaceutical ingredients (APIs). When the SMF should be prepared? Initially at the time of the establishment of the organization, as and when change in the content of the SMF, or any revision in the Guideline. For Whom the SMF should be prepared? Represent the organization to Regulatory Authority and customer How to prepare the SMF? The perfect guidance is provided in three major guidelines of pharmaceutical regulatory as follows; EudraLex; Volume 4; Explanatory Notes on the preparation of a Site Master File (Year:2011) PIC/S; PE 008-4; EXPLANATORY NOTES FOR PHARMACEUTICAL MANUFACTURERS ON THE PREPARATION OF A SITE MASTER FILE (Year:2011) WHO; Technical Report Series, No.961; Annex 14, WHO guidelines for drafting a site master file (Year:2011) Above all three guidelines are the same, so it is easy to prepare the SMF without confusion. General considerations: The Site Master File is prepared by the pharmaceutical manufacturer and should contain specific information about the quality management policies and activities of the site, the production and/or quality control of pharmaceutical manufacturing operations carried out at the named site, and any closely integrated operations at adjacent and nearby buildings. If only part of a pharmaceutical operation is carried out on the site, a Site Master File need only describe those operations, e.g. analysis, packaging, etc. When submitted to a regulatory authority, the Site Master File should provide clear information on the manufacturer’s GMP-related activities that can be useful in the general supervision and in the efficient planning and undertaking of GMP inspections. A Site Master File should contain adequate information but, as far as possible, not exceed 25-30 pages plus appendices. Simple plans outline drawings or schematic layouts are preferred instead of narratives. The Site Master File, including appendices, should be readable when printed on A4 paper sheets. The Site Master File should be a part of documentation belonging to the quality management system of the manufacturer and kept updated accordingly. The Site Master File should have an edition number, the date it becomes effective, and the date by which it has to be reviewed. It should be subject to regular review to ensure that it is up to date and representative of current activities. Each Appendix (Annex) can have an individual effective date, allowing for independent updating. The Site Master File is useful to the regulatory authority in planning and conducting the GMP inspections. CONTENT OF SITE MASTER FILE 1. General information on the manufacturer 1.1 Contact information on the manufacturer — name and official address of the manufacturer; — names and street addresses of the site, buildings, and production units located on the site; — contact information of the manufacturer including the 24-hour telephone number of the contact personnel in the case of product defects or recalls; and — identification number of the site as e.g. global positioning system (GPS) details, D-U-N-S (Data Universal Numbering System) number (a unique identification number provided by Dun & Bradstreet) of the site or any other geographical location system. 1.2 Authorized pharmaceutical manufacturing activities of the site — copy of the valid manufacturing authorization issued by the relevant competent authority in Annex 1; or when applicable, reference to the EudraGMP database. If the competent authority does not issue manufacturing authorizations, this should be stated; — brief description of manufacture, import, export, distribution, and other activities as authorized by the relevant competent authorities including foreign authorities with authorized dosage forms/activities, respectively; where not covered by the manufacturing authorization; — type of products currently manufactured on-site (list in Annex 2) where not covered by Annex 1 or the EudraGMP database; and — list of GMP inspections of the site within the last five years; including dates and name/country of the competent authority having performed the inspection. A copy of the current GMP certificate (Annex 3) or reference to the EudraGMP database should be included, if available. 1.3 Any other manufacturing activities carried out on the site — description of non-pharmaceutical activities on-site, if any. 2. Quality management 2.1 The quality management system of the manufacturer — brief description of the quality management systems run by the company and reference to the standards used; — responsibilities related to the maintaining of the quality system including senior management; and — information on activities for which the site is accredited and certified, including dates and contents of accreditations, and names of accrediting bodies. 2.2 Release procedure of finished products — detailed description of qualification requirements (education and work experience) of the authorized person(s)/qualified person(s) responsible for batch certification and releasing procedures; — general description of batch certification and releasing procedure; — role of the authorized person/qualified person in quarantine and release of finished products and in the assessment of compliance with the marketing authorization; — the arrangements between authorized persons/qualified persons when several authorized persons/qualified persons are involved; and — statement on whether the control strategy employs process analytical technology (PAT) and/or real-time release or parametric release. 2.3 Management of suppliers and contractors — a brief summary of the establishment/knowledge of the supply chain and the external audit program; — a brief description of the qualification system of contractors, manufacturers of APIs, and other critical materials suppliers; — measures taken to ensure that products manufactured are compliant with transmitting animal spongiform encephalopathy (TSE) guidance; — measures adopted where substandard/spurious/falsely-labeled/falsified/counterfeit medical products, bulk products (i.e. unpacked tablets), APIs or excipients are suspected or identified; — use of outside scientific, analytical, or other technical assistance in relation to manufacture and analysis; — list of contract manufacturers and laboratories including the addresses and contact information and flowcharts of supply chains for outsourced manufacturing and QC activities, e.g. sterilization of primary packaging material for aseptic processes, testing of starting raw materials, etc., should be presented in Annex 4; and — brief overview of the responsibility-sharing between the contract giver and acceptor with respect to compliance with the marketing authorization (where not included under 2.2). 2.4 Quality risk management — brief description of quality risk management (QRM) methodologies used by the manufacturer; and — scope and focus of QRM including a brief description of any activities which are performed at the corporate level, and those which are performed locally. Any application of the QRM system to assess continuity of supply should be mentioned. 2.5 Product quality reviews — brief description of methodologies used. 3. Personnel — organization chart showing the arrangements for quality management, production, and quality control positions/titles in Annex 5, including senior management and authorized person(s)/qualified person(s); and — number of employees engaged in the quality management, production, quality control, storage, and distribution, respectively. 4. Premises and equipment 4.1 Premises — short description of plant: the size of the site and list of buildings. If the products for different markets, i.e. for the local country or regional economic areas, take place in different buildings on the site, the buildings should be listed with destined markets identified (if not identified under 1.1); — simple plan or description of manufacturing areas with an indication of scale (architectural or engineering drawings are not required); — layouts and flowcharts of the production areas (in Annex 6) showing the room classification and pressure differentials between adjoining areas and indicating the production activities (i.e. compounding, filling, storage, packaging, etc.) in the rooms; — layouts of warehouses and storage areas, with special areas for the storage and handling of highly toxic, hazardous, and sensitizing materials indicated, if applicable; and — brief description of specific storage conditions if applicable, but not indicated on the layouts. 4.1.1 Brief description of heating, ventilation, and air-conditioning (HVAC) systems — principles for defining the air supply, temperature, humidity, pressure differentials and air-change rates, the policy of air recirculation (%). 4.1.2 Brief description of water systems — quality references of water produced; and — schematic drawings of the systems in Annex 7. 4.1.3 Brief description of other relevant utilities such as steam, compressed air, nitrogen, etc. 4.2 Equipment 4.2.1 Listing of major production and control laboratory equipment with critical pieces of equipment identified should be provided in Annex 8. 4.2.2 Cleaning and sanitation — brief description of cleaning and sanitation methods of product contact surfaces (i.e. manual cleaning, automatic clean-in-place, etc.). 4.2.3 Good manufacturing practices critical computerized systems — description of GMP critical computerized systems (excluding equipment-specific programmable logic controllers (PLCs)). 5. Documentation — description of documentation system (i.e. electronic, manual); and — when documents and records are stored or archived off-site (including pharmacovigilance data, when applicable): list of types of documents/records; name and address of storage site; and an estimate of the time required to retrieve documents from the off-site archive. 6. Production 6.1 Type of products References to Annex 1 or 2 can be made. — type of products manufactured including: • list of dosage forms of both human and veterinary products which are manufactured on the site • list of dosage forms of investigational medicinal products (IMP) manufactured for any clinical trials on the site, and when different from the commercial manufacturing, information on production areas and personnel; — toxic or hazardous substances handled (e.g. with high pharmacological activity and/or with sensitizing properties); — product types manufactured in a dedicated facility or on a campaign basis, if applicable; and — PAT applications, if applicable: a general statement of the relevant technology; and associated computerized systems. 6.2 Process validation — brief description of general policy for process validation; and — policy for reprocessing or reworking. 6.3 Material management and warehousing — arrangements for the handling of starting materials, packaging materials, bulk and finished products including sampling, quarantine, release, and storage; and — arrangements for the handling of rejected materials and products. 7. Quality control — description of the QC activities carried out on the site in terms of physical, chemical and microbiological, and biological testing. 8. Distribution, complaints, product defects, and recalls 8.1 Distribution (to the part under the responsibility of the manufacturer) — types (wholesale licence holders, manufacturing licence holders, etc.) and locations (countries or regional economic areas) of the companies to which the products are shipped from the site; — description of the system used to verify that each customer/recipient is legally entitled to receive medicinal products from the manufacturer; — brief description of the system to ensure appropriate environmental conditions during transit, e.g. temperature monitoring/control; — arrangements for product distribution and methods by which product traceability is maintained; and — measures are taken to prevent manufacturers’ products entering into the illegal supply chain. 8.2 Complaints, product defects, and recalls — brief description of the system for handling complaints, product defects, and recalls. 9. Self-inspections — short description of the self-inspection system with a focus on criteria used for selection of the areas to be covered during planned inspections, practical arrangements, and follow-up activities. Annexes to submission of a site master file Annex 1 Copy of valid manufacturing authorization Annex 2 List of dosage forms manufactured including the International Nonproprietary Names (INN) or common name (as available) of APIs used Annex 3 Copy of valid GMP certificate Annex 4 List of contract manufacturers and laboratories including the addresses and contact information, and flowcharts of the supply chains for these outsourced activities Annex 5 Organizational charts Annex 6 Layouts of production areas including material and personnel flows, general flowcharts of manufacturing processes of each product type (dosage form) Annex 7 Schematic drawings of water systems Annex 8 List of major production and laboratory equipment If you requireExample SMF; I will provide Sample SMF for OSD and the Injectable site. you can write in the comment box for the same. Dear readers; I am Inviting you to become a part of the DPT Family (Dynamic Pharma Team. To update yourself; regularly visit our website: www.pharmaceuticalguideline.com and become a member (it's FREE) by clicking the Login button at the top right corner of the webpage, also subscribe to our newsletter, Like our website, follow us on Facebook (https://www.facebook.com/pharmaceuticalguideline) Instagram (https://www.instagram.com/pharmaceuticalguideline/) LinkedIn (https://www.linkedin.com/company/pharmaceuticalguideline) Twitter (https://twitter.com/pharma_guidance) Telegram, Download Telegram App on your Mobile and use @pharmaceuticalguideline for search. Your like is inspiring us to prepare the articles...

Performance Qualification: Documented verification that the equipment or system operates consistently and gives reproducibility within defined specifications and parameters, for prolonged periods. PQ should normally follow the successful completion of IQ and OQ. In some cases, it may be appropriate to perform PQ in conjunction with OQ or process validation. This should be justified and documented in the validation master plan (or qualification protocol). The SOP for the Operation, Cleaning, and maintenance of Equipment, system, Utility etc. shall be approved before Performance Qualification. The Performance Qualification study depends on the Equipment, system, or Utility; e.g. The PQ study for Water System shall be carried out in three-phase to check the variability in performance due to the different seasons during the year. PQ should include, but is not limited to, the following: tests using production materials, qualified substitutes or simulated products are proven to have equivalent behavior under operating conditions, with batch sizes where appropriate; tests covering the intended operating range. Utilities and equipment should consistently perform in accordance with their design specifications and URS. The performance should be verified in accordance with a PQ protocol. There should be records for the PQ (e.g. a PQ report), to indicate satisfactory performance over a predefined period of time. Manufacturers should justify the period over which PQ is done.

Operational Qualification.: Documented verification that the system or subsystem performs as intended over all anticipated operating ranges. Requirements and procedures for operation (or use), calibration, maintenance and cleaning should be prepared before OQ and approved prior to PQ. Utilities and equipment should operate correctly and their operation should be verified in accordance with an OQ protocol. OQ normally follows IQ but, depending on the complexity of the utility or equipment, it may be performed as a combined installation/operation qualification (IOQ). This should be justified and documented in the validation master plan (or qualification protocol). OQ should include, but is not limited to, the following: tests that have been developed from the knowledge of processes, systems and equipment, to ensure the utility or equipment is operating as designed; tests over the operating limits. Training of operators for the utilities and equipment should be provided and training records maintained. Calibration, cleaning, maintenance, training and related tests and results should be verified to be acceptable. Deviations and non-conformances observed should be recorded, investigated and corrected or justified. The results for the verification of operation should be documented in the OQ report. The outcome of the OQ should be recorded in the conclusion of the report, normally before PQ is started.