Documentation relating to product development,sop's,cleaning methods,quality control documentation
PREPARED BYS.SUSENA,SSJ COLLEGE OF PHARMACY,M.PHARMACY(P.ANALYSIS&QA)DOCUMENTATION RELATING TO PRODUCTDEVELOPMENT,STANDARD OPERATING PROCEDURES,CLEANING METHODS,QUALITY CONTROL DOCUMENTATION
DEFINITIONDocumentation is a process that involves the systematic interaction of people, eventsand documents to create the records of the organization / corporation. There is saying in thepharmaceutical industry- ‘if it hasn’t been documented, then it hasn’t happened!’ It acts as aproactive vehicle for communication.Document :- A piece of written, typed, printed/electronic matter that providesinformation/evidence.PRINCIPLES Good documentation constitutes an essential part of the quality assurance system. Clearly written documentation prevents errors from spoken communication and permitstracing of batch history. “Your documentation is an advertisement for your work”.OBJECTIVES To define all materials specifications. To ensure all personal of manufacture and control department know what to do and when todo. To provide information during investigation, if a batch is suspected to have defect(s).
ESSENTIAL CHARACTERISTICS The document directing the manufacturing event fulfills current regulatorycommitments. The directive document is appropriate for the task to be performed. The data is accurate and legible. The data is authentic. The data collected fulfills specifications. The original data and the original documents (manufacturing record) areretrievable for review or audit.REQUIREMENTS FOR A GOOD DOCUMENTATIONFor effective use of documents, they should be designed and preparedwith utmost care. Each document shall: Have a clear title. Have an identification number. Be approved by authorized person. Have the date of issue.
INCEPTIONDESIGNPREPARATIONAPPROVAL CREATION OF NEW DOC.AUTHORIZATIONCOMMUNICATIONTRAININGIMPLEMENTATIONPERIODIC REVIEWREVISIONREVISED OBSOLESCENCEDOCUMENTWITHDRAWALARCHIVING
TYPES OF DOCUMENTS : There are three types of Documents -1. Commitment Documents: Relationship between industry and the regulatoryauthorities.Ex: New Drug Applications (NDAs), Drug Master Files (DMFs) etc. These present corporate goals, expectations and standard of practice. Describes what to do . . . . . . ??? It organizes the work in a manner that assures efficient and effective work flow. Written to lead and guide the work and workers. To be used as active documents that are consulted and followed routinely. Deviations from regulatory submissions can have significant impact on productquality. Any deviation must be documented and managed.
New Drug Applications (NDAs):- The New Drug Application (NDA) is the vehiclein the United States through which drug sponsors formally propose that the FDAapprove a new pharmaceutical for sale and marketing. The goals of the NDA areto provide enough information to permit FDA reviewers to establish the following: Is the drug safe and effective in its proposed use(s) Is the drug‟s proposed labeling (package insert) appropriate Are the methods used in manufacturing (Good Manufacturing Practice, GMP)the drug and the controls used to maintain the drug‟s quality adequate topreserve the drug‟s identity, strength, quality, and purity? Drug Master Files (DMFs):- Drug Master File or DMF is a document prepared bya pharmaceutical manufacturer and submitted solely at its discretion to theappropriate regulatory authority in the intended drug market. However, thedocument provides the regulatory authority with confidential, detailed informationabout facilities, processes, or articles used in themanufacturing, processing, packaging, and storing of one or more human drugs.Drug Master File (DMF) is a document containing complete information onan Active Pharmaceutical Ingredient (API) or finished drug dosage form. TheDMF contains factual and complete information on a drug product‟schemistry, manufacture, stability, purity, impurity profile, packaging, and thecGMP status of any human drug product.
2. Directive Documents: Relationship between the Management and Employees.Ex: Specifications, Standard Test Processes (STPs), Standard OperatingProcedures (SOPs), Medicinal Product Records (MPRs) etc. They establish the standards for resources, processing, products & qualitysystem. It facilitates the development, production, testing and distribution of a productin a defined manner. Describe how to do . . . . . . ??? There are several types of directive documents which are determined by thespecific, functional purpose of the document in the document system. Specifications:- A document specification contains several parts: a descriptionof the audience(s) for the document, a detailed outline giving the structureand contents of the document, and a work plan showing who is responsiblefor each part of the document and what the deadlines are for completing eachtask.
There are three purposes for document specifications: Economy of Effort: First, document specifications are used to help you reducethe amount you have to write.E.g.- When you want to write a major report, first you prepare a draft for it, thenrevise this draft & then make a document out of it.You can often reduce this work load if you write a detailed documentspecification instead. A document specification is much easier tocreate, change, revise, and add to than a draft is. Work planning: The second major function of a document specification is workplanning. This can mean either budgeting your own time, or distributing thework among many people. You should bear three things in mind in dividing thework: even work load, respective areas of expertise, and getting things done inorder that you need them. Writing Organization: The third major function is organization of the report itself.
Standard Operating Procedures (SOPs):- A Standard Operating Procedure(SOP) is a set of written instructions that guide employees in their areas ofresponsibility. The development and use of SOPs are an integral part of asuccessful quality system as it provides individuals with the information toperform a job properly, and facilitates consistency in the quality and integrityof a product or end-result. The term “SOP” may not always be appropriateand terms such as protocols, instructions, worksheets, and laboratoryoperating procedures may also be used.3. Record Documents : Relationship between the Employees and the Work theyperform.Ex: Protocols, Batch Production Records (BPRs), Log Books, Calibration Recordsetc. Protocol:- Protocols are written records clearly defining the objectives andmethods that will be used for the validation programs. An important part ofthe protocol is the description of the testing method including who will testthe system, how they will test it and what data is to be collected andreported.Computerized system protocols often include three distinct stages:Installation Qualification(IQ), Operational Qualification (OQ), andPerformance Qualification (PQ).
STANDARD OPERATING PROCEDURES(SOP)INTRODUCTIONSOPs document a process in the form of „who‟ „what‟ „when‟ and ‟how‟. Theydefine how a task is to be performed, to achieve a specified outcome and standardizethe way it is to be performed so as to minimize variation.BENEFITS SOPs are used as checklists by inspectors when auditing procedure. Ultimately the benefits of valid SOP are reduce work effort, along with improveddata comparability and legal defensibility. A collection of well written SOPs and supporting documents can therefore act ascritical foundation for process improvement and organization efficiency.TYPES1. Administrative Type:- It covers permissions and access control to specific dataor areas of a facility. Administrative SOPs can be written for wide variety ofactivities, for example reviewing documentation such as contracts, QA projectplans and quality management plans; inspecting (auditing); determiningorganizational training needs.
2. Technical Type:- The second type is the technical type, such as operation of thetablet compression machine, i.e. operations being performed by technicians inthe production area. Sometimes companies also use more specific types offunctional document called work instruction to provide details on how one personaccomplishes his or her job. A work instruction in any case is always related totechnical procedures rather than administrative ones.CONTENTS OF SOPSAn SOP includes:- A list of materials and components required for processing. Full description of reagents, components or handling that must be performedbefore process initiation. A list of equipment required and its relevant features that may includecapacities, precision, and compatibilities and limitations. A stepwise description of the processing event. Process control parameters with testing limits or acceptance criteria.
LIFE CYCLE OF SOPsCREATE/EDITREVIEWAPPROVEPUBLISHDISTRIBUTEARCHIVE
GUIDE FORMAT FOR SOPThis SOP is for oral liquid filling machine._______________________________________________________Name of Company _______________________________________Address ________________________________________________SOP FOR CLEANING OF LIQUID ORAL FILLING MACHINESOP NO. …………………. Effective from ……………….. (Date)________________________________________________________________________Prepared by checked by ResponsibilitySection Supervisor________________________________________________________________________Approved byIn-charge In-chargeProduction Quality control________________________________________________________________________1. Drain out holding tank of left overs, if any.2. Fill the holding tank with water up to a height of ________ cm washing the internal surfaces and switch on filling machine. Run the machine till the water is removed fromholding tank (as much as is possible).3. Now open the drain valve of holding tank.4. Disassemble nozzles and washer.5. Remove tubing.6. Clean all parts with jet of water for _______ minutes.7. Soak parts and flexible tubings in antiseptic solution for 30 min. (0.5% cetrimide solution can be used for this purpose).8. Wash these parts & tubings in running water.9. Soak these in previously boiled & hot purified water.10. If steam is available subject the parts to live steam. If steam is not available, use 70% Isopropyl alcohol and allow to dry.11. Clean the flexible tubing in the similar way.12. Cover ends of clean tubing with polyethylene sheets.13. Clean the holding tank with previously boiled & hot purified water. If steam is not available, treat the holding tank with sodium hypochlorite solution (0.1%).14. Assemble the equipment.15. Label the equipment with status label e.g. “Ready for use”.__________________________________________________________________________
SOP DOCUMENTATIONEach organization should develop a numbering system tosystematically identify and label their SOPs, and the document control shouldbe described in its Quality Management Plan. Generally, each page of an SOPshould have control documentation notation, similar to that illustrated below. Ashort title and identification (ID) number can serve as a reference designation.The revision number and date are very useful in identifying the SOP in usewhen reviewing historical data and is critical when the need for evidentiaryrecords is involved and when the activity is being reviewed. When the numberof pages is indicated, the user can quickly check if the SOP is complete.Generally this type of document control notation is located in the upper right-hand corner of each document page following the title page.Short Title/ID #Rev. #:Date:Page 1 of
CLEANING METHODS INTRODUCTIONCleaning is one of the major and critical activities in pharmaceuticaloperation. It is enough to say that clean environment and clean operations is theheart of pharmaceutical activities.The four basic requirements of cGMP are identity, safety, strength andpurity. The concept of purity and safety are directly related to the cleaningoperations.There are different levels or degrees of cleanliness required inpharmaceutical operations and naturally the specification of each of the cleaningwill differ substantially.OBJECTIVES The major objective of cleaning methods is to avoid contamination of thepharmaceutical products or that contamination is reduced to an acceptable level. To confirm a reliable cleaning procedure so that the analytical monitoring may beomitted or reduced to a minimum in the routine phase.
OUTLINE OF A CLEANING METHODDesigning of a cleaning method is an important task. This process ofdesigning includes What is being cleaned? e.g. Equipment, Facilities, Vessels and containers What are the contaminants? e g. Micro-organisms, Endotoxins, Dust and fibres What is the level of cleanliness expected and what is the acceptance criteria? Which cleaning agents to be used and at what concentration? Who is going to do the cleaning? Who is going to supervise? What record will be maintained?Once the data related to above points is collected then the requiredcleaning method may be adopted.
DIFFERENT METHODS OF CLEANING Manual cleaning procedures Semi-automated cleaning procedures Fully automated cleaning proceduresManual cleaning procedures are operator dependent. It however, does notmean that they are not effective, if these are carried out by properly trainedoperators, they could be superior to automated methods.But in the semi-automated and automated cleaning procedures, there isreduced operator involvement. However, this may not always be advantageous asthe operator during manual cleaning can inspect the equipment at every step andmay repeat the step if required.CLEANING ARRAY Equipment disassembly Prewash Wash Initial rinses Final rinse Reassembly
DOCUMENTATION FOR CLEANINGThe following aspects to be considered during the documentation of acleaning procedure are:- Detailed cleaning procedure(s) are to be documented in SOPs.• When more complex cleaning procedures are required, it is important todocument the critical cleaning steps.• Other factors such as history of cleaning, residue levels found aftercleaning, and variability of test results may also dictate the amount ofdocumentation required.• The cleaning record should be signed by the operator who performed thecleaning and by the person responsible for Production and should be reviewedby Quality Assurance.
QUALITY CONTROL DOCUMENTATION INTRODUCTIONGood documentation is an essential part of QA/QC system. It defines asystem of information and control, so that misinterpretation or error in oralcommunications is minimized.OBJECTIVES To define the specifications of all materials. To prevent unambiguous procedures to be followed. To allow tracing of the batch history of any product.TYPES OF QC DOCUMENTS1. Quality manual2. Specifications and testing procedures For starting and packaging materials For intermediate and bulk products For finished products For containers and closures3. SOP‟s and records
1. Quality ManualA quality manual is a documented quality system procedure intended for theoverall planning and administration of activities which impacts quality within anorganization. A quality manual should cover all the applicable elements of thequality system standards required for an organization.Purpose of quality manual Communicating the organization quality policy, procedures and requirements Describing and implementing effective quality system Providing the documented bases for auditing the quality systemQuality policy - It is a statement made by the head of the organization on behalfof the organization, stating the organizations views and concern about quality.
2. Specifications and Testing ProceduresSpecification - A document describing in detail the requirements with which theproduct obtained during manufacture have to conform. Each specification should be approved and maintained by the quality controlunit Periodic revisions of the specifications may be necessary to comply with neweditions of the national pharmacopoeia or other official pharma compendia• Testing procedures described in documents should be validated in context ofavailable facilities and equipment before they are adopted for routine testing For starting and packaging materials The designated name and internal code reference; The reference, if any, to a pharmacopoeial monograph; and Qualitative and quantitative requirements with acceptance limits For intermediate and bulk productsSpecifications for intermediate and bulk products should beavailable if these are purchased or dispatched, or if data obtained fromintermediate products are used in the evaluation of the finished product.
For finished products- The designated name of the product and the code reference whereapplicable;- The designated name(s) of the active ingredient(s)- A description of the dosage form and package details;- The qualitative and quantitative requirements, with acceptance limits;- The storage conditions and precautions, where applicable; and- The shelf-life. For containers and closuresAll containers and closures intended for use shall comply with thepharmacopeial requirements. Suitable validated test methods, samplesizes, specifications, cleaning procedure and sterilization procedure, whereever indicated, should be followed strictly to ensure that these are notreactive, additive, and adsorptive or leach and neither effects the quality orpurity of the drugs.
3. Standard Operating Procedures (SOPs) and RecordsThere should be standard operating procedures for the following:IPQC during packagingChange control systemComplaint handling and Product recallProduct recallStability testing
REFERENCES1. DOCUMENTATION RELATING TO PRODUCT DEVELOPMENT Pg: 166 & 247 of Q.A Manual by D.H Shah Pg: 206; 363 & 388 of How to practice GMP‟s by P.P Sharma Pg: 339 of cGMP for Pharmaceuticals by Manohar A. Potdar www.robelle.com/library/papers/step/process.doc2. STANDARD OPERATING PROCEDURES Pg: 255-259 of How to practice GMP‟s by P.P Sharma SOP Guidelines by D.H Shah Pg: 377 of cGMP for Pharmaceuticals by Manohar A. Potdar http://www.epa.gov/QUALITY/qs-docs/g6-final.pdf http://www.mtnstopshiv.org/sites/default/files/attachments/SourceDocSOPv2.pdf3. CLEANING METHODS Pg: 453 of cGMP for Pharmaceuticals by Manohar A. Potdar Pg: 79 of How to practice GMP‟s by P.P Sharma SOP Guidelines by D.H Shah Pg: 70 of Q.A Manual by D.H Shah http://www.irjponline.com/admin/php/uploads/1205_pdf.pdf
4. QUALITY CONTROL DOCUMENTATION Pg: 230 of cGMP for Pharmaceuticals by Manohar A. Potdar Pg: 286 of How to practice GMP‟s by P.P Sharma http://www.alspi.com/quality.pdf http://microcontacts.com/pdf/quality_manual.pdf http://www.optekinc.com/pdf/QualityManual.pdf